Recurrent Rectal Carcinoma Clinical Trial
Official title:
Intergroup Randomized Phase III Study of Postoperative Irinotecan, 5-Fluorouracil and Leucovorin vs. Oxaliplatin, 5-Fluorouracil and Leucovorin vs. 5-Fluorouracil and Leucovorin for Patients With Stage II or III Rectal Cancer Receiving Either Preoperative Radiation and 5-Fluorouracil or Postoperative Radiation and 5-Fluorouracil
This randomized phase III trial is comparing the effectiveness of three adjuvant combination chemotherapy regimens in treating patients who are receiving radiation therapy and fluorouracil either before or after surgery for stage II or stage III rectal cancer. Drugs used in chemotherapy, such as irinotecan, fluorouracil, leucovorin, and oxaliplatin, use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known which adjuvant combination chemotherapy regimen is more effective in treating patients who are receiving radiation therapy and fluorouracil either before or after surgery for rectal cancer.
PRIMARY OBJECTIVES:
I. To compare the overall survival of patients treated with irinotecan, 5-FU and leucovorin
versus those treated with oxaliplatin, leucovorin and 5-FU versus those treated with
leucovorin and 5-FU for patients with stage II and III rectal cancer.
SECONDARY OBJECTIVES:
I. To determine sphincter preservation, tolerance of treatment and patterns of failure.
II. To describe patterns of failures
OTHER PRE-SPECIFIED OBJECTIVES:
I.To prospectively assess rectal function using the Patient Bowel Function/Uniscale
questionnaire and the FACT Diarrhea Subscale in patients treated with an adjuvant program of
pelvic radiation therapy and chemotherapy.
II. To correlate expression of key targets for 5-FU, leucovorin, oxaliplatin and irinotecan
from tumor tissue biopsies with treatment efficacy III. To correlate tumor molecular
prognostic markers with survival. IV. To determine physician preference in regard to the
radiation-chemotherapy sequence in the Intergroup.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to ECOG
performance status (0 vs 1), chemotherapy/radiotherapy sequence (preoperative vs
postoperative), and risk group (high risk [T3, N+, M0 or T4, any N, M0] vs low risk [T1-2,
N+, M0 or T3, N0, M0]). Patients are treated in 1 of 2 groups according to physician
preference and then randomized to 1 of 3 treatment arms.
GROUP I (preoperative chemoradiotherapy and additional adjuvant chemotherapy): Preoperative
chemoradiotherapy: Patients receive 1 of 3 treatment regimens, determined by the treating
physician.
REGIMEN A (radiotherapy and fluorouracil): Patients undergo external beam radiotherapy once
daily 5 days a week for 5 1/2 weeks (total of 28 fractions). Patients also receive concurrent
fluorouracil intravenously (IV) continuously 7 days a week for 5 1/2 weeks.
REGIMEN B (radiotherapy, fluorouracil, and leucovorin calcium): Patients undergo external
beam radiotherapy as in regimen A. Patients also receive concurrent fluorouracil IV and
leucovorin calcium IV continuously for 4 days on weeks 1 and 5.
REGIMEN C (radiotherapy and capecitabine)*: Patients undergo external beam radiotherapy as in
regimen A. Patients also receive concurrent oral capecitabine twice daily for 5 1/2 weeks.
NOTE: *Regimen C is allowed only for patients enrolled on protocol NSABP-R-04.
Surgery: Within 21-56 days after the completion of chemoradiotherapy, patients undergo
surgical resection.
Additional adjuvant chemotherapy: Within 21-56 days after complete surgical resection,
patients are randomized to 1 of 3 treatment arms.
ARM I: Patients receive irinotecan IV over 90 minutes and leucovorin calcium IV over 2 hours
followed immediately by fluorourcil IV bolus on day 1. Patients also receive fluorouracil IV
continuously over 46 hours beginning on day 1. Treatment repeats every 2 weeks for 8 courses.
ARM II: Patients receive oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours
followed immediately by fluorourcil IV bolus on day 1. Patients also receive fluorouracil IV
continuously over 46 hours beginning on day 1. Treatment repeats every 2 weeks for 8 courses.
ARM III: Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV over 1 hour
on days 1, 8, 15, 22, 29, and 36. Treatment repeats every 8 weeks for 3 courses.
In all arms, treatment continues in the absence of disease progression or unacceptable
toxicity.
GROUP 2 (postoperative chemoradiotherapy and additional adjuvant chemotherapy): Within 21-56
days after complete surgical resection, patients are randomized to 1 of 3 treatment arms.
ARM I: Patients receive irinotecan, leucovorin calcium, and fluorouracil as in group 1, arm I
for 4 courses.
ARM II: Patients receive oxaliplatin, leucovorin calcium, and fluorouracil as in group 1, arm
II for 4 courses.
ARM III: Patients receive leucovorin calcium and fluorouracil as in group 1, arm III for 1
course.
Within 4 weeks after the completion of chemotherapy, all patients undergo concurrent pelvic
chemoradiotherapy as described in group 1 preoperative chemoradiotherapy Regimen A, B, or C,
followed 4-6 weeks later by 4 additional courses of adjuvant chemotherapy for arms I and II
and 2 additional courses of adjuvant chemotherapy for arm III.
Treatment continues in the absence of disease progression or unacceptable toxicity.
Patients are followed every 3 months for 3 years, every 6 months for 2 years, and then
annually for 5 years.
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