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

Sir Mortimer B. Davis - Jewish General Hospital

Status and phase: Completed; Phase 2

Conditions: Operable T2-3N+M0 Rectal Cancer (Stage III)

Treatments: Radiation: high dose rate endorectal brachytherapy; Drug: FOLFOX

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01274962

KIR 009

Details and patient eligibility

About

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.

Full 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.

Enrollment: 180 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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180 participants in 2 patient groups

A - neoadjuvant chemotherapy

Experimental group

Description:

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

Treatment:

Drug: FOLFOX

Radiation: high dose rate endorectal brachytherapy

Arm B - adjuvant chemotherapy

Experimental group

Description:

Patients in arm B will receive 12 cycles of FOLFOX after radiotherapy and surgery

Treatment:

Drug: FOLFOX

Radiation: high dose rate endorectal brachytherapy