Testing Nivolumab and Ipilimumab With Short-Course Radiation in Locally Advanced Rectal Cancer

Stage III Rectal Cancer AJCC v8 Clinical Trial

Official title:

A Phase II Study of Neoadjuvant Nivolumab Plus Ipilimumab and Short-Course Radiation in MSI-H/dMMR Locally Advanced Rectal Adenocarcinoma

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT04751370
• Other study ID #: NCI-2021-00912
• Secondary ID: NCI-2021-00912EA
• Status: Suspended
• Phase: Phase 2
• Start date: February 8, 2022
• Est. completion date: December 31, 2026

Study information

• Verified date: April 2024
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II trial investigates the effect of nivolumab and ipilimumab when given together with short-course radiation therapy in treating patients with rectal cancer that has spread to nearby tissue or lymph nodes (locally advanced). Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving nivolumab, ipilimumab, and radiation therapy may kill more cancer cells.

Description:

PRIMARY OBJECTIVE: I. To demonstrate that neoadjuvant nivolumab and ipilimumab in combination with short-course radiation will improve the pathologic complete response rate (pCR) in microsatellite instability-high (MSI-H)/mismatch repair deficiency (dMMR) locally advanced rectal adenocarcinoma at total mesorectal excision (TME). SECONDARY OBJECTIVES: I. To demonstrate that neoadjuvant nivolumab and ipilimumab in combination with short-course radiation will improve the rate of sphincter preservation in low-lying tumors. II. To demonstrate that neoadjuvant nivolumab and ipilimumab in combination with short-course radiation will improve 5-year disease-free survival (DFS). III. To demonstrate that neoadjuvant nivolumab and ipilimumab in combination with short-course radiation will improve overall survival (OS). IV. To demonstrate that neoadjuvant nivolumab and ipilimumab in combination with short-course radiation will have acceptable safety/toxicity. OUTLINE: Patients receive nivolumab intravenously (IV) over 30 minutes and ipilimumab IV over 90 minutes on day 1. Treatment repeats every 28 days for 2 cycles. Starting at least 2 weeks but no longer than 6 weeks after completion of cycle 2 of nivolumab and ipilimumab, patients undergo short-course radiation therapy of 5 fractions daily for 1 week. Patients then continue to receive nivolumab IV over 30 minutes and ipilimumab IV over 90 minutes on day 1. Treatment repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity. 8-12 weeks after completion of 4th cycle of nivolumab and ipilimumab, patients undergo TME. Patients also undergo magnetic resonance imaging (MRI) and computed tomography (CT) prior to TME and during follow up, and undergo sigmoidoscopy prior to TME. After completion of study treatment, patients are followed up for 5 years.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 31
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient must be >= 18 years of age
• Patient must have histologically confirmed adenocarcinoma of the rectum with the inferior margin within 15 cm from the anal verge based on colonoscopy and/or flexible sigmoidoscopy
• Patient must have T3-4Nx or TxN+ disease (stage II or III) based on magnetic resonance imaging of the pelvis and computed tomography of the chest and abdomen. These baseline scans must be done within 28 days prior to registration
• Patient must have MSI-H (microsatellite instability-high) or dMMR (deficient mismatch repair) tumors based on immunohistochemistry or PCR (polymerase chain reaction)
• Patient must have Eastern Cooperative Oncology Group (ECOG) Performance status 0-2
• Patient must not have previously received chemotherapy or immunotherapy for rectal cancer
• Patient must not have previously received radiotherapy to the pelvis
• Patient must have the ability to understand and the willingness to sign a written informed consent document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible
• Patient must not have had major surgery performed within 28 days prior to registration
• Patient must not have a history of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline chest CT scan
• Patient must not have a serious active infection requiring IV antibiotics at time of registration
• Patient must agree to not receive live vaccines while on this study
• Patient must not have active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including chronic prolonged systemic corticosteroids (defined as corticosteroid use of duration one month or greater). These include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or anti-phospholipid syndrome. Patients with any of these are ineligible for this study because of the risk of recurrence or exacerbation of disease
• Patient must not have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to registration. Inhaled or topical steroids and adrenal replacement doses < 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if < 10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted
• Patient must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy. A repeat pregnancy test must be done within 72 hours prior to first dose of treatment if the baseline test was done outside the 72 hour window. A patient of childbearing potential is defined as anyone, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
• Patients of childbearing potential and sexually active patients must not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for at least one month (female patients) or one week (male patients) prior to the start of study drug and continue for 5 months after the last dose of study drug (for female patients). Investigators must counsel patients on the importance of pregnancy prevention and the implications of an unexpected pregnancy
• Leukocytes >= 3,000/mcL (must be obtained =< 14 days prior to protocol registration)
• Absolute neutrophil count (ANC) >= 1,500/mcL (must be obtained =< 14 days prior to protocol registration)
• Platelets >= 100,000/mcL (must be obtained =< 14 days prior to protocol registration)
• Total bilirubin =< institutional upper limit of normal (ULN) (must be obtained =< 14 days prior to protocol registration)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 x institutional ULN (must be obtained =< 14 days prior to protocol registration)
• Creatinine =< 1.5 x institutional ULN (must be obtained =< 14 days prior to protocol registration)
• Patients should have urine dipstick with proteinuria < 1. If urine dipstick > 2, proteinuria must be less than 1 g in 24 hours urine collection
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
• Patient must not have had live vaccines within 30 days prior to registration. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid (oral) vaccine. Patients are permitted to receive inactivated vaccines and any non-live vaccines including those for the seasonal influenza and COVID-19 (Note: intranasal influenza vaccines, such as Flu-Mist [registered trademark] are live attenuated vaccines and are not allowed). If possible, it is recommended to separate study drug administration from vaccine administration by about a week (primarily, in order to minimize an overlap of adverse events)

Related Conditions & MeSH terms

• Adenocarcinoma
• Locally Advanced Rectal Adenocarcinoma
• Rectal Neoplasms
• Stage II Rectal Cancer AJCC v8
• Stage III Rectal Cancer AJCC v8

Intervention

Procedure:
• Computed Tomography
Undergo CT

Biological:
• Ipilimumab
Given IV

Procedure:
• Magnetic Resonance Imaging
Undergo MRI

Biological:
• Nivolumab
Given IV

Radiation:
• Radiation Therapy
Undergo short-course radiation therapy

Procedure:
• Sigmoidoscopy
Undergo sigmoidoscopy
• Total Mesorectal Excision
Undergo TME

Locations

Country	Name	City	State
United States	Providence Regional Cancer System-Aberdeen	Aberdeen	Washington
United States	AdventHealth Altamonte	Altamonte Springs	Florida
United States	Mary Greeley Medical Center	Ames	Iowa
United States	McFarland Clinic - Ames	Ames	Iowa
United States	Alaska Breast Care and Surgery LLC	Anchorage	Alaska
United States	Alaska Oncology and Hematology LLC	Anchorage	Alaska
United States	Alaska Women's Cancer Care	Anchorage	Alaska
United States	Anchorage Associates in Radiation Medicine	Anchorage	Alaska
United States	Anchorage Oncology Centre	Anchorage	Alaska
United States	Katmai Oncology Group	Anchorage	Alaska
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	ThedaCare Regional Cancer Center	Appleton	Wisconsin
United States	PCR Oncology	Arroyo Grande	California
United States	Saint Louis Cancer and Breast Institute-Ballwin	Ballwin	Missouri
United States	Overlake Medical Center	Bellevue	Washington
United States	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington
United States	Saint Charles Health System	Bend	Oregon
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho
United States	Saint Luke's Cancer Institute - Boise	Boise	Idaho
United States	Central Care Cancer Center - Bolivar	Bolivar	Missouri
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Harrison Medical Center	Bremerton	Washington
United States	Saint Joseph Regional Cancer Center	Bryan	Texas
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Highline Medical Center-Main Campus	Burien	Washington
United States	Fairview Ridges Hospital	Burnsville	Minnesota
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 Francis Medical Center	Cape Girardeau	Missouri
United States	Southeast Cancer Center	Cape Girardeau	Missouri
United States	Memorial Hospital of Carbondale	Carbondale	Illinois
United States	Saint Anthony Regional Hospital	Carroll	Iowa
United States	SIH Cancer Institute	Carterville	Illinois
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Centralia Oncology Clinic	Centralia	Illinois
United States	Providence Regional Cancer System-Centralia	Centralia	Washington
United States	Christiana Care Health System-Concord Health Center	Chadds Ford	Pennsylvania
United States	University of Illinois	Chicago	Illinois
United States	Bethesda North Hospital	Cincinnati	Ohio
United States	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Providence Cancer Institute Clackamas Clinic	Clackamas	Oregon
United States	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Kootenai Health - Coeur d'Alene	Coeur d'Alene	Idaho
United States	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado
United States	Rocky Mountain Cancer Centers-Penrose	Colorado Springs	Colorado
United States	New Hampshire Oncology Hematology PA-Concord	Concord	New Hampshire
United States	Mercy Hospital	Coon Rapids	Minnesota
United States	Bay Area Hospital	Coos Bay	Oregon
United States	Greater Regional Medical Center	Creston	Iowa
United States	Carle at The Riverfront	Danville	Illinois
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Porter Adventist Hospital	Denver	Colorado
United States	Broadlawns Medical Center	Des Moines	Iowa
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist 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	Illinois CancerCare-Dixon	Dixon	Illinois
United States	Fairview Southdale Hospital	Edina	Minnesota
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	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Providence Regional Cancer Partnership	Everett	Washington
United States	Parkland Health Center - Farmington	Farmington	Missouri
United States	Mercy Hospital Fort Smith	Fort Smith	Arkansas
United States	Beebe South Coastal Health Campus	Frankford	Delaware
United States	Unity Hospital	Fridley	Minnesota
United States	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Western Illinois Cancer Treatment Center	Galesburg	Illinois
United States	Central Care Cancer Center - Garden City	Garden City	Kansas
United States	CHI Health Saint Francis	Grand Island	Nebraska
United States	Central Care Cancer Center - Great Bend	Great Bend	Kansas
United States	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	Comprehensive Cancer Centers of Nevada - Henderson	Henderson	Nevada
United States	OptumCare Cancer Care at Seven Hills	Henderson	Nevada
United States	CHI Saint Vincent Cancer Center Hot Springs	Hot Springs	Arkansas
United States	Swedish Cancer Institute-Issaquah	Issaquah	Washington
United States	Capital Region Southwest Campus	Jefferson City	Missouri
United States	Freeman Health System	Joplin	Missouri
United States	Mercy Hospital Joplin	Joplin	Missouri
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Providence Regional Cancer System-Lacey	Lacey	Washington
United States	Northwell Health/Center for Advanced Medicine	Lake Success	New York
United States	Saint Anthony Hospital	Lakewood	Colorado
United States	Alliance for Childhood Diseases/Cure 4 the Kids Foundation	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Central Valley	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Northwest	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada - Town Center	Las Vegas	Nevada
United States	Comprehensive Cancer Centers of Nevada-Summerlin	Las Vegas	Nevada
United States	GenesisCare USA - Las Vegas	Las Vegas	Nevada
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	Radiation Oncology Centers of Nevada Central	Las Vegas	Nevada
United States	Radiation Oncology Centers of Nevada Southeast	Las Vegas	Nevada
United States	Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center	Lebanon	New Hampshire
United States	Saint Joseph Hospital East	Lexington	Kentucky
United States	Saint Joseph Radiation Oncology Resource Center	Lexington	Kentucky
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Longmont United Hospital	Longmont	Colorado
United States	PeaceHealth Saint John Medical Center	Longview	Washington
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	Jewish Hospital	Louisville	Kentucky
United States	UofL Health Medical Center Northeast	Louisville	Kentucky
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Solinsky Center for Cancer Care	Manchester	New Hampshire
United States	Fairview Clinics and Surgery Center Maple Grove	Maple Grove	Minnesota
United States	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota
United States	Saint John's Hospital - Healtheast	Maplewood	Minnesota
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Idaho Urologic Institute-Meridian	Meridian	Idaho
United States	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho
United States	Garnet Health Medical Center	Middletown	New York
United States	Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Community Medical Hospital	Missoula	Montana
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Mobile Infirmary Medical Center	Mobile	Alabama
United States	Monticello Cancer Center	Monticello	Minnesota
United States	Northern Westchester Hospital	Mount Kisco	New York
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Saint Alphonsus Cancer Care Center-Nampa	Nampa	Idaho
United States	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho
United States	Vanderbilt Breast Center at One Hundred Oaks	Nashville	Tennessee
United States	Vanderbilt University/Ingram Cancer Center	Nashville	Tennessee
United States	Cancer Center of Western Wisconsin	New Richmond	Wisconsin
United States	Lenox Hill Hospital	New York	New York
United States	Manhattan Eye Ear and Throat Hospital	New York	New York
United States	Helen F Graham Cancer Center	Newark	Delaware
United States	Medical Oncology Hematology Consultants PA	Newark	Delaware
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	Cancer Care Center of O'Fallon	O'Fallon	Illinois
United States	Mercy Hospital Oklahoma City	Oklahoma City	Oklahoma
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska
United States	Alegent Health Immanuel Medical Center	Omaha	Nebraska
United States	Alegent Health Lakeside Hospital	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California
United States	AdventHealth Orlando	Orlando	Florida
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Parker Adventist Hospital	Parker	Colorado
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	OSF Saint Francis Radiation Oncology at Peoria Cancer Center	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Valley Radiation Oncology	Peru	Illinois
United States	Cancer Center at Saint Joseph's	Phoenix	Arizona
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Kootenai Clinic Cancer Services - Post Falls	Post Falls	Idaho
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Saint Mary Corwin Medical Center	Pueblo	Colorado
United States	Beebe Health Campus	Rehoboth Beach	Delaware
United States	Radiation Oncology Associates	Reno	Nevada
United States	Renown Regional Medical Center	Reno	Nevada
United States	Saint Mary's Regional Medical Center	Reno	Nevada
United States	Valley Medical Center	Renton	Washington
United States	North Memorial Medical Health Center	Robbinsdale	Minnesota
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri
United States	Norris Cotton Cancer Center-North	Saint Johnsbury	Vermont
United States	Heartland Regional Medical Center	Saint Joseph	Missouri
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Mercy Hospital South	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota
United States	Regions Hospital	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri
United States	Pacific Central Coast Health Center-San Luis Obispo	San Luis Obispo	California
United States	Mission Hope Medical Oncology - Santa Maria	Santa Maria	California
United States	Swedish Medical Center-Ballard Campus	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	PeaceHealth United General Medical Center	Sedro-Woolley	Washington
United States	Saint Francis Regional Medical Center	Shakopee	Minnesota
United States	Welch Cancer Center	Sheridan	Wyoming
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Baystate Medical Center	Springfield	Massachusetts
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Springfield Clinic	Springfield	Illinois
United States	Missouri Baptist Sullivan Hospital	Sullivan	Missouri
United States	BJC Outpatient Center at Sunset Hills	Sunset Hills	Missouri
United States	Saint Luke's Cancer Institute - Twin Falls	Twin Falls	Idaho
United States	Carle Cancer Center	Urbana	Illinois
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Providence Saint Mary Regional Cancer Center	Walla Walla	Washington
United States	Illinois CancerCare - Washington	Washington	Illinois
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Methodist West Hospital	West Des Moines	Iowa
United States	Rice Memorial Hospital	Willmar	Minnesota
United States	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota
United States	UMass Memorial Medical Center - University Campus	Worcester	Massachusetts
United States	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathological complete response		At the time of total mesorectal excision
Secondary	Rate of sphincter preservation in low-lying tumors	95% confidence interval will be estimated.	Up to 5 years
Secondary	Disease free survival	Kaplan-Meier method will be used.	Up to 5 years
Secondary	Overall survival	Kaplan-Meier method will be used.	Up to 5 years
Secondary	Incidence of adverse events	Will be assessed by Common Terminology Criteria for Adverse Events 5.0. Toxicities will be tabulated by grade and treatment relation.	Up to 5 years