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NCT06205485PHASE3Recruiting

Neoadjuvant Chemotherapy, Excision And Observation vs Chemoradiotherapy For Rectal Cancer

Canadian Cancer Trials Group

Start Date

6/26/2024

Completion Date

6/30/2030

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?

Detailed Description

This study is being done to find out if this approach is better or worse than the usual approach for early rectal cancer. The usual approach is defined as care most people get for early rectal cancer. The usual approach for patients who are not in a study is surgery to remove the rectum or treatment with chemotherapy and radiation therapy, followed by surgery. There are several chemotherapy drugs approved by Health Canada that are commonly used with radiation therapy. For patients who get the usual approach for this cancer, about 90 out of 100 are free of cancer after 5 years. If a patient decides to take part in this study, they will either get a combination of chemotherapy drugs called FOLFOX or CAPOX for up to 12 weeks or will get chemotherapy with radiation therapy for up to 6 weeks. After finishing treatment, and even if treatment is stopped early, the study doctor will watch for side effects and determine which type of surgery would be best. After surgery, patients will be asked to come in every 4 months for 2 years, then every 6 months for an additional year. Then will be checked every year for 2 years. This means seeing the study doctor for up to 5 years after surgery. Patients may be seen more often if your study doctor thinks it is necessary.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: * 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. Exclusion Criteria: * 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.

Interventions

DRUG

Leucovorin

DRUG

Oxaliplatin

DRUG

Fluoruracil

DRUG

Capecitabine

RADIATION

Radiation

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Conditions

Rectal Cancer

Locations

Cancer Center at Saint Joseph's

Phoenix, Arizona 85004

United States

UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

Irvine, California 92612

United States

Los Angeles General Medical Center

Los Angeles, California 90033

United States

USC / Norris Comprehensive Cancer Center

Los Angeles, California 90033

United States

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California 92868

United States

Mission Hope Medical Oncology - Santa Maria

Santa Maria, California 93444

United States

Beebe South Coastal Health Campus

Millville, Delaware 19967

United States

Helen F Graham Cancer Center

Newark, Delaware 19713

United States

Medical Oncology Hematology Consultants PA

Newark, Delaware 19713

United States

Beebe Health Campus

Rehoboth Beach, Delaware 19971

United States

Orlando Health Cancer Institute

Orlando, Florida 32806

United States

Emory University Hospital Midtown

Atlanta, Georgia 30308

United States

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia 30322

United States

Emory Saint Joseph's Hospital

Atlanta, Georgia 30342

United States

Rush-Copley Medical Center

Aurora, Illinois 60504

United States

Northwestern University

Chicago, Illinois 60611

United States

Carle at The Riverfront

Danville, Illinois 61832

United States

Northwestern Medicine Cancer Center Kishwaukee

DeKalb, Illinois 60115

United States

Carle Physician Group-Effingham

Effingham, Illinois 62401

United States

Northwestern Medicine Cancer Center Delnor

Geneva, Illinois 60134

United States

Carle Physician Group-Mattoon/Charleston

Mattoon, Illinois 61938

United States

Carle Cancer Center

Urbana, Illinois 61801

United States

Northwestern Medicine Cancer Center Warrenville

Warrenville, Illinois 60555

United States

Northwest Cancer Center - Crown Point

Crown Point, Indiana 46307

United States

Northwest Oncology LLC

Dyer, Indiana 46311

United States

Northwest Cancer Center - Hobart

Hobart, Indiana 46342

United States

Saint Mary Medical Center

Hobart, Indiana 46342

United States

The Community Hospital

Munster, Indiana 46321

United States

Northwest Cancer Center - Valparaiso

Valparaiso, Indiana 46383

United States

Ochsner Hematology Oncology North Shore - Covington (West Region)

Covington, Louisiana 70433

United States

University Medical Center New Orleans

New Orleans, Louisiana 70112

United States

Ochsner Medical Center Jefferson

New Orleans, Louisiana 70121

United States

Beverly Hospital

Beverly, Massachusetts 01915

United States

Lahey Clinic

Burlington, Massachusetts 01805

United States

Addison Gilbert Hospital

Gloucester, Massachusetts 01930

United States

Henry Ford Cancer Institute-Downriver

Brownstown, Michigan 48183

United States

Henry Ford Macomb Hospital-Clinton Township

Clinton Township, Michigan 48038

United States

Henry Ford Medical Center-Fairlane

Dearborn, Michigan 48126

United States

Henry Ford Hospital

Detroit, Michigan 48202

United States

Corewell Health Grand Rapids Hospitals - Butterworth Hospital

Grand Rapids, Michigan 49503

United States

Allegiance Health

Jackson, Michigan 49201

United States

West Michigan Cancer Center

Kalamazoo, Michigan 49007

United States

Henry Ford Medical Center-Columbus

Novi, Michigan 48377

United States

Henry Ford West Bloomfield Hospital

West Bloomfield, Michigan 48322

United States

Henry Ford Wyandotte Hospital

Wyandotte, Michigan 48192

United States

Sanford Joe Lueken Cancer Center

Bemidji, Minnesota 56601

United States

Mercy Hospital Saint Louis

St Louis, Missouri 63141

United States

Renown Regional Medical Center

Reno, Nevada 89502

United States

Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

Lebanon, New Hampshire 03756

United States

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey 07920

United States

Memorial Sloan Kettering Monmouth

Middletown, New Jersey 07748

United States

Memorial Sloan Kettering Bergen

Montvale, New Jersey 07645

United States

University of New Mexico Cancer Center

Albuquerque, New Mexico 87106

United States

Roswell Park Cancer Institute

Buffalo, New York 14263

United States

Memorial Sloan Kettering Commack

Commack, New York 11725

United States

Memorial Sloan Kettering Westchester

Harrison, New York 10604

United States

Memorial Sloan Kettering Cancer Center

New York, New York 10065

United States

University of Rochester

Rochester, New York 14642

United States

Memorial Sloan Kettering Nassau

Uniondale, New York 11553

United States

Wilmot Cancer Institute at Webster

Webster, New York 14580

United States

East Carolina University

Greenville, North Carolina 27834

United States

Sanford Bismarck Medical Center

Bismarck, North Dakota 58501

United States

Sanford Broadway Medical Center

Fargo, North Dakota 58122

United States

Sanford Roger Maris Cancer Center

Fargo, North Dakota 58122

United States

Miami Valley Hospital South

Centerville, Ohio 45459

United States

University of Cincinnati Cancer Center-UC Medical Center

Cincinnati, Ohio 45219

United States

Ohio State University Comprehensive Cancer Center

Columbus, Ohio 43210

United States

Miami Valley Hospital

Dayton, Ohio 45409

United States

Premier Blood and Cancer Center

Dayton, Ohio 45409

United States

Miami Valley Hospital North

Dayton, Ohio 45415

United States

Atrium Medical Center-Middletown Regional Hospital

Franklin, Ohio 45005-1066

United States

Miami Valley Cancer Care and Infusion

Greenville, Ohio 45331

United States

Upper Valley Medical Center

Troy, Ohio 45373

United States

University of Cincinnati Cancer Center-West Chester

West Chester, Ohio 45069

United States

Clackamas Radiation Oncology Center

Clackamas, Oregon 97015

United States

Legacy Mount Hood Medical Center

Gresham, Oregon 97030

United States

Providence Newberg Medical Center

Newberg, Oregon 97132

United States

Providence Willamette Falls Medical Center

Oregon City, Oregon 97045

United States

Legacy Good Samaritan Hospital and Medical Center

Portland, Oregon 97210

United States

Providence Portland Medical Center

Portland, Oregon 97213

United States

Providence Saint Vincent Medical Center

Portland, Oregon 97225

United States

Oregon Health and Science University

Portland, Oregon 97239

United States

Legacy Meridian Park Hospital

Tualatin, Oregon 97062

United States

Christiana Care Health System-Concord Health Center

Chadds Ford, Pennsylvania 19317

United States

Penn State Milton S Hershey Medical Center

Hershey, Pennsylvania 17033-0850

United States

Sanford Cancer Center Oncology Clinic

Sioux Falls, South Dakota 57104

United States

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota 57117-5134

United States

The West Clinic - Wolf River

Germantown, Tennessee 38138

United States

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee 37232

United States

UT MD Anderson Cancer Center

Houston, Texas 77030

United States

Scott and White Memorial Hospital

Temple, Texas 76508

United States

Dartmouth Cancer Center - North

Saint Johnsbury, Vermont 05819

United States

FHCC Overlake

Bellevue, Washington 98004

United States

FHCC at EvergreenHealth

Kirkland, Washington 98034

United States

Virginia Mason Medical Center

Seattle, Washington 98101

United States

Fred Hutchinson Cancer Center

Seattle, Washington 98109

United States

FHCC at Northwest Hospital

Seattle, Washington 98133

United States

Legacy Cancer Institute Medical Oncology and Day Treatment

Vancouver, Washington 98684

United States

Legacy Salmon Creek Hospital

Vancouver, Washington 98686

United States

Marshfield Medical Center-EC Cancer Center

Eau Claire, Wisconsin 54701

United States

Marshfield Medical Center-Marshfield

Marshfield, Wisconsin 54449

United States

Marshfield Medical Center - Minocqua

Minocqua, Wisconsin 54548

United States

Marshfield Medical Center-Rice Lake

Rice Lake, Wisconsin 54868

United States

Marshfield Medical Center-River Region at Stevens Point

Stevens Point, Wisconsin 54482

United States

Marshfield Medical Center - Weston

Weston, Wisconsin 54476

United States

BCCA-Vancouver Cancer Centre

Vancouver, British Columbia V5Z 4E6

Canada

CancerCare Manitoba

Winnipeg, Manitoba R3E 0V9

Canada

Doctor H. Bliss Murphy Cancer Centre

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

Canada

London Regional Cancer Program

London, Ontario N6A 4L6

Canada

Ottawa Hospital and Cancer Center-General Campus

Ottawa, Ontario K1H 8L6

Canada

CIUSSSEMTL-Hopital Maisonneuve-Rosemont

Montreal, Quebec H1T 2M4

Canada

Allan Blair Cancer Centre

Regina, Saskatchewan S4T 7T1

Canada

Saskatoon Cancer Centre

Saskatoon, Saskatchewan S7N 4H4

Canada