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

Purpose

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.

Condition	Intervention	Phase
Operable T2-3N+M0 Rectal Cancer (Stage III)	Drug: FOLFOX Radiation: high dose rate endorectal brachytherapy	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	An Adaptative Randomized Phase II Study on the Timing of FOLFOX for Patients With Operable Stage III Rectal Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer

U.S. FDA Resources

Further study details as provided by Sir Mortimer B. Davis - Jewish General Hospital:

Primary Outcome Measures:

Compliance to chemotherapy - patients receiving at least 85% of planned full-dose of chemotherapy prescribed at each cycle for the 12 cycles [ Time Frame: 1 year post diagnosis ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Disease free survival rate (local recurrence and metastases) [ Time Frame: 5 years post surgery ] [ Designated as safety issue: Yes ]
Overall survival rate [ Time Frame: 5 years post surgery ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	180
Study Start Date:	November 2009
Estimated Study Completion Date:	December 2020
Estimated Primary Completion Date:	December 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: A - neoadjuvant chemotherapy 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	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.
Experimental: Arm B - adjuvant chemotherapy Patients in arm B will receive 12 cycles of FOLFOX after radiotherapy and surgery	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.

Arms

Assigned Interventions

Experimental: A - neoadjuvant chemotherapy

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

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.

Experimental: Arm B - adjuvant chemotherapy

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

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.

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01274962

Contacts

Contact: Chantal Cadieux, PhD	1-514-340-8222 ext 6199	ccadieux@jgh.mcgill.ca
Contact: Guerline Clerzius, PhD	1-514-340-8222 ext 8443	gclerzius@jgh.mcgill.ca

Locations

Canada, Quebec
Hôpital de Gatineau	Not yet recruiting
Gatineau, Quebec, Canada, J8T 8R2
Principal Investigator: Éric Bégin, MD
Hôpital Charles LeMoyne	Recruiting
Greenfield Park, Quebec, Canada, J4V 2H1
Principal Investigator: Nghia Nguyen, MD
Centre Hospitalier Pierre-Boucher	Recruiting
Longueuil, Quebec, Canada, J4M 2A5
Principal Investigator: Emery Ferland, MD
Principal Investigator: Te Vuong, MD
Sir Mortimer B. Davis - Jewish General Hospital	Recruiting
Montreal, Quebec, Canada, H3T 1E2
Principal Investigator: Te Vuong, MD
CHUM-Hôpital St-Luc	Not yet recruiting
Montréal, Quebec, Canada, H2X 3J4
Principal Investigator: Carole Richard, MD
CHUQ - Hôtel-Dieu de Québec	Active, not recruiting
Québec, Quebec, Canada, G1R 2J6
Hôpital Honoré-Mercier	Recruiting
Saint-Hyacinthe, Quebec, Canada, J2S 4Y8
Principal Investigator: Gilles Cuirot, MD

Sponsors and Collaborators

Sir Mortimer B. Davis - Jewish General Hospital

Sanofi

Investigators

Principal Investigator:

Te Vuong, MD

Sir Mortimer B. Davis - Jewish General Hospital

More Information

No publications provided

Responsible Party:	Dr. Te Vuong, Director Radiation Oncology Department, Sir Mortimer B. Davis - Jewish General Hospital
ClinicalTrials.gov Identifier:	NCT01274962 History of Changes
Other Study ID Numbers:	KIR 009
Study First Received:	January 11, 2011
Last Updated:	May 7, 2013
Health Authority:	Canada: Health Canada

Additional relevant MeSH terms:

Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site

Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases

ClinicalTrials.gov processed this record on May 19, 2013