A Study on the Timing of FOLFOX for Patients With Operable, Node Positive Rectal Cancer

Phase 2

Completed

• Conditions: Operable T2-3N+M0 Rectal Cancer (Stage III)
• Interventions: Drug: FOLFOX; Radiation: high dose rate endorectal brachytherapy

• Registration Number: NCT01274962
• Lead Sponsor: Sir Mortimer B. Davis - Jewish General Hospital

Brief Summary

This study is proposed to evaluate whether giving part of the chemotherapy prior to radiotherapy and surgery (as opposed to standard of care, which involves giving all the chemotherapy after radiotherapy and surgery) for patients with node positive operable rectal cancer will result in higher patient compliance to chemotherapy.

Detailed Description

In recent randomized studies with preoperative combined chemotherapy and external beam radiation (EBRT/CT) with total mesorectal excision (TME surgery), the compliance to adjuvant chemotherapy ranged from 42.9% to 70%. This low compliance rate could influence the efficacy of chemotherapy. This is quite unique to patients with rectal cancer, since compliance is not a major issue in patients with colon cancer, belonging to the same age group. Therefore, it is reasonable to postulate that this difference might due to the additive toxicity burden of neoadjuvant EBRT/CT and TME.

In this randomized phase II study, compliance to chemotherapy will be compared in the two groups: In the first group, patients will receive half of their chemotherapy regimen in neoadjuvant and half in adjuvant; and, in the second group, patients will be receiving all their chemotherapy in adjuvant. Furthermore, brachytherapy will be used to deliver radiotherapy.

Study Timeline

• Study Start: 2009-11
• Study First Submitted: 2011-01-11
• Study First Submitted QC: 2011-01-11
• Study First Posted: 2011-01-12
• Primary Completion: 2022-12
• Study Completion: 2022-12
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-25
• Last Update Posted: 2024-06-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 180

Inclusion Criteria

1. Pathology: Adenocarcinoma of the rectum.
2. T2 (CRM+) or T3 tumour at ≤ 10 cm from the A-V margin (as per MRI criteria)
3. Evidence of perirectal nodes on MRI or EUS (N1 or N2), any CRM+ and N0 tumor, or any EMVI+ tumor
4. Tumors with an adequate lumen to allow the positioning of the Oncosmart intracavitary mould applicator (e.g. non obstructive tumor).
5. Tumour of less than 3.5 cm thickness documented at the CT Simulator.
6. Patient should be a suitable candidate for surgery and chemotherapy.
7. WHO performance status 0-2
8. Age > 18 years.
9. Written informed consent.
10. Adequate birth control measures in women with childbearing potential.

Exclusion Criteria

1. Patients with positive extramesorectal or pelvic nodes (e.g. iliac, lateral).
2. Evidence of distant metastases (M1).
3. Previous pelvic radiation.
4. Other cancers except for basal cell carcinoma of the skin or CIS of the cervix.
5. Presence of multiples small bowel loops trapped within the immediate tumor bed (post hysterectomy or prostatectomy).
6. Extension of malignant disease to the anal canal
7. Patients with severe co-morbid conditions (recent MI, infections, AIDS, etc)
8. Pregnancy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A - neoadjuvant chemotherapy	FOLFOX	Patients in arm A will receive 6 cycles of FOLFOX chemotherapy prior to radiotherapy and surgery as well as 6 cycles of chemotherapy in adjuvant
A - neoadjuvant chemotherapy	high dose rate endorectal brachytherapy	Patients in arm A will receive 6 cycles of FOLFOX chemotherapy prior to radiotherapy and surgery as well as 6 cycles of chemotherapy in adjuvant
Arm B - adjuvant chemotherapy	FOLFOX	Patients in arm B will receive 12 cycles of FOLFOX after radiotherapy and surgery
Arm B - adjuvant chemotherapy	high dose rate endorectal brachytherapy	Patients in arm B will receive 12 cycles of FOLFOX after radiotherapy and surgery

Primary Outcome Measures

Name	Time	Method
Compliance to chemotherapy - patients receiving at least 85% of planned full-dose of chemotherapy prescribed at each cycle for the 12 cycles	1 year post diagnosis

Secondary Outcome Measures

Name	Time	Method
Disease free survival rate (local recurrence and metastases)	5 years post surgery
Overall survival rate	5 years post surgery

Trial Locations

Locations (8)

Hôpital de Gatineau; 🇨🇦 Gatineau, Quebec, Canada

Hôpital Charles LeMoyne; 🇨🇦 Greenfield Park, Quebec, Canada

Centre Hospitalier Pierre-Boucher; 🇨🇦 Longueuil, Quebec, Canada

Sir Mortimer B. Davis - Jewish General Hospital; 🇨🇦 Montreal, Quebec, Canada

CHUM-Hôpital St-Luc; 🇨🇦 Montréal, Quebec, Canada

Hôpital Honoré-Mercier; 🇨🇦 Saint-Hyacinthe, Quebec, Canada

Hôpital du Suroît; 🇨🇦 Salaberry-De-Valleyfield, Quebec, Canada

CHUQ - Hôtel-Dieu de Québec; 🇨🇦 Québec, Canada