Neoadjuvant Chemotherapy, Excision And Observation vs Chemoradiotherapy For Rectal Cancer
- Conditions
- Rectal Cancer
- Interventions
- Registration Number
- NCT06205485
- Lead Sponsor
- Canadian Cancer Trials Group
- 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?
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 250
- Histologically confirmed invasive, well-moderately differentiated rectal adenocarcinoma, mismatch repair proficient.
- MRI stage cT1 not eligible for transanal surgery or cT2.
- 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
- Women/men of childbearing 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.
- Pathologic high-risk factors on diagnostic biopsy: high histologic grade (poorly differentiated), mucinous or signet ring histology, lymphatic/vascular or perineural invasion.
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ChemoRT Fluoruracil Standard dose of infusional 5-Fluorouracil/capecitabine and radiation ChemoRT Capecitabine Standard dose of infusional 5-Fluorouracil/capecitabine and radiation ChemoRT Radiation Standard dose of infusional 5-Fluorouracil/capecitabine and radiation FOLFOX OR CAPOX Leucovorin 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 FOLFOX OR CAPOX Oxaliplatin 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 FOLFOX OR CAPOX Fluoruracil 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 FOLFOX OR CAPOX Capecitabine 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
- Primary Outcome Measures
Name Time Method Clinical response rate upon re-staging 6 years Quality of Life defined using the LARS score 6 years
- Secondary Outcome Measures
Name Time Method Rate of downstaging to ypTO/1N0/X 6 years Bowel function assessed by Low Anterior Resection Syndrome (LARS) Score 6 years Bladder function assessed by EORTC QLQ-CR29 urinary frequency and urinary incontinence subscales 6 years Sexual function assessed by EORTC QLQ-CR29 sexual interest (men), and sexual interest (women) subscales 6 years Total Mesorectal Excision (TME) Free Survival 6 years Defined as time from randomization to the time of TME attempt or performance, local recurrence after complete clinical response (cCR), or death from any cause
Disease Free Survival 6 years Defined as time from randomization to local recurrence/regrowth after cCR that cannot be salvaged with an R0 TM, M1 recurrence, or death
Other QoL functions assessed by subscales of FIQL 6 years Other QoL functions assessed by subscales of EORTC QLQ-C30 6 years Other QoL functions assessed by subscales of subscales of EORTC QLQ-CR29 6 years Number and severity of adverse events utilizing CTCAE v5.0 6 years Validate the magnetic resonance tumour regression grade (MR-TRG) in patients with T1 and T2 rectal cancer 6 years
Trial Locations
- Locations (68)
Cancer Center at Saint Joseph's
🇺🇸Phoenix, Arizona, United States
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
🇺🇸Irvine, California, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
🇺🇸Orange, California, United States
Beebe South Coastal Health Campus
🇺🇸Millville, Delaware, United States
Helen F Graham Cancer Center
🇺🇸Newark, Delaware, United States
Medical Oncology Hematology Consultants PA
🇺🇸Newark, Delaware, United States
Beebe Health Campus
🇺🇸Rehoboth Beach, Delaware, United States
Emory University Hospital Midtown
🇺🇸Atlanta, Georgia, United States
Emory University Hospital/Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
Emory Saint Joseph's Hospital
🇺🇸Atlanta, Georgia, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Carle at The Riverfront
🇺🇸Danville, Illinois, United States
Carle Physician Group-Effingham
🇺🇸Effingham, Illinois, United States
Carle Physician Group-Mattoon/Charleston
🇺🇸Mattoon, Illinois, United States
Carle Cancer Center
🇺🇸Urbana, Illinois, United States
Northwest Cancer Center - Main Campus
🇺🇸Crown Point, Indiana, United States
Northwest Oncology LLC
🇺🇸Dyer, Indiana, United States
Northwest Cancer Center - Hobart
🇺🇸Hobart, Indiana, United States
Saint Mary Medical Center
🇺🇸Hobart, Indiana, United States
The Community Hospital
🇺🇸Munster, Indiana, United States
Northwest Cancer Center - Valparaiso
🇺🇸Valparaiso, Indiana, United States
University Medical Center New Orleans
🇺🇸New Orleans, Louisiana, United States
Corewell Health Grand Rapids Hospitals - Butterworth Hospital
🇺🇸Grand Rapids, Michigan, United States
West Michigan Cancer Center
🇺🇸Kalamazoo, Michigan, United States
Sanford Joe Lueken Cancer Center
🇺🇸Bemidji, Minnesota, United States
Renown Regional Medical Center
🇺🇸Reno, Nevada, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
🇺🇸Lebanon, New Hampshire, United States
University of New Mexico Cancer Center
🇺🇸Albuquerque, New Mexico, United States
Sanford Bismarck Medical Center
🇺🇸Bismarck, North Dakota, United States
Sanford Broadway Medical Center
🇺🇸Fargo, North Dakota, United States
Sanford Roger Maris Cancer Center
🇺🇸Fargo, North Dakota, United States
Miami Valley Hospital South
🇺🇸Centerville, Ohio, United States
University of Cincinnati Cancer Center-UC Medical Center
🇺🇸Cincinnati, Ohio, United States
Miami Valley Hospital
🇺🇸Dayton, Ohio, United States
Premier Blood and Cancer Center
🇺🇸Dayton, Ohio, United States
Miami Valley Hospital North
🇺🇸Dayton, Ohio, United States
Atrium Medical Center-Middletown Regional Hospital
🇺🇸Franklin, Ohio, United States
Miami Valley Cancer Care and Infusion
🇺🇸Greenville, Ohio, United States
Upper Valley Medical Center
🇺🇸Troy, Ohio, United States
University of Cincinnati Cancer Center-West Chester
🇺🇸West Chester, Ohio, United States
Clackamas Radiation Oncology Center
🇺🇸Clackamas, Oregon, United States
Legacy Mount Hood Medical Center
🇺🇸Gresham, Oregon, United States
Providence Newberg Medical Center
🇺🇸Newberg, Oregon, United States
Providence Willamette Falls Medical Center
🇺🇸Oregon City, Oregon, United States
Legacy Good Samaritan Hospital and Medical Center
🇺🇸Portland, Oregon, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
Providence Saint Vincent Medical Center
🇺🇸Portland, Oregon, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Legacy Meridian Park Hospital
🇺🇸Tualatin, Oregon, United States
Christiana Care Health System-Concord Health Center
🇺🇸Chadds Ford, Pennsylvania, 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
The West Clinic - Wolf River
🇺🇸Germantown, Tennessee, United States
Vanderbilt University/Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Dartmouth Cancer Center - North
🇺🇸Saint Johnsbury, Vermont, United States
Virginia Mason Medical Center
🇺🇸Seattle, Washington, United States
Legacy Cancer Institute Medical Oncology and Day Treatment
🇺🇸Vancouver, Washington, United States
Legacy Salmon Creek Hospital
🇺🇸Vancouver, Washington, United States
Marshfield Medical Center-EC Cancer Center
🇺🇸Eau Claire, Wisconsin, United States
Marshfield Medical Center-Marshfield
🇺🇸Marshfield, Wisconsin, United States
Marshfield Medical Center - Minocqua
🇺🇸Minocqua, Wisconsin, United States
Marshfield Medical Center-Rice Lake
🇺🇸Rice Lake, Wisconsin, United States
Marshfield Medical Center-River Region at Stevens Point
🇺🇸Stevens Point, Wisconsin, United States
Marshfield Medical Center - Weston
🇺🇸Weston, Wisconsin, United States
CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
Ottawa Hospital and Cancer Center-General Campus
🇨🇦Ottawa, Ontario, Canada
Allan Blair Cancer Centre
🇨🇦Regina, Saskatchewan, Canada
Saskatoon Cancer Centre
🇨🇦Saskatoon, Saskatchewan, Canada