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

Operable T2-3N+M0 Rectal Cancer (Stage III) Clinical Trial

Official title:

An Adaptative Randomized Phase II Study on the Timing of FOLFOX for Patients With Operable Stage III Rectal Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01274962
• Other study ID #: KIR 009
• Status: Completed
• Phase: Phase 2
• Start date: November 2009
• Est. completion date: December 2022

Study information

• Verified date: May 2023
• Source: Sir Mortimer B. Davis - Jewish General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 180
• Est. completion date: December 2022
• Est. primary completion date: December 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Operable T2-3N+M0 Rectal Cancer (Stage III)
• Rectal Neoplasms

Intervention

Drug:
• FOLFOX
Oxaliplatin* 85 mg/m2 IV in 500 mL of D5W over 120 minutes Folinic Acid (Leucovorin)* 400 mg/m2 IV in 250 ml D5W over 120 minutes 5-Fluorouracil (5-FU) 400 mg/m2 IV bolus, after Folinic Acid 5-Fluorouracil** 2400 mg/m2 IV over 46 h in D5W to a total volume of 92 mL by continuous infusion at 2 mL/hour. Repeat every 14 days for 6 cycles in the arm A and to be completed with 6 cycles after surgery and 12 cycles in arm B. If necessary the schedule may be modified +/- 3 days.

Radiation:
• high dose rate endorectal brachytherapy
High dose rate endorectal brachytherapy, consisting in a total dose of 26 Gy in 4 daily fractions of 6.5 Gy.

Locations

Country	Name	City	State
Canada	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	CHUQ - Hôtel-Dieu de Québec	Québec
Canada	Hôpital Honoré-Mercier	Saint-Hyacinthe	Quebec
Canada	Hôpital du Suroît	Salaberry-De-Valleyfield	Quebec

Sponsors (2)

Lead Sponsor	Collaborator
Sir Mortimer B. Davis - Jewish General Hospital	Sanofi

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Disease free survival rate (local recurrence and metastases)		5 years post surgery
Secondary	Overall survival rate		5 years post surgery