Clinical trial NCT06205485: Neoadjuvant Chemotherapy, Excision And Observation vs Chemoradiotherapy For Rectal Cancer
Official title: A Phase 3 Randomized Trial Of Neoadjuvant Chemotherapy, Excision And Observation Versus Chemoradiotherapy For Early Rectal Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Rectal Cancer
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
Collaborators: name: Alliance for Clinical Trials in Oncology
name: ECOG-ACRIN Cancer Research Group
name: NRG Oncology
name: SWOG Cancer Research Network
First posted: 2024-01-16
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed invasive, well-moderately differentiated rectal adenocarcinoma, mismatch repair proficient.
* MRI stage cT1 not eligible for transanal surgery or cT2-T3a.
* 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.

Primary outcomes:
measure: Clinical response rate upon re-staging
timeFrame: 6 years
measure: Quality of Life defined using the LARS score
timeFrame: 6 years
Secondary outcomes:
measure: Total Mesorectal Excision (TME) Free Survival
timeFrame: 6 years
measure: Disease Free Survival
timeFrame: 6 years
measure: Overall Survival
timeFrame: 6 years
measure: Rate of downstaging to ypTO/1N0/X
timeFrame: 6 years
measure: Bowel function assessed by Low Anterior Resection Syndrome (LARS) Score
timeFrame: 6 years
measure: Bladder function assessed by EORTC QLQ-CR29 urinary frequency and urinary incontinence subscales
timeFrame: 6 years
measure: Other QoL functions assessed by subscales of FIQL
timeFrame: 6 years
measure: Other QoL functions assessed by subscales of EORTC QLQ-C30
timeFrame: 6 years
measure: Other QoL functions assessed by subscales of subscales of EORTC QLQ-CR29
timeFrame: 6 years
measure: Number and severity of adverse events utilizing CTCAE v5.0
timeFrame: 6 years
measure: Validate the magnetic resonance tumour regression grade (MR-TRG) in patients with T1-T3a rectal cancer
timeFrame: 6 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Cancer Center at Saint Joseph's
state: Arizona
city: Irvine
country: United States
facility: UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
state: California
city: Orange
country: United States
facility: UC Irvine Health/Chao Family Comprehensive Cancer Center
state: California
city: Millville
country: United States
facility: Beebe South Coastal Health Campus
state: Delaware
city: Newark
country: United States
facility: Helen F Graham Cancer Center
state: Delaware
city: Newark
country: United States
facility: Medical Oncology Hematology Consultants PA
state: Delaware
city: Rehoboth Beach
country: United States
facility: Beebe Health Campus
state: Delaware
city: Atlanta
country: United States
facility: Emory University Hospital Midtown
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital/Winship Cancer Institute
state: Georgia
city: Atlanta
country: United States
facility: Emory Saint Joseph's Hospital
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Danville
country: United States
facility: Carle at The Riverfront
state: Illinois
city: Effingham
country: United States
facility: Carle Physician Group-Effingham
state: Illinois
city: Mattoon
country: United States
facility: Carle Physician Group-Mattoon/Charleston
state: Illinois
city: Urbana
country: United States
facility: Carle Cancer Center
state: Illinois
city: Crown Point
country: United States
facility: Northwest Cancer Center - Main Campus
state: Indiana
city: Dyer
country: United States
facility: Northwest Oncology LLC
state: Indiana
city: Hobart
country: United States
facility: Northwest Cancer Center - Hobart
state: Indiana
city: Hobart
country: United States
facility: Saint Mary Medical Center
state: Indiana
city: Munster
country: United States
facility: The Community Hospital
state: Indiana
city: Valparaiso
country: United States
facility: Northwest Cancer Center - Valparaiso
state: Indiana
city: New Orleans
country: United States
facility: University Medical Center New Orleans
state: Louisiana
city: Grand Rapids
country: United States
facility: Corewell Health Grand Rapids Hospitals - Butterworth Hospital
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Bemidji
country: United States
facility: Sanford Joe Lueken Cancer Center
state: Minnesota
city: Reno
country: United States
facility: Renown Regional Medical Center
state: Nevada
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
state: New Hampshire
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: Bismarck
country: United States
facility: Sanford Bismarck Medical Center
state: North Dakota
city: Fargo
country: United States
facility: Sanford Broadway Medical Center
state: North Dakota
city: Fargo
country: United States
facility: Sanford Roger Maris Cancer Center
state: North Dakota
city: Centerville
country: United States
facility: Miami Valley Hospital South
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati Cancer Center-UC Medical Center
state: Ohio
city: Dayton
country: United States
facility: Miami Valley Hospital
state: Ohio
city: Dayton
country: United States
facility: Premier Blood and Cancer Center
state: Ohio
city: Dayton
country: United States
facility: Miami Valley Hospital North
state: Ohio
city: Franklin
country: United States
facility: Atrium Medical Center-Middletown Regional Hospital
state: Ohio
city: Greenville
country: United States
facility: Miami Valley Cancer Care and Infusion
state: Ohio
city: Troy
country: United States
facility: Upper Valley Medical Center
state: Ohio
city: West Chester
country: United States
facility: University of Cincinnati Cancer Center-West Chester
state: Ohio
city: Clackamas
country: United States
facility: Clackamas Radiation Oncology Center
state: Oregon
city: Gresham
country: United States
facility: Legacy Mount Hood Medical Center
state: Oregon
city: Newberg
country: United States
facility: Providence Newberg Medical Center
state: Oregon
city: Oregon City
country: United States
facility: Providence Willamette Falls Medical Center
state: Oregon
city: Portland
country: United States
facility: Legacy Good Samaritan Hospital and Medical Center
state: Oregon
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Portland
country: United States
facility: Providence Saint Vincent Medical Center
state: Oregon
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Tualatin
country: United States
facility: Legacy Meridian Park Hospital
state: Oregon
city: Chadds Ford
country: United States
facility: Christiana Care Health System-Concord Health Center
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Sanford Cancer Center Oncology Clinic
state: South Dakota
city: Sioux Falls
country: United States
facility: Sanford USD Medical Center - Sioux Falls
state: South Dakota
city: Germantown
country: United States
facility: The West Clinic - Wolf River
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University/Ingram Cancer Center
state: Tennessee
city: Saint Johnsbury
country: United States
facility: Dartmouth Cancer Center - North
state: Vermont
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Vancouver
country: United States
facility: Legacy Cancer Institute Medical Oncology and Day Treatment
state: Washington
city: Vancouver
country: United States
facility: Legacy Salmon Creek Hospital
state: Washington
city: Eau Claire
country: United States
facility: Marshfield Medical Center-EC Cancer Center
state: Wisconsin
city: Marshfield
country: United States
facility: Marshfield Medical Center-Marshfield
state: Wisconsin
city: Minocqua
country: United States
facility: Marshfield Medical Center - Minocqua
state: Wisconsin
city: Rice Lake
country: United States
facility: Marshfield Medical Center-Rice Lake
state: Wisconsin
city: Stevens Point
country: United States
facility: Marshfield Medical Center-River Region at Stevens Point
state: Wisconsin
city: Weston
country: United States
facility: Marshfield Medical Center - Weston
state: Wisconsin
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Ottawa
country: Canada
facility: Ottawa Hospital and Cancer Center-General Campus
state: Ontario
city: Regina
country: Canada
facility: Allan Blair Cancer Centre
state: Saskatchewan
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre
state: Saskatchewan
Study officials:
affiliation: Providence Portland Medical Centre, Portland, OR, USA
name: Hagen Kennecke
role: STUDY_CHAIR
affiliation: St. Paul's Hospital, Vancouver, BC, Canada
name: Carl Brown
role: STUDY_CHAIR
References: