|Fluorouracil and Leucovorin With or Without Irinotecan in Treating Patients Following Surgery for Stage III Colorectal Cancer|
|Multicenter Phase III Open Label Randomized Trial Comparing CPT-11 In Combination With A 5-FU/FA Infusional Regimen To The Same 5-FU/FA Infusional Regimen Alone As Adjuvant Treatment Of Stage III Colon Cancer|
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving them after surgery may kill more tumor cells.
PURPOSE: Randomized phase III trial to compare the effectiveness of fluorouracil and leucovorin with or without irinotecan in treating patients who have undergone surgery for stage III colorectal cancer.
- Compare the disease-free survival at 3 years of patients with resected stage III colorectal cancer treated with adjuvant fluorouracil and leucovorin calcium with or without irinotecan.
- Compare the disease-free and overall survival at 5 years of patients treated with these regimens.
- Compare the safety profiles of these treatment regimens in these patients.
- Compare the quality-adjusted survival of patients treated with these regimens.
- Correlate the expression of putative prognostic markers (thymidylate synthase, telomerase, topoisomerase) with disease-free and overall survival of patients treated with these regimens.
OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to participating center. Patients are randomized to 1 of 2 treatment arms.
- Patients receive irinotecan IV over 30-90 minutes, leucovorin calcium IV over 2 hours, and fluorouracil IV over 24 hours weekly for 6 weeks. Courses repeat every 7 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
- As an alternative schedule, patients may receive irinotecan IV over 30-90 minutes and day 1 and leucovorin calcium IV over 2 hours and fluorouracil IV over 22 hours on days 1 and 2 every 2 weeks for 6 weeks. Treatment repeats every 6 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
- Patients receive leucovorin calcium and fluorouracil as in arm I. Quality of life may be assessed at baseline; prior to courses 2, 3, and 4; and at 1, 3, and 6 months.
Patients are followed every 3 months for 3 years and then every 6 months for 2 years.
PROJECTED ACCRUAL: Approximately 1800 patients (900 per arm) will be accrued for this study within 24 months.
Masking: None (Open Label)
Primary Purpose: Treatment
- Drug: FOLFIRI regimen
- Drug: fluorouracil
- Drug: irinotecan hydrochloride
- Drug: leucovorin calcium
- Punt CJ, Buyse M, Köhne CH, Hohenberger P, Labianca R, Schmoll HJ, Påhlman L, Sobrero A, Douillard JY. Endpoints in adjuvant treatment trials: a systematic review of the literature in colon cancer and proposed definitions for future trials. J Natl Cancer Inst. 2007 Jul 4;99(13):998-1003. Epub 2007 Jun 27. Review.
- Delorenzi M, Budinska E, Popovici V, et al.: Molecular classes in CRC: characterization of MSI by expression profiling in the translational study of the PETACC 3-EORTC 40993- SAKK 60-00 trial. [Abstract] J Clin Oncol 28 (Suppl 15): A-3597, 2010.
- Roth AD, Tejpar S, Delorenzi M, Yan P, Fiocca R, Klingbiel D, Dietrich D, Biesmans B, Bodoky G, Barone C, Aranda E, Nordlinger B, Cisar L, Labianca R, Cunningham D, Van Cutsem E, Bosman F. Prognostic role of KRAS and BRAF in stage II and III resected colon cancer: results of the translational study on the PETACC-3, EORTC 40993, SAKK 60-00 trial. J Clin Oncol. 2010 Jan 20;28(3):466-74. doi: 10.1200/JCO.2009.23.3452. Epub 2009 Dec 14.
- Bosman FT, Yan P, Tejpar S, Fiocca R, Van Cutsem E, Kennedy RD, Dietrich D, Roth A. Tissue biomarker development in a multicentre trial context: a feasibility study on the PETACC3 stage II and III colon cancer adjuvant treatment trial. Clin Cancer Res. 2009 Sep 1;15(17):5528-33. doi: 10.1158/1078-0432.CCR-09-0741. Epub 2009 Aug 18.
- Tejpar S, Bosman F, Delorenzi M, et al.: Microsatellite instability (MSI) in stage II and III colon cancer treated with 5FU-LV or 5FU-LV and irinotecan (PETACC 3-EORTC 40993-SAKK 60/00 trial). [Abstract] J Clin Oncol 27 (Suppl 15): A-4001, 2009.
- Van Cutsem E, Labianca R, Bodoky G, Barone C, Aranda E, Nordlinger B, Topham C, Tabernero J, André T, Sobrero AF, Mini E, Greil R, Di Costanzo F, Collette L, Cisar L, Zhang X, Khayat D, Bokemeyer C, Roth AD, Cunningham D. Randomized phase III trial comparing biweekly infusional fluorouracil/leucovorin alone or with irinotecan in the adjuvant treatment of stage III colon cancer: PETACC-3. J Clin Oncol. 2009 Jul 1;27(19):3117-25. doi: 10.1200/JCO.2008.21.6663. Epub 2009 May 18.
- Roth AD, Yan P, Dietrich D, et al.: Does UGT1A1*28 homozygosity predict for severe toxicity in patients treated with 5-fluorouracil (5-FU)-irinotecan (IRI)? Results of the PETACC 3-EORTC 40993-SAKK 60/00 trial comparing IRI/5-FU/folinic acid (FA) to 5-FU/FA in stage II-III colon cancer. [Abstract] American Society of Clinical Oncology 2008 Gastrointestinal Cancers Symposium, 25-27 January 2008, Orlando, FL. A-277, 2008.
- Roth AD, Yan P, Dietrich D, et al.: Is UGT1A1*28 homozygosity the strongest predictor for severe hematotoxicity in patients treated with 5-fluorouracil (5-FU)-irinotecan (IRI)? Results of the PETACC 3 - EORTC 40993 -SAKK 60/00 trial comparing IRI/5-FU/folinic acid (FA) to 5-FU/FA in stage II- III colon cancer (COC) patients. [Abstract] J Clin Oncol 26 (Suppl 15): A-4036, 2008.
- van Cutsem E, Labianca R, Hossfeld D, et al.: Randomized phase III trial comparing infused irinotecan / 5-fluorouracil (5-FU)/folinic acid (IF) versus 5-FU/FA (F) in stage III colon cancer patients (pts). (PETACC 3). [Abstract] J Clin Oncol 23 (Suppl 16): A-LBA8, 3s, 2005.
- Klingbiel D, Saridaki Z, Roth AD, Bosman FT, Delorenzi M, Tejpar S. Prognosis of stage II and III colon cancer treated with adjuvant 5-fluorouracil or FOLFIRI in relation to microsatellite status: results of the PETACC-3 trial. Ann Oncol. 2015 Jan;26(1):126-32. doi: 10.1093/annonc/mdu499. Epub 2014 Oct 30.
|September 2004 (Final data collection date for primary outcome measure)|
- Absolute neutrophil count at least 2,000/mm^3
- Platelet count at least 150,000/mm^3
- Hemoglobin at least 10 g/dL
- Bilirubin no greater than upper limit of normal (ULN)
- AST and ALT no greater than 2.5 times ULN
- Alkaline phosphatase no greater than 2.5 times ULN
- Creatinine no greater than 1.5 mg/dL OR
- Creatinine clearance at least 60 mL/min
- No myocardial infarction with the past year
- No uncontrolled hypertension
- No high-risk uncontrolled arrhythmia
- No unstable angina pectoris
- HIV negative
- No chronic diarrhea
- No current chronic inflammation or subobstruction of bowel after surgery
- No active uncontrolled infection
- No other prior or concurrent malignancy except curatively treated nonmelanoma skin cancer or carcinoma in situ of the cervix
- No psychological, social, familial, or geographical condition that would preclude follow-up
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 6 months after study participation
PRIOR CONCURRENT THERAPY:
- No prior antineoplastic chemotherapy
- See Disease Characteristics
- See Disease Characteristics
- No prior celioscopic resection of primary tumor
- At least 30 days since prior participation in another clinical trial with any investigational drug
- No other concurrent experimental drugs
- No other concurrent anticancer therapy
|Sexes Eligible for Study:||All|
|18 Years to 75 Years (Adult, Older Adult)|
|Contact information is only displayed when the study is recruiting subjects|
|Austria, Belgium, Egypt, France, Germany, Italy, Portugal, Spain, Switzerland, United Kingdom|
|Study Chair:||Eric Van Cutsem, MD, PhD||University Hospital, Gasthuisberg|