Advanced Extrapulmonary Neuroendocrine Carcinoma Clinical Trial
Official title:
Randomized Phase II/III Trial of First Line Platinum/Etoposide With or Without Atezolizumab (NSC#783608) in Patients With Advanced or Metastatic Poorly Differentiated Extrapulmonary Neuroendocrine Carcinomas (NEC)
| Verified date | March 2024 |
| Source | National Cancer Institute (NCI) |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
This phase II/III trial compares the effect of immunotherapy with atezolizumab in combination with standard chemotherapy with a platinum drug (cisplatin or carboplatin) and etoposide versus standard therapy alone for the treatment of poorly differentiated extrapulmonary (originated outside the lung) neuroendocrine cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started (primary site) to other places in the body (metastatic). The other aim of this trial is to compare using atezolizumab just at the beginning of treatment versus continuing it beyond the initial treatment. 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. Cisplatin and carboplatin are in a class of medications known as platinum-containing compounds that work by killing, stopping or slowing the growth of cancer cells. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair, and it may kill cancer cells. Giving atezolizumab in combination with a platinum drug (cisplatin or carboplatin) and etoposide may work better in treating patients with poorly differentiated extrapulmonary neuroendocrine cancer compared to standard therapy with a platinum drug (cisplatin or carboplatin) and etoposide alone.
| Status | Recruiting |
| Enrollment | 189 |
| Est. completion date | October 1, 2028 |
| Est. primary completion date | October 1, 2028 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | Inclusion Criteria: - Participants must have histologically-confirmed (local site pathological confirmation sufficient) extrapulmonary poorly differentiated, neuroendocrine carcinoma (NEC) - Participants must have disease that is unresectable or metastatic and not eligible for definitive therapy as deemed per the treating investigator - Participants must have radiologically evaluable disease, measurable or non-measurable, per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. All measurable and non-measurable lesions must be assessed by CT scan with IV contrast of the chest/abdomen/and pelvis (or CT chest without contrast and MRI abdomen/pelvis with gadolinium contrast, if contraindication to CT iodinated contrast) within 28 days prior to registration. While may be used for routine clinical evaluation, PET scans and bone scans alone are not acceptable for disease assessment while participating in this study. All known sites of disease must be assessed and documented on the Baseline Tumor Assessment Form - Participants must have brain MRI (or CT head with contrast if there is contraindication to MRI brain) if clinically indicated within 28 days prior to registration. Note: Brain imaging is not required in participants without known and/or clinical concern for brain metastases. Participants with asymptomatic central nervous system (CNS) metastases are eligible if one or more of the following apply: - Participants who have received treatment for brain metastases must have: - No evidence of radiological progression (by MRI brain or CT head with contrast if there is contraindication to MRI brain) within 28 days prior to registration - Discontinued all corticosteroids at least 14 days prior to registration - Participants with treatment-naive brain lesions must have: - No lesion measuring > 2.0 cm in size in any axis - MRI brain or CT head with contrast (if there is contraindication to MRI brain) demonstrating no evidence for mass effect, edema, or other impending neurological compromise within 28 days prior to registration - No evidence of radiological progression (by MRI brain or CT head with contrast if there is contraindication to MRI brain) within 28 days prior to registration - No need for > 2 mg of dexamethasone (or equivalent of > 10 mg prednisone) per day at time of registration - Participants must not have symptomatic central nervous system (CNS) metastases - Participants must not have known or suspected leptomeningeal disease - Participants with prior history of non-metastatic (localized/locally advanced disease) extrapulmonary poorly differentiated NEC may have had prior platinum-based therapy +/- radiation +/- surgery provided that all therapy was completed >= 6 months prior to registration - Participants must discontinue denosumab prior to study registration and plan to replace with a bisphosphonate while on the study - Participants must not have had prior treatment for advanced or metastatic NEC EXCEPT one cycle of platinum (carboplatin/cisplatin) + etoposide is allowed prior to registration. Other chemotherapy regimens are not allowed. For participants with prostate or urothelial NEC, prior chemotherapy for the non-NEC component (e.g. adenocarcinoma or urothelial) is allowed as long as such therapy was completed >= 24 weeks prior to registration and participants have recovered from all prior toxicities to =< grade 1. - Participants must not have had prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, CD137 agonists, anti-CTLA-4 agent, or any other immune checkpoint inhibitors for any neuroendocrine neoplasm. Immune checkpoint inhibitors given for other cancer indications are allowed provided last therapy was given at least 12 months prior to study registration - Participants must not have received treatment with systemic immunostimulatory agents including, but not limited to, interferon and interleukin2 [IL-2] within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to registration - Participants must not have had history of known severe allergy, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies, including to Chinese hamster ovary cell products or to any component of the atezolizumab formulation, cisplatin, carboplatin, or etoposide - Participants must not be on active systemic therapy for another cancer with the exception of hormonal therapy including androgen deprivation therapy (e.g., gonadotropin-releasing hormone [GnRH] agonists or antagonists), which can be continued while participants are receiving protocol therapy. Use of enzalutamide or apalutamide is permitted after completion of chemotherapy and must be held during chemotherapy for participants receiving prior to enrollment. Use of darolutamide is permitted during chemotherapy. Glucocorticoid-containing regimens, including abiraterone, are not permitted. - Participants must be >= 18 years of age - Participants must have a Zubrod performance status of =< 2 within 28 days prior to registration - Participants must have a complete medical history and physical exam within 28 days prior to registration - Absolute neutrophil count (ANC) >= 1.5 x 10^9 /L (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests) - Hemoglobin >= 9.0 g/dl (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests) - Platelet count >= 100 x 10^9/L (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests) - Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x institutional upper limit of normal (ULN) (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests) - Serum total bilirubin =< 1.5 x ULN (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests) - Adequate renal function as defined by any 1 of the following: 1) Measured creatinine clearance (CL) > 50 mL/min OR 2) Calculated creatinine CL > 50 mL/min by the Cockcroft-Gault formula OR by 24-hour urine collection for determination of creatinine clearance (obtained within 14 days prior to registration. For participants who received a cycle of chemotherapy prior to registration, at least 21 days must have elapsed between day 1 of platinum + etoposide and performance of these tests) - Participants must not have uncontrolled or symptomatic hypercalcemia (> 1.5 mmol/L ionized calcium or calcium > 12 mg/dL or corrected serum calcium > ULN) within 14 days prior to registration. Participants who have asymptomatic hypercalcemia are eligible provided that medical therapy to treat the hypercalcemia is planned - Participants must not have a diagnosis of immunodeficiency nor be receiving systemic steroid therapy (equivalent of > 20 mg of hydrocortisone per day) or any other form of immunosuppressive therapy within 14 days prior to registration - Participants must not have active or history of autoimmune disease or immune deficiency, including, but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome, or multiple sclerosis with the following exceptions: - Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study - Patients with controlled type 1 diabetes mellitus who are on an insulin regimen are eligible for the study - Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met: - Rash must cover < 10% of body surface area - Disease is well controlled at baseline and requires only low-potency topical corticosteroids - No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months - Participants must not have history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. NOTE: History of radiation pneumonitis in the radiation field (fibrosis) is permitted - Participants must not have significant cardiovascular disease, such as New York Heart Association class II or greater cardiac disease, myocardial infarction within 3 months prior to registration, unstable arrythmias, or unstable angina - Participants must not have had a major surgical procedure other than for diagnosis within 28 days prior to registration. Participant must not plan to receive a major surgical procedure during the course of protocol treatment. NOTE: Patient port placement is not considered a major surgery - Participants must not have severe infections (i.e., Common Terminology Criteria for Adverse Events [CTCAE] grade >= 2) at time of registration, including but not limited to hospitalization for complications for infection, bacteremia, or severe pneumonia - Participants must not have known active tuberculosis - Participants with evidence of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load, with testing performed as clinically indicated - Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants with active HCV infection who are currently on treatment must have an undetectable HCV viral load, with testing performed as clinically indicated - Participants with known human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at time of registration and have undetectable HIV viral load within 6 months of registration - Participants must not have prior allogeneic bone marrow transplantation or solid organ transplant - Participants must not have received administration of a live, attenuated vaccine (e.g., FluMist [registered trademark]) within 28 days prior to initiation of study treatment, during treatment with atezolizumab, and not plan to receive for 5 months after the last dose of atezolizumab - Participants must not be pregnant due to the possibility of harm to the fetus. Individuals who are of reproductive potential must have agreed to use an effective contraceptive method (with details provided as a part of the consent process) during the treatment period and for 5 months after the final dose of atezolizumab. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of "reproductive potential." In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in the semen - Participants must be offered the opportunity to participate in specimen banking. With participant consent, specimens must be collected and submitted via the Southwest Oncology Group (SWOG) Specimen Tracking System - Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines |
| Country | Name | City | State |
|---|---|---|---|
| United States | Hawaii Cancer Care - Westridge | 'Aiea | Hawaii |
| United States | Pali Momi Medical Center | 'Aiea | Hawaii |
| United States | Mary Greeley Medical Center | Ames | Iowa |
| United States | McFarland Clinic - Ames | Ames | Iowa |
| United States | Kaiser Permanente-Anaheim | Anaheim | California |
| United States | Mission Cancer and Blood - Ankeny | Ankeny | Iowa |
| United States | Saint Joseph Mercy Hospital | Ann Arbor | Michigan |
| United States | University of Michigan Comprehensive Cancer Center | Ann Arbor | Michigan |
| United States | Sutter Auburn Faith Hospital | Auburn | California |
| United States | Sutter Cancer Centers Radiation Oncology Services-Auburn | Auburn | California |
| United States | Kaiser Permanente-Baldwin Park | Baldwin Park | California |
| United States | LSU Health Baton Rouge-North Clinic | Baton Rouge | Louisiana |
| United States | Our Lady of the Lake Physicians Group - Medical Oncology | Baton Rouge | Louisiana |
| United States | Kaiser Permanente-Bellflower | Bellflower | California |
| United States | Alta Bates Summit Medical Center-Herrick Campus | Berkeley | California |
| United States | McFarland Clinic - Boone | Boone | Iowa |
| United States | Saint Joseph Mercy Brighton | Brighton | Michigan |
| United States | Trinity Health IHA Medical Group Hematology Oncology - Brighton | Brighton | Michigan |
| United States | Henry Ford Cancer Institute-Downriver | Brownstown | Michigan |
| United States | Roswell Park Cancer Institute | Buffalo | New York |
| United States | Sutter Cancer Centers Radiation Oncology Services-Cameron Park | Cameron Park | California |
| 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 | Mercy Cancer Center - Carmichael | Carmichael | California |
| United States | Mercy San Juan Medical Center | Carmichael | California |
| United States | Centralia Oncology Clinic | Centralia | Illinois |
| United States | Medical University of South Carolina | Charleston | South Carolina |
| United States | Atrium Health University City/LCI-University | Charlotte | North Carolina |
| United States | Carolinas Medical Center/Levine Cancer Institute | Charlotte | North Carolina |
| United States | Levine Cancer Institute-Ballantyne | Charlotte | North Carolina |
| United States | Levine Cancer Institute-SouthPark | Charlotte | North Carolina |
| United States | Saint Joseph Mercy Chelsea | Chelsea | Michigan |
| United States | Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital | Chelsea | Michigan |
| United States | Northwestern University | Chicago | Illinois |
| United States | University of Chicago Comprehensive Cancer Center | Chicago | Illinois |
| United States | Providence Cancer Institute Clackamas Clinic | Clackamas | Oregon |
| 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 | Ohio State University Comprehensive Cancer Center | Columbus | Ohio |
| United States | Atrium Health Cabarrus/LCI-Concord | Concord | North Carolina |
| United States | Greater Regional Medical Center | Creston | Iowa |
| United States | UT Southwestern Simmons Cancer Center - RedBird | Dallas | Texas |
| United States | UT Southwestern/Simmons Cancer Center-Dallas | Dallas | Texas |
| United States | Carle at The Riverfront | Danville | Illinois |
| United States | Beaumont Hospital - Dearborn | Dearborn | Michigan |
| United States | Cancer Care Specialists of Illinois - Decatur | Decatur | Illinois |
| United States | Decatur Memorial Hospital | Decatur | Illinois |
| United States | Northwestern Medicine Cancer Center Kishwaukee | DeKalb | Illinois |
| United States | Smilow Cancer Hospital-Derby Care Center | Derby | Connecticut |
| 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 | Ascension Saint John Hospital | Detroit | Michigan |
| United States | Henry Ford Hospital | Detroit | Michigan |
| United States | Wayne State University/Karmanos Cancer Institute | Detroit | Michigan |
| United States | Saint Luke's Hospital of Duluth | Duluth | Minnesota |
| United States | Marshfield Medical Center-EC Cancer Center | Eau Claire | Wisconsin |
| United States | Fairview Southdale Hospital | Edina | Minnesota |
| United States | Carle Physician Group-Effingham | Effingham | Illinois |
| United States | Crossroads Cancer Center | Effingham | Illinois |
| United States | Mercy Cancer Center - Elk Grove | Elk Grove | California |
| United States | Smilow Cancer Hospital Care Center-Fairfield | Fairfield | Connecticut |
| United States | Beaumont Hospital - Farmington Hills | Farmington Hills | Michigan |
| United States | Weisberg Cancer Treatment Center | Farmington Hills | Michigan |
| United States | Genesee Cancer and Blood Disease Treatment Center | Flint | Michigan |
| United States | Genesee Hematology Oncology PC | Flint | Michigan |
| United States | Genesys Hurley Cancer Institute | Flint | Michigan |
| United States | Hurley Medical Center | Flint | Michigan |
| United States | Kaiser Permanente-Fontana | Fontana | California |
| United States | McFarland Clinic - Trinity Cancer Center | Fort Dodge | Iowa |
| United States | Holy Cross Hospital | Fort Lauderdale | Florida |
| United States | UT Southwestern/Simmons Cancer Center-Fort Worth | Fort Worth | Texas |
| United States | Palo Alto Medical Foundation-Fremont | Fremont | California |
| United States | Levine Cancer Institute-Gaston | Gastonia | North Carolina |
| United States | Northwestern Medicine Cancer Center Delnor | Geneva | Illinois |
| United States | Smilow Cancer Hospital Care Center at Glastonbury | Glastonbury | Connecticut |
| United States | Northwestern Medicine Glenview Outpatient Center | Glenview | Illinois |
| United States | Southeastern Medical Oncology Center-Goldsboro | Goldsboro | North Carolina |
| United States | Northwestern Medicine Grayslake Outpatient Center | Grayslake | Illinois |
| United States | Smilow Cancer Hospital Care Center at Greenwich | Greenwich | Connecticut |
| United States | Smilow Cancer Hospital Care Center - Guilford | Guilford | Connecticut |
| United States | Kaiser Permanente - Harbor City | Harbor City | California |
| United States | Smilow Cancer Hospital Care Center at Saint Francis | Hartford | Connecticut |
| United States | Ingalls Memorial Hospital | Harvey | Illinois |
| United States | Hawaii Cancer Care Inc - Waterfront Plaza | Honolulu | Hawaii |
| United States | Queen's Cancer Cenrer - POB I | Honolulu | Hawaii |
| United States | Queen's Cancer Center - Kuakini | Honolulu | Hawaii |
| United States | Queen's Medical Center | Honolulu | Hawaii |
| United States | Straub Clinic and Hospital | Honolulu | Hawaii |
| United States | Kaiser Permanente-Irvine | Irvine | California |
| United States | Southeastern Medical Oncology Center-Jacksonville | Jacksonville | North Carolina |
| United States | McFarland Clinic - Jefferson | Jefferson | Iowa |
| United States | Mercy Hospital Joplin | Joplin | Missouri |
| United States | Gundersen Lutheran Medical Center | La Crosse | Wisconsin |
| United States | Northwestern Medicine Lake Forest Hospital | Lake Forest | Illinois |
| United States | Cancer Centers of Southwest Oklahoma Research | Lawton | Oklahoma |
| United States | Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center | Lebanon | New Hampshire |
| United States | Trinity Health Saint Mary Mercy Livonia Hospital | Livonia | Michigan |
| United States | Kaiser Permanente Los Angeles Medical Center | Los Angeles | California |
| United States | Kaiser Permanente West Los Angeles | Los Angeles | California |
| United States | McFarland Clinic - Marshalltown | Marshalltown | Iowa |
| United States | Marshfield Medical Center-Marshfield | Marshfield | Wisconsin |
| United States | Carle Physician Group-Mattoon/Charleston | Mattoon | Illinois |
| United States | Abbott-Northwestern Hospital | Minneapolis | Minnesota |
| United States | Marshfield Clinic-Minocqua Center | Minocqua | Wisconsin |
| United States | Memorial Medical Center | Modesto | California |
| United States | West Virginia University Healthcare | Morgantown | West Virginia |
| United States | Palo Alto Medical Foundation-Camino Division | Mountain View | California |
| United States | Vanderbilt University/Ingram Cancer Center | Nashville | Tennessee |
| United States | Yale University | New Haven | Connecticut |
| United States | UC Comprehensive Cancer Center at Silver Cross | New Lenox | Illinois |
| United States | University Medical Center New Orleans | New Orleans | Louisiana |
| United States | Mount Sinai Hospital | New York | New York |
| United States | Providence Newberg Medical Center | Newberg | Oregon |
| United States | Yale-New Haven Hospital North Haven Medical Center | North Haven | Connecticut |
| United States | Cancer Care Center of O'Fallon | O'Fallon | Illinois |
| United States | University of Oklahoma Health Sciences Center | Oklahoma City | Oklahoma |
| United States | Kaiser Permanente-Ontario | Ontario | California |
| United States | Providence Willamette Falls Medical Center | Oregon City | Oregon |
| United States | Northwestern Medicine Orland Park | Orland Park | Illinois |
| United States | University of Chicago Medicine-Orland Park | Orland Park | Illinois |
| United States | Palo Alto Medical Foundation Health Care | Palo Alto | California |
| United States | Kaiser Permanente - Panorama City | Panorama City | California |
| United States | Parker Adventist Hospital | Parker | Colorado |
| United States | Cancer Center at Saint Joseph's | Phoenix | Arizona |
| United States | FirstHealth of the Carolinas-Moore Regional Hospital | Pinehurst | North Carolina |
| United States | Providence Portland Medical Center | Portland | Oregon |
| United States | Providence Saint Vincent Medical Center | Portland | Oregon |
| United States | Marshfield Medical Center-Rice Lake | Rice Lake | Wisconsin |
| United States | UT Southwestern Clinical Center at Richardson/Plano | Richardson | Texas |
| United States | Kaiser Permanente-Riverside | Riverside | California |
| United States | Mayo Clinic in Rochester | Rochester | Minnesota |
| United States | Mercy Cancer Center - Rocklin | Rocklin | California |
| United States | Sutter Cancer Centers Radiation Oncology Services-Roseville | Roseville | California |
| United States | Sutter Roseville Medical Center | Roseville | California |
| United States | William Beaumont Hospital-Royal Oak | Royal Oak | Michigan |
| United States | Mercy Cancer Center - Sacramento | Sacramento | California |
| United States | Sutter Medical Center Sacramento | Sacramento | California |
| United States | Norris Cotton Cancer Center-North | Saint Johnsbury | Vermont |
| United States | Park Nicollet Clinic - Saint Louis Park | Saint Louis Park | Minnesota |
| United States | Regions Hospital | Saint Paul | Minnesota |
| United States | Huntsman Cancer Institute/University of Utah | Salt Lake City | Utah |
| United States | Kaiser Permanente-San Diego Zion | San Diego | California |
| United States | California Pacific Medical Center-Pacific Campus | San Francisco | California |
| United States | Kaiser Permanente-San Marcos | San Marcos | California |
| United States | Palo Alto Medical Foundation-Santa Cruz | Santa Cruz | California |
| United States | FHCC South Lake Union | Seattle | Washington |
| United States | Fred Hutchinson Cancer Research Center | Seattle | Washington |
| United States | University of Washington Medical Center - Montlake | Seattle | Washington |
| United States | CoxHealth South Hospital | Springfield | Missouri |
| United States | Memorial Medical Center | Springfield | Illinois |
| United States | Southern Illinois University School of Medicine | Springfield | Illinois |
| United States | Springfield Clinic | Springfield | Illinois |
| United States | Smilow Cancer Hospital Care Center at Long Ridge | Stamford | Connecticut |
| United States | Marshfield Medical Center-River Region at Stevens Point | Stevens Point | Wisconsin |
| United States | Stony Brook University Medical Center | Stony Brook | New York |
| United States | Palo Alto Medical Foundation-Sunnyvale | Sunnyvale | California |
| United States | Moffitt Cancer Center | Tampa | Florida |
| United States | Toledo Clinic Cancer Centers-Toledo | Toledo | Ohio |
| United States | Smilow Cancer Hospital-Torrington Care Center | Torrington | Connecticut |
| United States | William Beaumont Hospital - Troy | Troy | Michigan |
| United States | Smilow Cancer Hospital Care Center-Trumbull | Trumbull | Connecticut |
| United States | Carle Cancer Center | Urbana | Illinois |
| United States | Sutter Solano Medical Center/Cancer Center | Vallejo | California |
| United States | Saint John Macomb-Oakland Hospital | Warren | Michigan |
| United States | Northwestern Medicine Cancer Center Warrenville | Warrenville | Illinois |
| United States | Smilow Cancer Hospital-Waterbury Care Center | Waterbury | Connecticut |
| United States | Smilow Cancer Hospital Care Center - Waterford | Waterford | Connecticut |
| United States | Mercy Medical Center-West Lakes | West Des Moines | Iowa |
| United States | Smilow Cancer Hospital Care Center - Westerly | Westerly | Rhode Island |
| United States | Marshfield Medical Center - Weston | Weston | Wisconsin |
| United States | Woodland Memorial Hospital | Woodland | California |
| United States | Kaiser Permanente-Woodland Hills | Woodland Hills | California |
| United States | Huron Gastroenterology PC | Ypsilanti | Michigan |
| United States | Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus | Ypsilanti | Michigan |
| Lead Sponsor | Collaborator |
|---|---|
| National Cancer Institute (NCI) |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Overall survival | Log-rank tests stratified by the randomization stratification factors will be used for null hypothesis (efficacy) tests. Cox regression models stratified by the randomization stratification factors will be used for alternative hypothesis (futility) tests. | From date of registration or from date of start of observation/maintenance therapy to date of death due to any cause, assessed up to 5 years | |
| Secondary | Progression-free survival | Will be estimated using the Kaplan-Meier method and compared using log-rank tests. | From date of registration or start of observation/maintenance therapy to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 5 years | |
| Secondary | Duration of response | Will be estimated non-parametrically using cumulative incidence curves. | Time from date of initial response to date of progression or death, assessed up to 5 years | |
| Secondary | Objective response rate (confirmed complete response [CR] or partial response [PR]) | Will be tabulated and compared between arms using Fisher's exact test. | Up to 5 years from study enrollment | |
| Secondary | Clinical benefit rate (confirmed CR or PR of any amount of time or stable disease for 6 months or longer) | Will be tabulated and compared between arms using Fisher's exact test. | Up to 5 years from study enrollment |