Clinical trial NCT00832299
Conditions: Rectal Neoplasms
Sponsor: Beth Israel Medical Center
Start date: 2009-01-01; Completion date: 2011-08-01
Enrollment: 2 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
A Phase II open- labeled, prospective study to determine the efficacy of pre-operative chemotherapy with six cycles of modified FOLFOX 6 followed by total mesorectal excision (TME) followed by an additional six cycles of FOLFOX 6.

The objectives of this study are the following:

1. The primary endpoint of this trial is pathologic complete response (response rate).
2. Secondary endpoints will include observation of overall pathologic response rate, correlation of pathologic staging with pre-operative ultrasound and pelvic MRI staging, as well as observation of toxic side effects, patterns of disease relapse, disease-free survival outcomes and overall survival outcomes.

Detailed description:
Principal Investigator: Peter Kozuch, M.D.

Sites: BIMC/SLRHC

Introduction

A Phase II open- labeled, prospective study to determine the efficacy of pre-operative chemotherapy with six cycles of modified FOLFOX 6 followed by total mesorectal excision (TME) followed by an additional six cycles of FOLFOX 6.

The objectives of this study are the following:

1. The primary endpoint of this trial is pathologic complete response (response rate).
2. Secondary endpoints will include observation of overall pathologic response rate, correlation of pathologic staging with pre-operative ultrasound and pelvic MRI staging, as well as observation of toxic side effects, patterns of disease relapse, disease-free survival outcomes and overall survival outcomes.

Background Locally advanced rectal carcinoma continues to be a major oncologic problem in the United States. Several landmark studies have led to the current standard approach to the care of patients with stage II and III rectal cancer. In 1990 adjuvant 5- fluorouracil based chemoradiation became the accepted standard of care on the basis of two randomized trials. During the following two decades significant modifications were made to both the administration of chemoradiation therapy and surgery. First, continuous infusion 5-fluorouracil daily concurrent with radiation to was shown to be superior to bolus 5-fluorouracil for 3 consecutive days during weeks 1 and 5 of radiation. The overall rate of tumor relapse fell from 47% to 37%, and distant metastasis rate fell from 40% to 31%. Notably, local tumor recurrence was not significantly different between the two chemotherapy schedules. The improvement in relapse rate translated into a 4 year survival benefit, 70% versus 60%, favoring the protracted venous infusion of 5-fluorouracil (5-FU).

What is not known, however, is the relative contribution of radiation therapy to survival outcomes in the setting of chemotherapy programs for rectal cancer. Optimization of systemic therapy appears to have the most significant impact on survival outcomes. Firstly, patients may begin full systemic therapy with the regimen that has currently been identified as the most effective adjuvant treatment of stage III colon cancer. This relatively prompt initiation of 'full systemic dose' chemotherapy is in stark contrast to the typical paradigm of a 3-4 week interval between initial consultation and initiation of chemoradiation. Another theoretical advantage of this proposed trial lies in the fact that full systemic therapy is relatively uninterrupted. Therefore, the anticipated 6-8 week perioperative treatment free interval anticipated in this schema compares favorably with the typical 10-12 week perioperative treatment free interval with current standard of care neoadjuvant chemoradiation. Another important consideration favoring this chemotherapy is substantially less travel time/treatment time for patients and favorable toxicity profile given the elimination of daily neoadjuvant radiation.

Treatment Plan

Patients will be given:

* Modified FOLFOX6 will be given neoadjuvantly prior to resection for 3 months (6 cycles)
* Modified FOLFOX6 will be given adjuvantly within 6 weeks following resection for 3 months (6 cycles)

Arms: arm 1: None
Interventions: intervention 1: FOLFOX intervention 2: total mesorectal excision (TME)
Intervention descriptions: intervention 1: 6 cycles of neo-adjuvant mFOLFOX6 intervention 2: TME will be done 4-6 weeks after 6 cycles of neo-adjuvant FOLFOX.

Protocol documents: