Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Related Information
Registry Information

Alternate Title

Comparison of Adjuvant Chemotherapy Regimens in Treating Patients With Stage II or Stage III Rectal Cancer Who Are Receiving Radiation Therapy and Fluorouracil Before or After Surgery

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Closed 18 and over NCI ECOG-E3201 E3201, NCT00068692

Special Category: CTSU trial

Objectives

Primary

1. Compare the overall survival of patients with stage II or III rectal cancer receiving preoperative (group 1) or postoperative (group 2) radiotherapy and fluorouracil when additionally treated with adjuvant irinotecan, fluorouracil, and leucovorin calcium vs oxaliplatin, fluorouracil, and leucovorin calcium vs fluorouracil and leucovorin calcium.

Secondary

1. Determine sphincter preservation, tolerance of treatment, and patterns of failure in patients treated with these regimens.
2. Determine rectal function in patients treated with postoperative pelvic radiotherapy and chemotherapy.
3. Correlate tumor molecular prognostic markers (chromosome 18q allelic loss and microsatellite instability) with survival of patients treated with these regimens.
4. Determine physician preference in regard to the radiotherapy-chemotherapy sequence in these patients.
5. Correlate p53 gene mutation in tumor tissue with treatment efficacy in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed adenocarcinoma of the rectum
  • Stage II or III (T3-4, N0, M0 or any T, N1-3, M0)



• No distant metastases
  • No evidence of tumor outside of the pelvis, including liver metastases, peritoneal seeding, or metastatic inguinal lymphadenopathy



• Distal border of the tumor must be or have been at or below the peritoneal reflection, defined as within 12 cm of anal verge by protoscopic examination*

   [Note: *Tumor with a portion confirmed to be below the peritoneal reflection at the time of surgery is allowed regardless of the distance by endoscopy]




• Transmural penetration of tumor through the muscularis propria by CT scan, endorectal ultrasound, or MRI (group 1)



• Tumor must be defined prospectively by the surgeon as clinically resectable or not (group 1)



• Tumor may be clinically fixed or initially not completely resectable (clinical stage T4, N0-2, M0) based on the presence of at least 1 of the following criteria (group 1):
  • Tumor adherent to the pelvic sidewall or sacrum on rectal examination
  • Hydronephrosis on CT scan or intravenous pyelogram OR ureteric or bladder invasion by cystoscopy and cytology or biopsy OR invasion into prostate
  • Vaginal or uterine involvement

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy to the pelvis
• No concurrent intraoperative radiotherapy and/or brachytherapy

Surgery

• See Disease Characteristics

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,500/mm³
• Platelet count at least 100,000/mm³

Hepatic

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST no greater than 3 times ULN

Renal

• Creatinine no greater than 1.5 times ULN

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other prior or concurrent malignancy except nonmelanoma skin cancer, carcinoma in situ of the cervix, or other treated non-pelvic cancer from which the patient has been disease-free for more than 5 years
• No active inflammatory bowel disease
• No other serious medical illness that would preclude study treatment

Expected Enrollment

A total of 3,000 patients (1,000 per treatment arm) will be accrued for this study over 5 years.

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 1 (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 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.

Benson AB, Catalano P, Meropol NJ, et al.: ECOG E3201: intergroup randomized phase III study of postoperative irinotecan, 5- fluorouracil (FU), leucovorin (LV) (FOLFIRI) vs oxaliplatin, FU/LV (FOLFOX) vs FU/LV for patients (pts) with stage II/ III rectal cancer receiving either pre or postoperative radiation (RT)/ FU. [Abstract] J Clin Oncol 24 (Suppl 18): A-3526, 152s, 2006.

Trial Contact Information

Trial Lead Organizations

Eastern Cooperative Oncology Group

Al Benson, MD, FACP, Protocol chair		Ph: 312-695-6180
Bruce Giantonio, MD, Protocol co-chair(Contact information may not be current)		Ph: 215-662-8624
Neal Meropol, MD, Protocol co-chair		Ph: 215-728-2450; 888-369-2427

Related Information

PDQ® clinical trial NSABP-R-04

Registry Information
Official Title		Intergroup Randomized Phase III Study Of Postoperative Irinotecan, 5-Fluorouracil And Leucovorin Vs Oxaliplatin, 5-Flourouracil 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-Flourouracil
Trial Start Date		2003-10-15
Registered in ClinicalTrials.gov		NCT00068692
Date Submitted to PDQ		2003-08-04
Information Last Verified		2005-11-01
NCI Grant/Contract Number		CA21115

Back to Top