A Study on the Timing of FOLFOX for Patients With Operable, Node Positive Rectal Cancer
Primary Purpose
Operable T2-3N+M0 Rectal Cancer (Stage III)
Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
FOLFOX
high dose rate endorectal brachytherapy
Sponsored by
About this trial
This is an interventional treatment trial for Operable T2-3N+M0 Rectal Cancer (Stage III)
Eligibility 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
Sites / Locations
- Hôpital de Gatineau
- Hôpital Charles LeMoyne
- Centre Hospitalier Pierre-Boucher
- Sir Mortimer B. Davis - Jewish General Hospital
- CHUM-Hôpital St-Luc
- Hôpital Honoré-Mercier
- Hôpital du Suroît
- CHUQ - Hôtel-Dieu de Québec
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
A - neoadjuvant chemotherapy
Arm B - adjuvant chemotherapy
Arm 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
Patients in arm B will receive 12 cycles of FOLFOX after radiotherapy and surgery
Outcomes
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
Secondary Outcome Measures
Disease free survival rate (local recurrence and metastases)
Overall survival rate
Full Information
NCT ID
NCT01274962
First Posted
January 11, 2011
Last Updated
May 23, 2023
Sponsor
Sir Mortimer B. Davis - Jewish General Hospital
Collaborators
Sanofi
1. Study Identification
Unique Protocol Identification Number
NCT01274962
Brief Title
A Study on the Timing of FOLFOX for Patients With Operable, Node Positive Rectal Cancer
Official Title
An Adaptative Randomized Phase II Study on the Timing of FOLFOX for Patients With Operable Stage III Rectal Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
November 2009 (Actual)
Primary Completion Date
December 2022 (Actual)
Study Completion Date
December 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sir Mortimer B. Davis - Jewish General Hospital
Collaborators
Sanofi
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Operable T2-3N+M0 Rectal Cancer (Stage III)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
180 (Actual)
8. Arms, Groups, and Interventions
Arm Title
A - neoadjuvant chemotherapy
Arm Type
Experimental
Arm 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
Arm Title
Arm B - adjuvant chemotherapy
Arm Type
Experimental
Arm Description
Patients in arm B will receive 12 cycles of FOLFOX after radiotherapy and surgery
Intervention Type
Drug
Intervention Name(s)
FOLFOX
Intervention Description
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.
Intervention Type
Radiation
Intervention Name(s)
high dose rate endorectal brachytherapy
Intervention Description
High dose rate endorectal brachytherapy, consisting in a total dose of 26 Gy in 4 daily fractions of 6.5 Gy.
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
Disease free survival rate (local recurrence and metastases)
Time Frame
5 years post surgery
Title
Overall survival rate
Time Frame
5 years post surgery
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Te Vuong, MD
Organizational Affiliation
Sir Mortimer B. Davis - Jewish General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hôpital de Gatineau
City
Gatineau
State/Province
Quebec
ZIP/Postal Code
J8T 8R2
Country
Canada
Facility Name
Hôpital Charles LeMoyne
City
Greenfield Park
State/Province
Quebec
ZIP/Postal Code
J4V 2H1
Country
Canada
Facility Name
Centre Hospitalier Pierre-Boucher
City
Longueuil
State/Province
Quebec
ZIP/Postal Code
J4M 2A5
Country
Canada
Facility Name
Sir Mortimer B. Davis - Jewish General Hospital
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1E2
Country
Canada
Facility Name
CHUM-Hôpital St-Luc
City
Montréal
State/Province
Quebec
ZIP/Postal Code
H2X 3J4
Country
Canada
Facility Name
Hôpital Honoré-Mercier
City
Saint-Hyacinthe
State/Province
Quebec
ZIP/Postal Code
J2S 4Y8
Country
Canada
Facility Name
Hôpital du Suroît
City
Salaberry-De-Valleyfield
State/Province
Quebec
ZIP/Postal Code
J6T 6C1
Country
Canada
Facility Name
CHUQ - Hôtel-Dieu de Québec
City
Québec
ZIP/Postal Code
G1R 2J6
Country
Canada
12. IPD Sharing Statement
Learn more about this trial
A Study on the Timing of FOLFOX for Patients With Operable, Node Positive Rectal Cancer
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