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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT02997228
Other study ID # NCI-2016-01961
Secondary ID NCI-2016-01961NR
Status Recruiting
Phase Phase 3
First received
Last updated
Start date January 19, 2018
Est. completion date November 30, 2024

Study information

Verified date March 2024
Source National Cancer Institute (NCI)
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This phase III trial studies how well combination chemotherapy, bevacizumab, and/or atezolizumab work in treating patients with deficient deoxyribonucleic acid (DNA) mismatch repair colorectal cancer that has spread from where it first started (primary site) to other places in the body (metastatic). Chemotherapy drugs, such as fluorouracil, oxaliplatin, and leucovorin calcium, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Bevacizumab may stop or slow colorectal cancer by blocking the growth of new blood vessels necessary for tumor growth. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving combination chemotherapy, bevacizumab, and atezolizumab may work better in treating patients with colorectal cancer.


Description:

PRIMARY OBJECTIVE: I. To determine the efficacy, based on progression-free survival (PFS), of fluorouracil, oxaliplatin, and leucovorin calcium (modified [m]FOLFOX6)/bevacizumab plus atezolizumab (combination) as compared to single agent atezolizumab. SECONDARY OBJECTIVES: I. To compare the overall survival. II. To compare the objective response rates (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. III. To determine the safety profiles of single agent atezolizumab and the combination of mFOLFOX6/bevacizumab/atezolizumab in patients with mismatch-repair deficient (dMMR)/microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC). IV. To determine the duration of response. V. To determine the duration of stable disease. VI. To determine the rate of progression-free survival (PFS) at 12 months. VII. To evaluate the disease control rate (complete response [CR] + partial response [PR] + stable disease [SD]) at 12 months. TRANSLATIONAL OBJECTIVE: I. To bank tissue and blood samples for other future correlative studies from patients enrolled on the study. OUTLINE: Patients are randomized to 1 of 3 arms. ARM I: Patients receive bevacizumab intravenously (IV) over 30-90 minutes on day 1, oxaliplatin IV over 2 hours on day 1 of cycles 1-10, leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV over 46-48 hours on days 1 and 2. Treatment with oxaliplatin repeats every 2 weeks for up to 10 cycles in the absence of disease progression or unacceptable toxicity. Treatment of bevacizumab, leucovorin calcium, and fluorouracil repeat every 2 weeks for up to 48 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) with or without positron emission tomography (PET) or magnetic resonance imaging (MRI) throughout the trial. Patients may also undergo collection of optional blood samples throughout the trial. (CLOSED TO ACCRUAL) ARM II: Patients receive atezolizumab IV over 30-60 minutes on day 1. Treatment repeats every 2 weeks for up to 48 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT with or without PET or MRI throughout the trial. Patients may also undergo collection of optional blood samples throughout the trial. ARM III: Patients receive atezolizumab IV over 30-60 minutes on day 1. Treatment repeats every 2 weeks for up to 48 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive bevacizumab IV over 30-90 minutes on day 1, oxaliplatin IV over 2 hours on day 1 cycles 1-10, leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV over 46-48 hours on day 1. Treatment with oxaliplatin repeats every 2 weeks for up to 10 cycles in the absence of disease progression or unacceptable toxicity. Treatment of bevacizumab, leucovorin calcium, and fluorouracil repeat every 2 weeks for up to 48 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT with or without PET or MRI throughout the trial. Patients may also undergo collection of optional blood samples throughout the trial. After completion of study treatment, patients are followed up every 8 weeks for 18 months, and then every 12 weeks for up to 5 years.


Recruitment information / eligibility

Status Recruiting
Enrollment 120
Est. completion date November 30, 2024
Est. primary completion date November 30, 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - The patient must have signed and dated an Institutional Review Board (IRB)-approved consent form that conforms to federal and institutional guidelines - Age >= 18 years - Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 - Diagnosis of metastatic adenocarcinoma of colon or rectum without previous chemotherapy or any other systemic therapy for metastatic colorectal cancer except for one cycle of FOLFOX or capecitabine and oxaliplatin (CAPOX), either with or without bevacizumab prior to enrollment. Upon enrollment, the preceding single cycle of FOLFOX or FOLFOX + bevacizumab, if the patient received one, will not count towards patients' assessments per protocol. Cycle 1 day 1 (C1D1) of atezolizumab or C1D1 of mFOLFOX6/bevacizumab + atezolizumab will correspond to the first day the patient received therapy on trial - Tumor determined to be mismatch-repair deficient (dMMR) by Clinical Laboratory Improvement Act (CLIA)-certified immunohistochemical (IHC) assay with a panel of all four IHC markers, including MLH1, MSH2, PMS2, and MSH6; alternatively, MSI-H diagnosed by polymerase chain reaction (PCR)-based assessment of microsatellite alterations (either Bethesda markers or Pentaplex panel) or by next-generation sequencing (NGS) are eligible - Documentation by PET/CT scan, CT scan, or MRI that the patient has measurable metastatic disease per RECIST 1.1 - No immediate need for surgical intervention for the primary tumor or palliative diversion/bypass - Absolute neutrophil count (ANC) must be >= 1500/mm^3 (obtained within 28 days prior randomization) - Platelet count must be >= 100,000/mm^3 (obtained within 28 days prior randomization) - Hemoglobin must be >= 8 g/dL (obtained within 28 days prior randomization) - Total bilirubin must be =< 4 x ULN (upper limit of normal) (obtained within 28 days prior randomization); and - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be =< 3 x ULN for the lab with the following exception: for patients with documented liver metastases, AST and ALT must be =< 5 x ULN (obtained within 28 days prior randomization) - Calculated creatinine clearance >= 30 mL/min (obtained within 28 days prior randomization) - A urine sample tested for proteinuria by either the dipstick method, urinalysis (UA), or a urine protein creatinine (UPC) ratio: - The dipstick method must indicate 0-1+ protein; if dipstick reading is >= 2+, a 24-hour urine must be done and it must demonstrate < 1.0 g of protein per 24 hours or a UPC ratio < 1.0 - A urine protein creatinine (UPC) ratio must be < 1.0; if the UPC ratio is >= 1.0 a 24-hour urine must be done and it must demonstrate < 1.0 g of protein per 24 hours - Urinalysis must indicate < 30 mg/dl. If urinalysis >= 30 mg/dl, a 24-hour urine must be done and it must demonstrate < 1.0 g of protein per 24 hours or a UPC ratio < 1.0 - International normalized ratio of prothrombin time (INR) and prothrombin time (PT) must be =< 1.5 x ULN for the lab within 28 days before randomization; patients who are therapeutically treated with an agent such as warfarin may participate if they are on a stable dose and no underlying abnormality in coagulation parameters exists per medical history, regardless of PT/INR results - Pregnancy test done within 28 days prior randomization must be negative (for women of childbearing potential only); pregnancy testing should be performed according to institutional standards; administration of atezolizumab or mFOLFOX6/bevacizumab/atezolizumab may have an adverse effect on pregnancy and poses a risk to the human fetus, including embryo-lethality; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately - Women of child-bearing potential and men must agree to use adequate contraception methods that result in a failure rate of < 1% per year during the treatment period (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 5 months (150 days) after the last dose of atezolizumab, 6 months after the last dose of bevacizumab, and 6 months after the last dose of mFOLFOX6; a woman is considered to be of childbearing potential if she is not postmenopausal, has not reached a postmenopausal state (>= 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus); examples of contraceptive methods with a failure rate of < 1% per year include: bilateral tubal ligation; male partner sterilization; intrauterine devices; the reliability of sexual abstinence should be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the patient; periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception; men must refrain from donating sperm during this same period Exclusion Criteria: - Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies, fluoropyrimidines, folic acid derivatives or oxaliplatin - Uncontrolled high blood pressure defined as systolic blood pressure (BP) > 150 mmHg or diastolic BP > 100 mmHg with or without anti-hypertensive medication; patients with initial BP elevations are eligible if initiation or adjustment of BP medication lowers pressure to meet entry criteria - Documented New York Heart Association (NYHA) class III or IV congestive heart failure - Serious or non-healing wound, skin ulcer, or bone fracture - History of inherited bleeding diathesis, gastrointestinal (GI) perforation, significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent arterial thrombosis or symptomatic peripheral ischemia, transient ischemic attack [TIA], cerebrovascular accident [CVA] or arterial thrombotic event), abdominal fistula, intra-abdominal abscess, or active GI bleeding (with cause not addressed) within 6 months prior to randomization, or other medical condition in the opinion of the treating oncologist that makes the risk of cardiovascular or bleeding complications with bevacizumab use unacceptably high - Other malignancies are excluded unless the patient has completed therapy for the malignancy >= 12 months prior to randomization and is considered disease-free; patients with the following cancers are eligible if diagnosed and treated within the past 12 months: in situ carcinomas or basal cell and squamous cell carcinoma of the skin - Known DPD (dihydro pyrimidine dehydrogenase) deficiency - Symptomatic peripheral sensory neuropathy >= grade 2 (Common Terminology Criteria for Adverse Events [CTCAE] version [v] 5.0) - Prior treatment with oxaliplatin chemotherapy within 6 months prior to randomization - History of grade 2 hemoptysis (defined as 2.5 mL of bright red blood per episode) within 1 month prior to screening - Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents; patients who have received prior treatment with anti-CTLA-4 may be enrolled provided the following requirements are met: - Minimum of 12 weeks from the first dose of anti-CTLA-4 and > 6 weeks from the last dose to randomization - No history of severe immune-related adverse effects (CTCAE grade 3 and 4) from anti-CTLA-4 - Treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 14 days prior to randomization; however, - Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea; or chronic daily treatment with corticosteroids with a dose of =< 10 mg/day methylprednisolone equivalent) may be enrolled - The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed - Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease; however, - Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HbsAg] test and a positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible if polymerase chain reaction (PCR) for hepatits B virus (HBV) ribonucleic acid (RNA) is negative per local guidelines - Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA per local guidelines - History or risk of autoimmune disease, including, but not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis; however, - Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible - Patients with controlled type 1 diabetes mellitus on a stable insulin regimen may be eligible - Patients with eczema, psoriasis, lichen simplex chronicus or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions: - Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations - Rash must cover less than 10% of body surface area (BSA) - Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%, alclometasone dipropionate 0.05%) - No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids) - History of idiopathic pulmonary fibrosis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or active or recently active (within 90 days of randomization) pneumonitis (including drug induced) that required systemic immunosuppressive therapy (i.e. corticosteroids, etc.). History of radiation pneumonitis in the radiation field (fibrosis) is permitted - History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins - Patients with known active tuberculosis (TB) are excluded - Severe infections within 28 days prior to randomization, including but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia - Signs or symptoms of infection within 14 days prior to randomization - Received oral or intravenous (IV) antibiotics within 14 days prior to randomization; patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible - Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to randomization or anticipation of need for a major surgical procedure during the course of the study - The administration of a live, attenuated vaccine within 28 days prior to randomization - Pregnant women are excluded from this study because atezolizumab is an agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with atezolizumab, breastfeeding should be discontinued if the mother is treated with atezolizumab; these potential risks may also apply to other agents used in this study; (Note: pregnancy testing should be performed within 28 days prior to randomization according to institutional standards for women of childbearing potential) - Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial - Patients with prior allogeneic bone marrow transplantation or prior solid organ transplantation

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Atezolizumab
Given IV
Biological:
Bevacizumab
Given IV
Procedure:
Biospecimen Collection
Undergo collection of blood samples
Computed Tomography
Undergo CT or CT/PET
Drug:
Fluorouracil
Given IV
Leucovorin
Given IV
Procedure:
Magnetic Resonance Imaging
Undergo MRI
Drug:
Oxaliplatin
Given IV
Procedure:
Positron Emission Tomography
Undergo CT/PET
Other:
Quality-of-Life Assessment
Ancillary studies
Questionnaire Administration
Ancillary studies

Locations

Country Name City State
United States Avera Cancer Institute-Aberdeen Aberdeen South Dakota
United States Cleveland Clinic Akron General Akron Ohio
United States Phoebe Putney Memorial Hospital Albany Georgia
United States Presbyterian Kaseman Hospital Albuquerque New Mexico
United States University of New Mexico Cancer Center Albuquerque New Mexico
United States Lehigh Valley Hospital-Cedar Crest Allentown Pennsylvania
United States Saint Luke's Cancer Center - Allentown Allentown Pennsylvania
United States The Don and Sybil Harrington Cancer Center Amarillo Texas
United States Mary Greeley Medical Center Ames Iowa
United States McFarland Clinic - Ames Ames Iowa
United States Community Hospital of Anaconda Anaconda Montana
United States Kaiser Permanente-Anaheim Anaheim California
United States AnMed Health Cancer Center Anderson South Carolina
United States Saint Joseph Mercy Hospital Ann Arbor Michigan
United States Langlade Hospital and Cancer Center Antigo Wisconsin
United States Ascension Saint Elizabeth Hospital Appleton Wisconsin
United States ThedaCare Regional Cancer Center Appleton Wisconsin
United States Duluth Clinic Ashland Ashland Wisconsin
United States University Cancer and Blood Center LLC Athens Georgia
United States Augusta Oncology Associates PC-D'Antignac Augusta Georgia
United States Augusta Oncology Associates PC-Wheeler Augusta Georgia
United States Augusta University Medical Center Augusta Georgia
United States Harold Alfond Center for Cancer Care Augusta Maine
United States Rocky Mountain Cancer Centers-Aurora Aurora Colorado
United States UCHealth University of Colorado Hospital Aurora Colorado
United States Kaiser Permanente-Baldwin Park Baldwin Park California
United States Saint Louis Cancer and Breast Institute-Ballwin Ballwin Missouri
United States Kaiser Permanente-Woodlawn Medical Center Baltimore Maryland
United States Eastern Maine Medical Center Bangor Maine
United States Flaget Memorial Hospital Bardstown Kentucky
United States McLaren Cancer Institute-Bay City Bay City Michigan
United States Beaufort Memorial Hospital Beaufort South Carolina
United States Baptist Hospitals of Southeast Texas Cancer Center Beaumont Texas
United States Waldo County General Hospital Belfast Maine
United States Kaiser Permanente-Bellflower Bellflower California
United States Strecker Cancer Center-Belpre Belpre Ohio
United States Sanford Joe Lueken Cancer Center Bemidji Minnesota
United States Saint Charles Health System Bend Oregon
United States Alta Bates Summit Medical Center-Herrick Campus Berkeley California
United States Lehigh Valley Hospital - Muhlenberg Bethlehem Pennsylvania
United States Saint Luke's University Hospital-Bethlehem Campus Bethlehem Pennsylvania
United States University of Iowa Healthcare Cancer Services Quad Cities Bettendorf Iowa
United States MaineHealth/SMHC Cancer Care and Blood Disorders-Biddeford Biddeford Maine
United States Billings Clinic Cancer Center Billings Montana
United States Sanford Bismarck Medical Center Bismarck North Dakota
United States McLaren Cancer Institute-Bloomfield Bloomfield Michigan
United States Illinois CancerCare-Bloomington Bloomington Illinois
United States Prisma Health Cancer Institute - Spartanburg Boiling Springs South Carolina
United States Saint Alphonsus Cancer Care Center-Boise Boise Idaho
United States Saint Luke's Cancer Institute - Boise Boise Idaho
United States McFarland Clinic - Boone Boone Iowa
United States Dana-Farber Cancer Institute Boston Massachusetts
United States Boulder Community Hospital Boulder Colorado
United States Rocky Mountain Cancer Centers-Boulder Boulder Colorado
United States Bozeman Deaconess Hospital Bozeman Montana
United States Lafayette Family Cancer Center-EMMC Brewer Maine
United States Saint Joseph Mercy Brighton Brighton Michigan
United States Trinity Health IHA Medical Group Hematology Oncology - Brighton Brighton Michigan
United States Bristol Regional Medical Center Bristol Tennessee
United States Wellmont Medical Associates-Bristol Bristol Virginia
United States Ascension Southeast Wisconsin Hospital - Elmbrook Campus Brookfield Wisconsin
United States Henry Ford Cancer Institute-Downriver Brownstown Michigan
United States Roswell Park Cancer Institute Buffalo New York
United States Kaiser Permanente-Burke Medical Center Burke Virginia
United States Minnesota Oncology - Burnsville Burnsville Minnesota
United States Saint Alphonsus Cancer Care Center-Caldwell Caldwell Idaho
United States Illinois CancerCare-Canton Canton Illinois
United States Saint Joseph Mercy Canton Canton Michigan
United States Trinity Health IHA Medical Group Hematology Oncology - Canton Canton Michigan
United States Saint Francis Medical Center Cape Girardeau Missouri
United States Illinois CancerCare-Carthage Carthage Illinois
United States Mercy Hospital Cedar Rapids Iowa
United States Oncology Associates at Mercy Medical Center Cedar Rapids Iowa
United States Dayton Physicians LLC-Miami Valley South Centerville Ohio
United States Miami Valley Hospital South Centerville Ohio
United States Centralia Oncology Clinic Centralia Illinois
United States UNC Lineberger Comprehensive Cancer Center Chapel Hill North Carolina
United States West Virginia University Charleston Division Charleston West Virginia
United States Saint Joseph Mercy Chelsea Chelsea Michigan
United States Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital Chelsea Michigan
United States Cheyenne Regional Medical Center-West Cheyenne Wyoming
United States Rush University Medical Center Chicago Illinois
United States University of Illinois Chicago Illinois
United States Adena Regional Medical Center Chillicothe Ohio
United States University of Cincinnati Cancer Center-UC Medical Center Cincinnati Ohio
United States Clackamas Radiation Oncology Center Clackamas Oregon
United States Providence Cancer Institute Clackamas Clinic Clackamas Oregon
United States Hematology Oncology Consultants-Clarkston Clarkston Michigan
United States McLaren Cancer Institute-Clarkston Clarkston Michigan
United States Newland Medical Associates-Clarkston Clarkston Michigan
United States Cleveland Clinic Cancer Center/Fairview Hospital Cleveland Ohio
United States Southeastern Medical Oncology Center-Clinton Clinton North Carolina
United States Henry Ford Macomb Hospital-Clinton Township Clinton Township Michigan
United States Medical Oncology and Hematology Associates-West Des Moines Clive Iowa
United States Mercy Cancer Center-West Lakes Clive Iowa
United States Billings Clinic-Cody Cody Wyoming
United States Kootenai Health - Coeur d'Alene Coeur d'Alene Idaho
United States Baptist Memorial Hospital and Cancer Center-Collierville Collierville Tennessee
United States Memorial Hospital North Colorado Springs Colorado
United States Penrose-Saint Francis Healthcare Colorado Springs Colorado
United States UCHealth Memorial Hospital Central Colorado Springs Colorado
United States MU Health - University Hospital/Ellis Fischel Cancer Center Columbia Missouri
United States Columbus Oncology and Hematology Associates Inc Columbus Ohio
United States Doctors Hospital Columbus Ohio
United States Grant Medical Center Columbus Ohio
United States Mount Carmel East Hospital Columbus Ohio
United States Mount Carmel Health Center West Columbus Ohio
United States Ohio State University Comprehensive Cancer Center Columbus Ohio
United States Riverside Methodist Hospital Columbus Ohio
United States The Mark H Zangmeister Center Columbus Ohio
United States John Muir Medical Center-Concord Campus Concord California
United States MD Anderson in The Woodlands Conroe Texas
United States Cookeville Regional Medical Center Cookeville Tennessee
United States Parkland Memorial Hospital Dallas Texas
United States UT Southwestern/Simmons Cancer Center-Dallas Dallas Texas
United States Danbury Hospital Danbury Connecticut
United States Carle at The Riverfront Danville Illinois
United States Miami Valley Hospital Dayton Ohio
United States Henry Ford Medical Center-Fairlane Dearborn Michigan
United States Cancer Care Specialists of Illinois - Decatur Decatur Illinois
United States Essentia Health - Deer River Clinic Deer River Minnesota
United States Delaware Health Center-Grady Cancer Center Delaware Ohio
United States Grady Memorial Hospital Delaware Ohio
United States Denver Health Medical Center Denver Colorado
United States National Jewish Health-Main Campus Denver Colorado
United States Porter Adventist Hospital Denver Colorado
United States Rocky Mountain Cancer Centers-Midtown Denver Colorado
United States Rocky Mountain Cancer Centers-Rose Denver Colorado
United States SCL Health Saint Joseph Hospital Denver Colorado
United States Broadlawns Medical Center Des Moines Iowa
United States Medical Oncology and Hematology Associates-Des Moines Des Moines Iowa
United States Mercy Medical Center - Des Moines Des Moines Iowa
United States Mission Cancer and Blood - Laurel Des Moines Iowa
United States Henry Ford Hospital Detroit Michigan
United States Wayne State University/Karmanos Cancer Institute Detroit Michigan
United States Illinois CancerCare-Dixon Dixon Illinois
United States Essentia Health Cancer Center Duluth Minnesota
United States Prisma Health Cancer Institute - Easley Easley South Carolina
United States Saint Luke's Hospital-Anderson Campus Easton Pennsylvania
United States University of Maryland Shore Medical Center at Easton Easton Maryland
United States Marshfield Medical Center-EC Cancer Center Eau Claire Wisconsin
United States STCC at DHR Health Institute for Research and Development Edinburg Texas
United States Swedish Cancer Institute-Edmonds Edmonds Washington
United States Carle Physician Group-Effingham Effingham Illinois
United States Crossroads Cancer Center Effingham Illinois
United States Arnot Ogden Medical Center/Falck Cancer Center Elmira New York
United States Mountain Blue Cancer Care Center - Swedish Englewood Colorado
United States Swedish Medical Center Englewood Colorado
United States Saint Vincent Hospital Erie Pennsylvania
United States Illinois CancerCare-Eureka Eureka Illinois
United States NorthShore University HealthSystem-Evanston Hospital Evanston Illinois
United States Sanford Broadway Medical Center Fargo North Dakota
United States Sanford Roger Maris Cancer Center Fargo North Dakota
United States Weisberg Cancer Treatment Center Farmington Hills Michigan
United States Augusta Health Center for Cancer and Blood Disorders Fishersville Virginia
United States McLaren Cancer Institute-Flint Flint Michigan
United States Singh and Arora Hematology Oncology PC Flint Michigan
United States Kaiser Permanente-Fontana Fontana California
United States Cancer Care and Hematology-Fort Collins Fort Collins Colorado
United States Poudre Valley Hospital Fort Collins Colorado
United States McFarland Clinic - Trinity Cancer Center Fort Dodge Iowa
United States Trinity Regional Medical Center Fort Dodge Iowa
United States Broward Health Medical Center Fort Lauderdale Florida
United States Regional Cancer Center-Lee Memorial Health System Fort Myers Florida
United States Beebe South Coastal Health Campus Frankford Delaware
United States Ascension Saint Francis - Reiman Cancer Center Franklin Wisconsin
United States Saint Luke's Cancer Institute - Fruitland Fruitland Idaho
United States University of Florida Health Science Center - Gainesville Gainesville Florida
United States Kaiser Permanente-Gaithersburg Medical Center Gaithersburg Maryland
United States Illinois CancerCare-Galesburg Galesburg Illinois
United States NorthShore University HealthSystem-Glenbrook Hospital Glenview Illinois
United States National Jewish Health-Western Hematology Oncology Golden Colorado
United States Southeastern Medical Oncology Center-Goldsboro Goldsboro North Carolina
United States Altru Cancer Center Grand Forks North Dakota
United States Spectrum Health at Butterworth Campus Grand Rapids Michigan
United States Benefis Healthcare- Sletten Cancer Institute Great Falls Montana
United States Great Falls Clinic Great Falls Montana
United States North Colorado Medical Center Greeley Colorado
United States UCHealth Greeley Hospital Greeley Colorado
United States Bellin Memorial Hospital Green Bay Wisconsin
United States Prisma Health Cancer Institute - Butternut Greenville South Carolina
United States Prisma Health Cancer Institute - Eastside Greenville South Carolina
United States Prisma Health Cancer Institute - Faris Greenville South Carolina
United States Saint Francis Cancer Center Greenville South Carolina
United States Saint Francis Hospital Greenville South Carolina
United States Prisma Health Cancer Institute - Greer Greer South Carolina
United States Baptist Cancer Center-Grenada Grenada Mississippi
United States The Cancer Institute of New Jersey Hamilton Hamilton New Jersey
United States Kaiser Permanente - Harbor City Harbor City California
United States UPMC Pinnacle Cancer Center/Community Osteopathic Campus Harrisburg Pennsylvania
United States Hartford Hospital Hartford Connecticut
United States HaysMed University of Kansas Health System Hays Kansas
United States Saint Peter's Community Hospital Helena Montana
United States OptumCare Cancer Care at Seven Hills Henderson Nevada
United States Margaret R Pardee Memorial Hospital Hendersonville North Carolina
United States Essentia Health Hibbing Clinic Hibbing Minnesota
United States NorthShore University HealthSystem-Highland Park Hospital Highland Park Illinois
United States Houston Methodist Hospital Houston Texas
United States Lyndon Baines Johnson General Hospital Houston Texas
United States M D Anderson Cancer Center Houston Texas
United States MD Anderson West Houston Houston Texas
United States Community Cancer Center East Indianapolis Indiana
United States Community Cancer Center North Indianapolis Indiana
United States Community Cancer Center South Indianapolis Indiana
United States Franciscan Health Indianapolis Indianapolis Indiana
United States Indiana University/Melvin and Bren Simon Cancer Center Indianapolis Indiana
United States University of Iowa/Holden Comprehensive Cancer Center Iowa City Iowa
United States Kaiser Permanente-Irvine Irvine California
United States Swedish Cancer Institute-Issaquah Issaquah Washington
United States Allegiance Health Jackson Michigan
United States Baptist MD Anderson Cancer Center Jacksonville Florida
United States Southeastern Medical Oncology Center-Jacksonville Jacksonville North Carolina
United States Mercyhealth Hospital and Cancer Center - Janesville Janesville Wisconsin
United States McFarland Clinic - Jefferson Jefferson Iowa
United States Jefferson Hospital Jefferson Hills Pennsylvania
United States Wellmont Medical Associates Oncology and Hematology-Johnson City Johnson City Tennessee
United States UW Cancer Center Johnson Creek Johnson Creek Wisconsin
United States NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro Jonesboro Arkansas
United States Freeman Health System Joplin Missouri
United States Mercy Hospital Joplin Joplin Missouri
United States West Michigan Cancer Center Kalamazoo Michigan
United States Kalispell Regional Medical Center Kalispell Montana
United States Truman Medical Centers Kansas City Missouri
United States Vidant Oncology-Kenansville Kenansville North Carolina
United States Ochsner Medical Center Kenner Kenner Louisiana
United States Greater Dayton Cancer Center Kettering Ohio
United States Illinois CancerCare-Kewanee Clinic Kewanee Illinois
United States Kingman Regional Medical Center Kingman Arizona
United States Ballad Health Cancer Care - Kingsport Kingsport Tennessee
United States Wellmont Holston Valley Hospital and Medical Center Kingsport Tennessee
United States Vidant Oncology-Kinston Kinston North Carolina
United States Community Howard Regional Health Kokomo Indiana
United States Gundersen Lutheran Medical Center La Crosse Wisconsin
United States Franciscan Saint Elizabeth Health - Lafayette East Lafayette Indiana
United States Northwell Health/Center for Advanced Medicine Lake Success New York
United States Fairfield Medical Center Lancaster Ohio
United States Karmanos Cancer Institute at McLaren Greater Lansing Lansing Michigan
United States Sparrow Hospital Lansing Michigan
United States McLaren Cancer Institute-Lapeer Region Lapeer Michigan
United States Kaiser Permanente - Largo Medical Center Largo Maryland
United States Memorial Medical Center - Las Cruces Las Cruces New Mexico
United States OptumCare Cancer Care at Charleston Las Vegas Nevada
United States OptumCare Cancer Care at Fort Apache Las Vegas Nevada
United States OptumCare Cancer Care at MountainView Las Vegas Nevada
United States Lawrence Memorial Hospital Lawrence Kansas
United States Cancer Centers of Southwest Oklahoma Research Lawton Oklahoma
United States MD Anderson League City League City Texas
United States Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center Lebanon New Hampshire
United States Baptist Health Lexington Lexington Kentucky
United States Saint Joseph Hospital East Lexington Kentucky
United States University of Kentucky/Markey Cancer Center Lexington Kentucky
United States Rocky Mountain Cancer Centers-Littleton Littleton Colorado
United States Hope Cancer Clinic Livonia Michigan
United States Trinity Health Saint Mary Mercy Livonia Hospital Livonia Michigan
United States Rocky Mountain Cancer Centers-Sky Ridge Lone Tree Colorado
United States Kaiser Permanente Los Angeles Medical Center Los Angeles California
United States Kaiser Permanente West Los Angeles Los Angeles California
United States Norton Audubon Hospital and Medical Campus Louisville Kentucky
United States Norton Brownsboro Hospital and Medical Campus Louisville Kentucky
United States Norton Hospital Pavilion and Medical Campus Louisville Kentucky
United States McKee Medical Center Loveland Colorado
United States Medical Center of the Rockies Loveland Colorado
United States Lowell General Hospital Lowell Massachusetts
United States Kaiser Permanente Lutherville - Timonium Medical Center Lutherville Maryland
United States Centra Lynchburg Hematology-Oncology Clinic Inc Lynchburg Virginia
United States Illinois CancerCare-Macomb Macomb Illinois
United States University of Wisconsin Carbone Cancer Center Madison Wisconsin
United States Norris Cotton Cancer Center-Manchester Manchester New Hampshire
United States Cleveland Clinic Cancer Center Mansfield Mansfield Ohio
United States OhioHealth Mansfield Hospital Mansfield Ohio
United States Minnesota Oncology Hematology PA-Maplewood Maplewood Minnesota
United States Saint John's Hospital - Healtheast Maplewood Minnesota
United States Marietta Memorial Hospital Marietta Ohio
United States OhioHealth Marion General Hospital Marion Ohio
United States McFarland Clinic - Marshalltown Marshalltown Iowa
United States Marshfield Medical Center-Marshfield Marshfield Wisconsin
United States Fremont - Rideout Cancer Center Marysville California
United States Carle Physician Group-Mattoon/Charleston Mattoon Illinois
United States Hillcrest Hospital Cancer Center Mayfield Heights Ohio
United States Loyola University Medical Center Maywood Illinois
United States Kaiser Permanente Tysons Corner Medical Center McLean Virginia
United States Aspirus Medford Hospital Medford Wisconsin
United States Baptist Memorial Hospital and Cancer Center-Memphis Memphis Tennessee
United States Midstate Medical Center Meriden Connecticut
United States Saint Luke's Cancer Institute - Meridian Meridian Idaho
United States Woodland Cancer Care Center Michigan City Indiana
United States Health Partners Inc Minneapolis Minnesota
United States Hennepin County Medical Center Minneapolis Minnesota
United States Marshfield Clinic-Minocqua Center Minocqua Wisconsin
United States Community Medical Hospital Missoula Montana
United States Memorial Medical Center Modesto California
United States Forbes Hospital Monroeville Pennsylvania
United States Franciscan Health Mooresville Mooresville Indiana
United States West Virginia University Healthcare Morgantown West Virginia
United States Morristown Medical Center Morristown New Jersey
United States McLaren Cancer Institute-Macomb Mount Clemens Michigan
United States McLaren Cancer Institute-Central Michigan Mount Pleasant Michigan
United States Good Samaritan Regional Health Center Mount Vernon Illinois
United States Knox Community Hospital Mount Vernon Ohio
United States ProHealth D N Greenwald Center Mukwonago Wisconsin
United States Saint Alphonsus Cancer Care Center-Nampa Nampa Idaho
United States Saint Luke's Cancer Institute - Nampa Nampa Idaho
United States Dartmouth Cancer Center - Nashua Nashua New Hampshire
United States Allegheny Valley Hospital Natrona Heights Pennsylvania
United States Baptist Memorial Hospital and Cancer Center-Union County New Albany Mississippi
United States The Hospital of Central Connecticut New Britain Connecticut
United States Rutgers Cancer Institute of New Jersey New Brunswick New Jersey
United States Ochsner Medical Center Jefferson New Orleans Louisiana
United States Cancer Center of Western Wisconsin New Richmond Wisconsin
United States Laura and Isaac Perlmutter Cancer Center at NYU Langone New York New York
United States Helen F Graham Cancer Center Newark Delaware
United States Licking Memorial Hospital Newark Ohio
United States Medical Oncology Hematology Consultants PA Newark Delaware
United States Providence Newberg Medical Center Newberg Oregon
United States CTCA at Southeastern Regional Medical Center Newnan Georgia
United States Southwest VA Regional Cancer Center Norton Virginia
United States William Backus Hospital Norwich Connecticut
United States Henry Ford Medical Center-Columbus Novi Michigan
United States Cancer Care Center of O'Fallon O'Fallon Illinois
United States ProHealth Oconomowoc Memorial Hospital Oconomowoc Wisconsin
United States University of Oklahoma Health Sciences Center Oklahoma City Oklahoma
United States Olathe Health Cancer Center Olathe Kansas
United States Nebraska Methodist Hospital Omaha Nebraska
United States Kaiser Permanente-Ontario Ontario California
United States Saint Alphonsus Medical Center-Ontario Ontario Oregon
United States Saint Joseph Hospital - Orange Orange California
United States UC Irvine Health/Chao Family Comprehensive Cancer Center Orange California
United States Providence Willamette Falls Medical Center Oregon City Oregon
United States AdventHealth Orlando Orlando Florida
United States Ascension Mercy Hospital Oshkosh Wisconsin
United States Illinois CancerCare-Ottawa Clinic Ottawa Illinois
United States Baptist Memorial Hospital and Cancer Center-Oxford Oxford Mississippi
United States Kaiser Permanente - Panorama City Panorama City California
United States The Valley Hospital-Luckow Pavilion Paramus New Jersey
United States Camden Clark Medical Center Parkersburg West Virginia
United States Illinois CancerCare-Pekin Pekin Illinois
United States Illinois CancerCare-Peoria Peoria Illinois
United States Illinois CancerCare-Peru Peru Illinois
United States McLaren Cancer Institute-Northern Michigan Petoskey Michigan
United States FirstHealth of the Carolinas-Moore Regional Hospital Pinehurst North Carolina
United States Allegheny General Hospital Pittsburgh Pennsylvania
United States University of Pittsburgh Cancer Institute (UPCI) Pittsburgh Pennsylvania
United States West Penn Hospital Pittsburgh Pennsylvania
United States Newland Medical Associates-Pontiac Pontiac Michigan
United States Saint Joseph Mercy Oakland Pontiac Michigan
United States Baptist Regional Cancer Network-Cancer Center of Southeast Texas Port Arthur Texas
United States McLaren-Port Huron Port Huron Michigan
United States Jefferson Healthcare Port Townsend Washington
United States Providence Portland Medical Center Portland Oregon
United States Providence Saint Vincent Medical Center Portland Oregon
United States Southern Ohio Medical Center Portsmouth Ohio
United States Kootenai Clinic Cancer Services - Post Falls Post Falls Idaho
United States Illinois CancerCare-Princeton Princeton Illinois
United States Saint Luke's Hospital-Quakertown Campus Quakertown Pennsylvania
United States Ascension All Saints Hospital Racine Wisconsin
United States Beebe Health Campus Rehoboth Beach Delaware
United States Renown Regional Medical Center Reno Nevada
United States Ascension Saint Mary's Hospital Rhinelander Wisconsin
United States Marshfield Medical Center-Rice Lake Rice Lake Wisconsin
United States Vidant Oncology-Richlands Richlands North Carolina
United States VCU Massey Cancer Center at Stony Point Richmond Virginia
United States Virginia Cancer Institute Richmond Virginia
United States Virginia Commonwealth University/Massey Cancer Center Richmond Virginia
United States Valley Hospital Ridgewood New Jersey
United States Presbyterian Rust Medical Center/Jorgensen Cancer Center Rio Rancho New Mexico
United States Kaiser Permanente-Riverside Riverside California
United States University of Rochester Rochester New York
United States Penobscot Bay Medical Center Rockport Maine
United States Sutter Medical Center Sacramento Sacramento California
United States University of California Davis Comprehensive Cancer Center Sacramento California
United States Ascension Saint Mary's Hospital Saginaw Michigan
United States Oncology Hematology Associates of Saginaw Valley PC Saginaw Michigan
United States Norris Cotton Cancer Center-North Saint Johnsbury Vermont
United States Mercy Hospital Saint Louis Saint Louis Missouri
United States Saint Louis Cancer and Breast Institute-South City Saint Louis Missouri
United States Regions Hospital Saint Paul Minnesota
United States United Hospital Saint Paul Minnesota
United States Salina Regional Health Center Salina Kansas
United States Salinas Valley Memorial Salinas California
United States Huntsman Cancer Institute/University of Utah Salt Lake City Utah
United States Kaiser Permanente-San Diego Mission San Diego California
United States Kaiser Permanente-San Diego Zion San Diego California
United States Kaiser Permanente-San Marcos San Marcos California
United States Kootenai Cancer Clinic Sandpoint Idaho
United States Essentia Health Sandstone Sandstone Minnesota
United States North Coast Cancer Care Sandusky Ohio
United States MaineHealth/SMHC Cancer Care and Blood Disorders-Sanford Sanford Maine
United States Swedish Medical Center-First Hill Seattle Washington
United States Prisma Health Cancer Institute - Seneca Seneca South Carolina
United States Avera Cancer Institute Sioux Falls South Dakota
United States Sanford Cancer Center Oncology Clinic Sioux Falls South Dakota
United States Sanford USD Medical Center - Sioux Falls Sioux Falls South Dakota
United States Robert Wood Johnson University Hospital Somerset Somerville New Jersey
United States VCU Community Memorial Health Center South Hill Virginia
United States Maine Medical Partners - South Portland South Portland Maine
United States Baptist Memorial Hospital and Cancer Center-Desoto Southhaven Mississippi
United States Spartanburg Medical Center Spartanburg South Carolina
United States MultiCare Deaconess Cancer and Blood Specialty Center - Downtown Spokane Washington
United States MultiCare Deaconess Cancer and Blood Specialty Center - North Spokane Washington
United States Southern Illinois University School of Medicine Springfield Illinois
United States Springfield Clinic Springfield Illinois
United States Marshfield Medical Center-River Region at Stevens Point Stevens Point Wisconsin
United States MD Anderson in Sugar Land Sugar Land Texas
United States Overlook Hospital Summit New Jersey
United States ProMedica Flower Hospital Sylvania Ohio
United States Ascension Saint Joseph Hospital Tawas City Michigan
United States Scott and White Memorial Hospital Temple Texas
United States Union Hospital Terre Haute Indiana
United States National Jewish Health-Northern Hematology Oncology Thornton Colorado
United States University of Kansas Health System Saint Francis Campus Topeka Kansas
United States Munson Medical Center Traverse City Michigan
United States Cancer Treatment Centers of America Tulsa Oklahoma
United States Oklahoma Cancer Specialists and Research Institute-Tulsa Tulsa Oklahoma
United States Saint Luke's Cancer Institute - Twin Falls Twin Falls Idaho
United States Carle Cancer Center Urbana Illinois
United States Essentia Health Virginia Clinic Virginia Minnesota
United States John Muir Medical Center-Walnut Creek Walnut Creek California
United States South Pointe Hospital Warrensville Heights Ohio
United States Illinois CancerCare - Washington Washington Illinois
United States Kaiser Permanente-Capitol Hill Medical Center Washington District of Columbia
United States ProHealth Waukesha Memorial Hospital Waukesha Wisconsin
United States UW Cancer Center at ProHealth Care Waukesha Wisconsin
United States Aspirus Regional Cancer Center Wausau Wisconsin
United States Ascension Medical Group Southeast Wisconsin - Mayfair Road Wauwatosa Wisconsin
United States Henry Ford West Bloomfield Hospital West Bloomfield Michigan
United States Saint Mary's Oncology/Hematology Associates of West Branch West Branch Michigan
United States University of Cincinnati Cancer Center-West Chester West Chester Ohio
United States Mercy Medical Center-West Lakes West Des Moines Iowa
United States Reading Hospital West Reading Pennsylvania
United States Saint Ann's Hospital Westerville Ohio
United States Marshfield Medical Center - Weston Weston Wisconsin
United States University of Kansas Hospital-Westwood Cancer Center Westwood Kansas
United States Wexford Health and Wellness Pavilion Wexford Pennsylvania
United States SCL Health Lutheran Medical Center Wheat Ridge Colorado
United States Dickstein Cancer Treatment Center White Plains New York
United States Presbyterian Intercommunity Hospital Whittier California
United States Cancer Center of Kansas - Wichita Wichita Kansas
United States Cancer Center of Kansas-Wichita Medical Arts Tower Wichita Kansas
United States Asplundh Cancer Pavilion Willow Grove Pennsylvania
United States Wake Forest University Health Sciences Winston-Salem North Carolina
United States Aspirus Cancer Care - Wisconsin Rapids Wisconsin Rapids Wisconsin
United States Kaiser Permanente-Woodland Hills Woodland Hills California
United States Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus Ypsilanti Michigan
United States Genesis Healthcare System Cancer Care Center Zanesville Ohio

Sponsors (2)

Lead Sponsor Collaborator
National Cancer Institute (NCI) NRG Oncology

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Other Severity of fatigue Will use the ITT population. Measured by the Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue questionnaire. Will be compared between the control arm (Chemo-bevacizumab [Bev]) and the experimental arm by means of ordinal logistic regression with adjustment for the corresponding baseline measurement and stratification variables. The comparison will be performed at the significance level of 0.05 (two-sided) and the clinical meaningfulness of the comparison will be considered. At 16 weeks
Other Physical functioning Will use the ITT population. Measured by the European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life questionnaire (QLQ)-C30 physical functioning scale. Will be compared between the control arm (Chemo-Bev) and the experimental arm by means of ordinal logistic regression with adjustment for the corresponding baseline measurement and stratification variables. The comparison will be performed at the significance level of 0.05 (two-sided) and the clinical meaningfulness of the comparison will be considered. At 16 weeks
Other Health utility scores Will use the ITT population. Will be measured using the EuroQoL 5 Dimensions 5 Levels (EQ-5D-5L) questionnaire. Up to 5 years
Other Proportion of patients reporting each response option at each assessment timepoint by treatment arm for item GP5 from the Functional Assessment of Cancer Therapy - General (FACT-G) Will use the ITT population. Up to 5 years
Other Intratumoral lymphocyte PD-L1+ expression (>= 1 % is positive) by immunohistochemistry (IHC) as a predictive biomarker of efficacy Will use the ITT population. Up to 5 years
Other Efficacy dependent on the number of somatic mutations Will use the ITT population. Up to 5 years
Other Efficacy in tumors with MLH1 silencing Will use the ITT population. Up to 5 years
Other Change in quantification of cell free deoxyribonucleic acid (cfDNA) mutations Will use the ITT population. Baseline up to 5 years
Other Development of progression or relapse to treatment in cfDNA Will use the ITT population. Up to 5 years
Other Changes in T-cell repertoire diversity as a predictive biomarker of efficacy Will use the ITT population. Baseline up to 5 years
Other PFS of patients with high levels of diversity Compared to patients with low levels of diversity. Will use the ITT population. Up to 5 years
Other Change in T-cell diversity Will use the ITT population. Baseline to first restaging between immunotherapy arms and the standard of care arm
Other Mechanism of immune resistance to PD-1 blockade in mismatch repair deficient (dMMR)/microsatellite instability-high metastatic colorectal cancer (mCRC) by comparative analysis of tumor samples collected Will use the ITT population. Baseline up to 5 years
Primary Progression free survival (PFS) The analysis set is intent-to-treat (ITT). The experimental arms will be compared to the control arm by the log-rank test stratified by BRAF status (V600E mutation or not), metastatic disease: (liver-only, extra-hepatic), and prior adjuvant therapy for colon cancer (yes, no). Hazard ratios and associated confidence intervals from a stratified Cox regression model will also be reported along with estimates of the distributions of time to PFS event by the method of Kaplan and Meier. Sensitivity analyses accounting for 2 or more consecutively missed scheduled tumor imaging scans before progression/death will also be conducted. From the time from randomization until first confirmed progression or death from any cause, assessed up to 5 years
Secondary Overall survival (OS) Will be analyzed using the stratified log rank test and the ITT population. Kaplan-Meier plots will illustrate the distribution of these endpoints by treatment. Stratified Cox regression models will be used to estimate hazard ratios and associated confidence intervals. The time from randomization to death from any cause, assessed up to 5 years
Secondary Objective response rate (ORR) (complete response [CR] or partial response [PR]) Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Will be analyzed by a logistic regression models that control for the stratification factors (BRAF status, liver involvement, and adjuvant chemotherapy [chemo]) using the ITT population. Observed proportions along with confidence intervals will be presented by treatment. Up to 5 years
Secondary Incidence of adverse events Defined by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The safety profile will be described by tabulating the maximum observed grade of adverse event for each individual adverse event, for each system organ class, and overall using the Safety population. Up to 30 days after last cycle
Secondary Rate of PFS At 12 months
Secondary Disease control rate (CR + PR + stable disease [SD]) Assessed by RECIST 1.1. Will be analyzed by a logistic regression models that control for the stratification factors (BRAF status, liver involvement, and adjuvant chemo) using the ITT population. Observed proportions along with confidence intervals will be presented by treatment. At 12 months
Secondary Duration of overall response (CR or PR) Assessed by RECIST 1.1. Will be analyzed using the stratified log rank test and the ITT population. Kaplan-Meier plots will illustrate the distribution of these endpoints by treatment. Stratified Cox regression models will be used to estimate hazard ratios and associated confidence intervals. From the time of first response to first confirmed progression by the study investigator or death from any cause, assessed up to 5 years
Secondary Duration of SD Assessed per RECIST 1.1. Will be analyzed using the stratified log rank test and the ITT population. Kaplan-Meier plots will illustrate the distribution of these endpoints by treatment. Stratified Cox regression models will be used to estimate hazard ratios and associated confidence intervals. From the time of first on-study assessment of SD to first progression by the study investigator or death from any cause, assessed up to 5 years
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