Sunitinib Malate and Combination Chemotherapy as Front-Line Therapy in Treating Patients With Metastatic Rectal Cancer That Cannot Be Removed by Surgery
RATIONALE: Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as irinotecan hydrochloride, leucovorin calcium, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) together with sunitinib malate may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving sunitinib malate together with combination chemotherapy works as front-line therapy in treating patients with metastatic rectal cancer that cannot be removed by surgery.
Drug: FOLFIRI regimen
Drug: irinotecan hydrochloride
Drug: leucovorin calcium
Drug: sunitinib malate
Other: laboratory biomarker analysis
Other: pharmacogenomic studies
Other: pharmacological study
|Study Design:||Allocation: Non-Randomized
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Front-line Combination Therapy of Sunitinib Malate Plus Chemotherapy With Leucovorin/5-Fluorouracil and Irinotecan (FOLFIRI) for Rectal Cancer Patients With Synchronous Non-Resectable Metastases: A Phase II Non Controlled Study. (SUREMETS)|
- Response rate at 3 months as assessed by RECIST criteria [ Designated as safety issue: No ]
- Rate of complete response after resection [ Designated as safety issue: No ]
- Rate of R0 resection of metastases [ Designated as safety issue: No ]
- Rate of local failure [ Designated as safety issue: No ]
- Rate of local complications [ Designated as safety issue: No ]
- Metastatic progression-free survival [ Designated as safety issue: No ]
- Local progression-free survival [ Designated as safety issue: No ]
- Disease-free survival [ Designated as safety issue: No ]
- Symptom-free survival [ Designated as safety issue: No ]
- Overall survival [ Designated as safety issue: No ]
- Quality of life, specifically fatigue and global health score (EORTC QLQ-C30) [ Designated as safety issue: No ]
- Time to deterioration of the final score for overall health and fatigue [ Designated as safety issue: No ]
- Tolerance and incidence of side effects as assessed by NCI CTCAE v2 [ Designated as safety issue: Yes ]
- Translational research including pharmacodynamic studies of plasma and rectal tumor biopsies and histological and molecular studies [ Designated as safety issue: No ]
|Study Start Date:||April 2009|
- Evaluation of the efficacy of front-line treatment with sunitinib malate and FOLFIRI chemotherapy at 3 months in patients with rectal cancer and synchronous metastases deemed unresectable in a multidisciplinary consultation.
- Evaluate the rate of resection of secondary metastases and rectal cancer, rate of R0 resection of metastases and rectal cancer, and the rate of complete response after resection.
- Evaluate the rate of local failure (progression of rectal cancer).
- Evaluate the rate of local complications.
- Evaluate disease-free survival.
- Evaluate progression-free survival, metastatic progression-free survival, and local progression-free survival.
- Evaluate symptom-free survival.
- Evaluate overall survival.
- Evaluate quality of life, specifically fatigue and global health score (EORTC QLQ-C30).
- Evaluate the tolerance to treatment.
- Conduct translational research, in particular, pharmacokinetic studies of plasma and rectal tumor biopsies, and histological and molecular studies.
OUTLINE: Patients receive simplified FOLFIRI chemotherapy comprising irinotecan hydrochloride IV over 90 minutes, leucovorin calcium IV over 2 hours, and fluorouracil IV over 46 hours on days 1, 15, and 29. Patients also receive oral sunitinib malate once daily on days 1-28. Treatment repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.
Patients may undergo surgical resection and/or local radiotherapy if the tumor regresses. After resection or radiotherapy, patients may undergo up to 4 more courses of study treatment.
Biopsies of the tumor and healthy mucosa are collected for translational research at baseline. Blood samples are collected for pharmacodynamic and pharmacogenetic studies at baseline and at week 6. Patients also complete a quality-of-life questionnaire (EORTC QLQ-C30) at baseline and periodically thereafter.
After completion of study therapy, patients are followed up every 12 weeks.
|Hopital Ambroise Pare|
|Boulogne Billancourt, France, 92100|
|Principal Investigator:||Philippe Rougier, MD||Hopital Ambroise Pare|