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
Principal Investigator: Peter Kozuch, M.D.
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.
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)
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Pathologic Complete Response
Peter Kozuch, MD
Beth Israel Medical Center
United States: Institutional Review Board
|Beth Israel Medical Center||New York, New York 10003|
|St. Luke's Roosevelt Hospital Center||New York, New York 10019|