Neoadjuvant Chemotherapy, Excision And Observation vs Chemoradiotherapy For Rectal Cancer

NCT06205485 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: CCTG-CO32NCI-2023-10515
• Study Type: interventional
• Target: 250
• Locations: 2 countries
• Sites: 109

Brief Summary

This study is being done to answer the following questions: Is the chance of rectal cancer responding the same if chemotherapy alone is given before limited surgery compared to chemotherapy and radiation therapy given together before limited surgery? If radiation therapy is not given, is quality of life better?

Conditions

Rectal Cancer

Outcome Measures

Primary Outcomes (2)

• Clinical response rate upon re-staging

  6 years

• Quality of Life defined using the LARS score

  6 years

Secondary Outcomes (11)

• Total Mesorectal Excision (TME) Free Survival

  6 years

• Disease Free Survival

  6 years

• Overall Survival

  6 years

• Rate of downstaging to ypTO/1N0/X

  6 years

• Bowel function assessed by Low Anterior Resection Syndrome (LARS) Score

  6 years

Study Arms (2)

FOLFOX OR CAPOX

ACTIVE COMPARATOR

FOLFOX= Six cycles of modified FOLFOX consisting of leucovorin, oxaliplatin and bolus fluoruracil (optional), infusional fluorouracil. CAPOX= Capecitabine twice daily for 14 days and Oxaliplatin on day 1

Drug: Leucovorin; Drug: Oxaliplatin; Drug: Fluoruracil; Drug: Capecitabine

ChemoRT

ACTIVE COMPARATOR

Standard dose of infusional 5-Fluorouracil/capecitabine and radiation

Drug: Fluoruracil; Drug: Capecitabine; Radiation: Radiation

Interventions

Leucovorin DRUG

400 mg/m2

FOLFOX OR CAPOX

Oxaliplatin DRUG

85 mg/m2 or 130 mg/m2 on day 1

FOLFOX OR CAPOX

Fluoruracil DRUG

bolus fluoruracil (optional) 400 mg, infusional fluorouracil 2,400 mg/m2

ChemoRT; FOLFOX OR CAPOX

Capecitabine DRUG

1,000 mg/m2 twice daily for 14 days

ChemoRT; FOLFOX OR CAPOX

Radiation RADIATION

54 Gy (27-30 fractions)

ChemoRT

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed invasive, well-moderately differentiated rectal adenocarcinoma, mismatch repair proficient.
• MRI stage cT1 not eligible for transanal surgery or cT2-T3ab\*. \* T3a: \<1mm depth invasion, T3b: 1-5mm depth of invasion.
• cN0 stage based on pelvic MRI - including absence of radiographic evidence of mesorectal nodal metastasis, tumour deposits or extramural venous invasion (EMVI).
• M0 stage based on no evidence of metastatic disease by CT imaging of chest, abdomen and pelvis.
• Mid to low-lying tumour eligible for transanal excision in the opinion of the treating surgeon.
• Medically fit to undergo radical TME surgery as per treating surgeon's decision.
• Participant is able (i.e. sufficiently fluent) and willing to complete the quality of life questionnaires in either English or French or Spanish.
• Age of at least 18 years.
• No contraindications to protocol chemotherapy.
• Adequate normal organ and marrow function: ANC ≥ x 10\^9/L; platelet count ≥ 100 x 10\^9/L; bilirubin \< 1.5 UNL, excluding Gilbert's syndrome; Estimated creatinine clearance of ≥ 50ml/min
• Patient must have an ECOG performance of \<2 (or Karnofsty ≥ 60%).
• Must be accessible for treatment and follow-up
• Males and females of reproductive potential must have agreed to use a highly effective contraceptive method during and for 6 months after completion of chemotherapy.
• HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.

You may not qualify if:

• Pathologic high-risk factors on diagnostic biopsy: high histologic grade (poorly differentiated), mucinous or signet ring histology.
• Patients with visible pelvic sidewall nodes on MRI.
• Patients with unequivocal determination of nodal disease that, in the opinion of the investigator, would prohibit protocol therapy administration.
• Previous pelvic radiation for any reason, including brachytherapy alone.
• Patients who have had primary lesion excised prior to enrollment. If a patient has had partial excision prior to enrollment, there must be gross residual disease endoscopically for patient to be eligible.
• 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.
• Prior treatment for rectal cancer.
• Patients with known dihydropyrimidine dehydrogenase deficiency (DYPD).
• Potential trial participants should have recovered from clinically significant adverse events of their most recent therapy/intervention prior to enrollment.
• 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.
• Any contra-indications to undergo MRI imaging.
• Presence of anterior lesions above or near peritoneal reflection rendering the patient ineligible for a transanal tumour excision.
• T3 tumours invading or abutting the internal sphincter.

Sponsors & Collaborators

• Canadian Cancer Trials Group: lead
• Alliance for Clinical Trials in Oncology: collaborator
• NRG Oncology: collaborator
• ECOG-ACRIN Cancer Research Group: collaborator
• SWOG Cancer Research Network: collaborator

Study Sites (109)

Cancer Center at Saint Joseph's

Phoenix, Arizona, 85004, United States

RECRUITING

UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

Irvine, California, 92612, United States

RECRUITING

Los Angeles General Medical Center

Los Angeles, California, 90033, United States

RECRUITING

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

RECRUITING

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

RECRUITING

Mission Hope Medical Oncology - Santa Maria

Santa Maria, California, 93444, United States

RECRUITING

Beebe South Coastal Health Campus

Millville, Delaware, 19967, United States

RECRUITING

Helen F Graham Cancer Center

Newark, Delaware, 19713, United States

RECRUITING

Medical Oncology Hematology Consultants PA

Newark, Delaware, 19713, United States

RECRUITING

Beebe Health Campus

Rehoboth Beach, Delaware, 19971, United States

RECRUITING

Orlando Health Cancer Institute

Orlando, Florida, 32806, United States

RECRUITING

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

RECRUITING

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

RECRUITING

Emory Saint Joseph's Hospital

Atlanta, Georgia, 30342, United States

RECRUITING

Rush-Copley Medical Center

Aurora, Illinois, 60504, United States

RECRUITING

Northwestern University

Chicago, Illinois, 60611, United States

RECRUITING

Carle at The Riverfront

Danville, Illinois, 61832, United States

RECRUITING

Northwestern Medicine Cancer Center Kishwaukee

DeKalb, Illinois, 60115, United States

RECRUITING

Carle Physician Group-Effingham

Effingham, Illinois, 62401, United States

RECRUITING

Northwestern Medicine Cancer Center Delnor

Geneva, Illinois, 60134, United States

RECRUITING

Carle Physician Group-Mattoon/Charleston

Mattoon, Illinois, 61938, United States

RECRUITING

Carle Cancer Center

Urbana, Illinois, 61801, United States

RECRUITING

Northwestern Medicine Cancer Center Warrenville

Warrenville, Illinois, 60555, United States

RECRUITING

Northwest Cancer Center - Crown Point

Crown Point, Indiana, 46307, United States

RECRUITING

Northwest Oncology LLC

Dyer, Indiana, 46311, United States

RECRUITING

Northwest Cancer Center - Hobart

Hobart, Indiana, 46342, United States

RECRUITING

Saint Mary Medical Center

Hobart, Indiana, 46342, United States

RECRUITING

The Community Hospital

Munster, Indiana, 46321, United States

RECRUITING

Northwest Cancer Center - Valparaiso

Valparaiso, Indiana, 46383, United States

RECRUITING

University Medical Center New Orleans

New Orleans, Louisiana, 70112, United States

RECRUITING

Beverly Hospital

Beverly, Massachusetts, 01915, United States

RECRUITING

Lahey Hospital and Medical Center

Burlington, Massachusetts, 01805, United States

RECRUITING

Addison Gilbert Hospital

Gloucester, Massachusetts, 01930, United States

RECRUITING

Henry Ford Cancer Institute-Downriver

Brownstown, Michigan, 48183, United States

RECRUITING

Henry Ford Macomb Hospital-Clinton Township

Clinton Township, Michigan, 48038, United States

RECRUITING

Henry Ford Medical Center-Fairlane

Dearborn, Michigan, 48126, United States

RECRUITING

Henry Ford Hospital

Detroit, Michigan, 48202, United States

RECRUITING

Corewell Health Grand Rapids Hospitals - Butterworth Hospital

Grand Rapids, Michigan, 49503, United States

RECRUITING

Allegiance Health

Jackson, Michigan, 49201, United States

RECRUITING

West Michigan Cancer Center

Kalamazoo, Michigan, 49007, United States

RECRUITING

Henry Ford Medical Center-Columbus

Novi, Michigan, 48377, United States

RECRUITING

Henry Ford West Bloomfield Hospital

West Bloomfield, Michigan, 48322, United States

RECRUITING

Henry Ford Wyandotte Hospital

Wyandotte, Michigan, 48192, United States

RECRUITING

Sanford Joe Lueken Cancer Center

Bemidji, Minnesota, 56601, United States

RECRUITING

Mercy Hospital Saint Louis

St Louis, Missouri, 63141, United States

RECRUITING

Renown Regional Medical Center

Reno, Nevada, 89502, United States

RECRUITING

Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

Lebanon, New Hampshire, 03756, United States

RECRUITING

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

RECRUITING

University of New Mexico Cancer Center

Albuquerque, New Mexico, 87106, United States

RECRUITING

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

RECRUITING

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

University of Rochester

Rochester, New York, 14642, United States

RECRUITING

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

RECRUITING

Wilmot Cancer Institute at Webster

Webster, New York, 14580, United States

RECRUITING

East Carolina University

Greenville, North Carolina, 27834, United States

RECRUITING

Sanford Bismarck Medical Center

Bismarck, North Dakota, 58501, United States

RECRUITING

Sanford Broadway Medical Center

Fargo, North Dakota, 58122, United States

RECRUITING

Sanford Roger Maris Cancer Center

Fargo, North Dakota, 58122, United States

RECRUITING

Miami Valley Hospital South

Centerville, Ohio, 45459, United States

RECRUITING

University of Cincinnati Cancer Center-UC Medical Center

Cincinnati, Ohio, 45219, United States

RECRUITING

Miami Valley Hospital

Dayton, Ohio, 45409, United States

SUSPENDED

Premier Blood and Cancer Center

Dayton, Ohio, 45409, United States

RECRUITING

Miami Valley Hospital North

Dayton, Ohio, 45415, United States

RECRUITING

Atrium Medical Center-Middletown Regional Hospital

Franklin, Ohio, 45005-1066, United States

RECRUITING

Miami Valley Cancer Care and Infusion

Greenville, Ohio, 45331, United States

RECRUITING

Upper Valley Medical Center

Troy, Ohio, 45373, United States

RECRUITING

University of Cincinnati Cancer Center-West Chester

West Chester, Ohio, 45069, United States

RECRUITING

Clackamas Radiation Oncology Center

Clackamas, Oregon, 97015, United States

RECRUITING

Legacy Mount Hood Medical Center

Gresham, Oregon, 97030, United States

RECRUITING

Providence Newberg Medical Center

Newberg, Oregon, 97132, United States

RECRUITING

Providence Willamette Falls Medical Center

Oregon City, Oregon, 97045, United States

RECRUITING

Legacy Good Samaritan Hospital and Medical Center

Portland, Oregon, 97210, United States

RECRUITING

Providence Portland Medical Center

Portland, Oregon, 97213, United States

RECRUITING

Providence Saint Vincent Medical Center

Portland, Oregon, 97225, United States

RECRUITING

Oregon Health and Science University

Portland, Oregon, 97239, United States

RECRUITING

Legacy Meridian Park Hospital

Tualatin, Oregon, 97062, United States

RECRUITING

Christiana Care Health System-Concord Health Center

Chadds Ford, Pennsylvania, 19317, United States

RECRUITING

Sanford Cancer Center Oncology Clinic

Sioux Falls, South Dakota, 57104, United States

RECRUITING

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota, 57117-5134, United States

RECRUITING

The West Clinic - Wolf River

Germantown, Tennessee, 38138, United States

RECRUITING

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

RECRUITING

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Scott and White Memorial Hospital

Temple, Texas, 76508, United States

RECRUITING

Dartmouth Cancer Center - North

Saint Johnsbury, Vermont, 05819, United States

RECRUITING

FHCC Overlake

Bellevue, Washington, 98004, United States

RECRUITING

FHCC at EvergreenHealth

Kirkland, Washington, 98034, United States

RECRUITING

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

RECRUITING

FHCC at Northwest Hospital

Seattle, Washington, 98133, United States

RECRUITING

Legacy Cancer Institute Medical Oncology and Day Treatment

Vancouver, Washington, 98684, United States

RECRUITING

Legacy Salmon Creek Hospital

Vancouver, Washington, 98686, United States

RECRUITING

Marshfield Medical Center-EC Cancer Center

Eau Claire, Wisconsin, 54701, United States

RECRUITING

Marshfield Medical Center-Marshfield

Marshfield, Wisconsin, 54449, United States

RECRUITING

Marshfield Medical Center - Minocqua

Minocqua, Wisconsin, 54548, United States

RECRUITING

Marshfield Medical Center-Rice Lake

Rice Lake, Wisconsin, 54868, United States

RECRUITING

Marshfield Medical Center-River Region at Stevens Point

Stevens Point, Wisconsin, 54482, United States

RECRUITING

Marshfield Medical Center - Weston

Weston, Wisconsin, 54476, United States

RECRUITING

BCCA-Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

RECRUITING

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

RECRUITING

Doctor H. Bliss Murphy Cancer Centre

St. John's, Newfoundland and Labrador, A1B 3V6, Canada

RECRUITING

London Regional Cancer Program

London, Ontario, N6A 4L6, Canada

RECRUITING

Ottawa Hospital and Cancer Center-General Campus

Ottawa, Ontario, K1H 8L6, Canada

RECRUITING

CIUSSSEMTL-Hopital Maisonneuve-Rosemont

Montreal, Quebec, H1T 2M4, Canada

RECRUITING

Allan Blair Cancer Centre

Regina, Saskatchewan, S4T 7T1, Canada

RECRUITING

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, S7N 4H4, Canada

RECRUITING

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Leucovorin; Oxaliplatin; Fluorouracil; Capecitabine; Radiation

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Physical Phenomena

Study Officials

• Hagen Kennecke

  Providence Portland Medical Centre, Portland, OR, USA

  STUDY CHAIR

• Carl Brown

  St. Paul's Hospital, Vancouver, BC, Canada

  STUDY CHAIR

Central Study Contacts

Chris O'Callaghan

CONTACT

613-533-6430; cocallaghan@ctg.queensu.ca

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2023
• First Posted: January 16, 2024
• Study Start: June 26, 2024
• Primary Completion (Estimated): January 30, 2030
• Study Completion (Estimated): June 30, 2030
• Last Updated: June 9, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (8); US (101)