NEO: Neoadjuvant Chemotherapy, Excision and Observation for Early Rectal Cancer

Phase 2

Completed

Conditions: Rectal Cancer

Interventions: Drug: Folfox Protocol
Drug: Capox

Registration Number: NCT03259035

Lead Sponsor: Canadian Cancer Trials Group

Brief Summary: The purpose of this study is to find out the effects of chemotherapy followed by less invasive surgery on patients and their early rectal cancer. The approach of this trial will be considered a success if at least 65% of participants are able to keep the rectum.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 58

Inclusion Criteria

Histologically confirmed invasive well-moderately differentiated rectal adenocarcinoma diagnosed within 90 days prior to enrollment.
Tumour stage cT1-T3abN0 based on pelvic MRI
- cT1N0- tumour invasion into submucosa, no radiographic evidence of mesorectal nodal metastasis, tumour deposits or vascular invasion.
- cT2N0 - tumour invasion into muscularis propria, no radiographic evidence of mesorectal nodal metastasis, tumour deposits or vascular invasion.
- cT3a,bN0- tumour invasion through the muscularis propria no more than 5 mm into the subserosa/perirectal tissue and clear of the circumferential radial margin (CRM). Absence of radiographic evidence of mesorectal nodal metastasis, tumour deposits or lymphovascular invasion.

Note: If the tumour is not visualized in the MRI but there is histological confirmation of rectal adenocarcinoma the patient is eligible.

cN0 stage based on pelvic MRI. Any nodes ≥ 10 mm in longest dimension are considered malignant, regardless of nodal morphology. For pelvic nodes < 10 mm in longest dimension, if nodes are seen and are deemed to be morphologically benign in the opinion of the radiologist and surgeon, the patient is eligible. Patients with visible pelvic sidewall nodes are excluded
M0 stage based on no evidence of metastatic disease by CT imaging.
Mid to low-lying tumour eligible for local tumour excision in the opinion of the treating surgeon.
Age of at least 18 years.
Medically fit to undergo radical surgery as per treating surgeon's discretion
No contraindications to protocol chemotherapy.
Adequate normal organ and marrow function as defined below (must be done within 30 days prior to enrolment):
- ANC ≥ 1.5 x 109/L
- platelet count ≥100 x 109/L
- bilirubin < 1.5 ULN, excluding Gilbert's syndrome
- Calculated creatinine clearance of ≥ 50 ml/min.
- Clearance to be calculated using Cockcroft formula: Males: 1.23 x (140 - age) x weight (kg) - serum creatinine (μmol/l) ; Females: 1.05 x (140 - age) x weight (kg) - serum creatinine (μmol/l)
The patient must have an ECOG performance status of 0, 1.
Patient is able (i.e. sufficiently fluent) and willing to complete the quality of life and health utility questionnaires.
Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate.
Must be accessible for treatment and follow up. Patients registered on this trial must be treated with chemotherapy and followed at the enrolling centre.
Protocol treatment is to begin within 5 working days of patient enrollment.
Women/men of childbearing potential must have agreed to use a highly effective contraceptive method during and for 6 months after completion of chemotherapy.

Exclusion Criteria

Patient has pathologic high risk factors on either the initial biopsy specimen report or follow-up biopsy (if done): high histologic grade, mucinous histology, lymphatic or vascular invasion.
History of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≥ 5 years.
Synchronous cancer.
Prior treatment for rectal cancer.
Previous pelvic radiation for any reason.
Patients with known dihydropyrimidine dehydrogenase deficiency
Treatment with other investigational drugs or anti-cancer therapy within 28 days prior to enrolment.
Clinically significant (i.e. active) cardiovascular disease for example cerebro vascular accidents (< 6 months prior to enrolment), myocardial infarction (< 6 months prior to enrolment), unstable angina, New York Heart Association (NYHA) grade II or higher, congestive heart failure, serious cardiac arrhythmia requiring medication.
Any contra-indications to undergo MRI imaging.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
chemotherapy (FOLFOX or CAPOX) followed by tumour excision	Folfox Protocol	-
chemotherapy (FOLFOX or CAPOX) followed by tumour excision	Capox	-

Primary Outcome Measures

Name	Time	Method
Percentage of Organ Preservation	3 years	Defined as the percentage of patients with tumour downstaging to ypT0/T1good N0 and who avoid radical surgery.

Secondary Outcome Measures

Name	Time	Method
Percentage of Locoregional Relapses at 3 Years	3 years	Locoregional relapse is defined as reappearance of a tumour within the rectum or pelvis. The percentage of loco-reginal relapse at 3 years was estimated by Kaplan-Meier method for the survival function of the loco-regional relapse free survival, defined as the time from enrollment to the first date of definitive evidence (clinical, radiological or pathological) of locoregional relapses with patients who developed distant relapse only, died, loss to follow up, or were alive at clinical cut-off censored at respectively at last date of distant relapses, date of death, date of lost to follow-up, or last disease assessment date.
Percentage of Distant Relapse at 3 Years	3 years	Distant relapse is defined as appearance of rectal cancer disease at sites remote from the rectum. The percentage of distant relapse at 3 years was estimated also by Kaplan-Meier method for the survival function of the distant free survival, defined as the time from enrollment to the first date of definitive evidence (clinical, radiological or pathological) of distant relapses with patients who died, loss to follow up, or were alive at clinical cut-off censored at respectively: date of death, date of lost to follow-up, and last disease assessment date.
Percentage of Disease Free at 3 Years	3 years	Percentage of disease free at 3 years was estimated by Kaplan-Meier method for the survival function of Disease-Free Survival (DFS), which is defined as the interval from date of enrollment to the first date of the events defined below: * Locoregional relapse * Distant relapse * Non-protocol radiotherapy, chemotherapy, or biologic therapy without documentation of the site of failure * Death due to any other reason. Patients who were alive without locoregional or distant relapse or receiving non-protocol radiotherapy, chemotherapy, or biologic therapy without documentation of the site of failure at the clinical data cutoff date were censored at their last disease assessment date. 3 year disease free survival was estimated by Kaplan-Meier method.
Rate of Intraoperative Complications	1 day	Percentage of patients with at least one intraoperative injury

Trial Locations

Locations (11): UC Irvine Medical Center
🇺🇸
Orange, California, United States
Dana-Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
Virginia Mason Medical Center
🇺🇸
Seattle, Washington, United States
BCCA - Vancouver Cancer Centre
🇨🇦
Vancouver, British Columbia, Canada
St. Paul's Hospital
🇨🇦
Vancouver, British Columbia, Canada
CancerCare Manitoba
🇨🇦
Winnipeg, Manitoba, Canada
QEII Health Sciences Centre
🇨🇦
Halifax, Nova Scotia, Canada
Kingston Health Sciences Centre
🇨🇦
Kingston, Ontario, Canada
Ottawa Hospital Research Institute
🇨🇦
Ottawa, Ontario, Canada
Health Sciences North
🇨🇦
Sudbury, Ontario, Canada
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UC Irvine Medical Center
🇺🇸Orange, California, United States