Sunitinib Malate and Combination Chemotherapy as Front-Line Therapy in Treating Patients With Metastatic Rectal Cancer That Cannot Be Removed by Surgery

Sponsor

Federation Francophone de Cancerologie Digestive (Other)

Overall Status

Withdrawn

CT.gov ID

NCT00936832

Collaborator

(none)

Enrollment

Location

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer Metastatic Cancer	Drug: FOLFIRI regimen Drug: fluorouracil Drug: irinotecan hydrochloride Drug: leucovorin calcium Drug: sunitinib malate Other: laboratory biomarker analysis Other: pharmacogenomic studies Other: pharmacological study	Phase 2

Detailed Description

OBJECTIVES:

Primary

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.

Secondary

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Non-Randomized

Masking:

None (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)

Study Start Date :

Apr 1, 2009

Outcome Measures

Primary Outcome Measures

Response rate at 3 months as assessed by RECIST criteria []

Secondary Outcome Measures

Rate of complete response after resection []
Rate of R0 resection of metastases []
Rate of local failure []
Rate of local complications []
Metastatic progression-free survival []
Local progression-free survival []
Disease-free survival []
Symptom-free survival []
Overall survival []
Quality of life, specifically fatigue and global health score (EORTC QLQ-C30) []
Time to deterioration of the final score for overall health and fatigue []
Tolerance and incidence of side effects as assessed by NCI CTCAE v2 []
Translational research including pharmacodynamic studies of plasma and rectal tumor biopsies and histological and molecular studies []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed adenocarcinoma of the rectum
Lower pole of the tumor < 12 cm from the anal margin
Synchronous metastases of the liver and/or lung
Unresectable or resectability uncertain according to the decision of a local multidisciplinary consultation
Lesions measurable in 1 dimension by RECIST criteria (metastases and primary rectal cancer)
No rectal obstruction requiring surgery or the emergency fitting of a prosthesis
No CNS metastases

PATIENT CHARACTERISTICS:

WHO performance status 0-2
ANC ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Creatinine clearance ≥ 60 mL/min
Hemoglobin ≥ 10 g/dL (transfusions allowed)
FEV ≥ 50%
QT interval ≤ 450 ms (in men) or ≤ 470 ms (in women)
Total bilirubin ≤ 1.5 times upper limit of normal
Serum albumin ≥ 25 g/L
Not pregnant or nursing
Fertile patients must use effective contraception
No history of another cancer except for nonmelanoma skin cancer or curatively treated carcinoma in situ of the cervix
History of other cancers allowed provided the patient has been disease-free > 3 years
None of the following:
Congestive heart failure or coronary heart disease
Myocardial infarction within the past year
Uncontrolled hypertension (systolic BP > 160 mm Hg or diastolic BP > 100 mm Hg) despite optimal medical management
No active severe rectal bleeding
No liver failure
No known Gilbert syndrome
No severe uncontrolled infection
No chronic diarrhea, malabsorption syndrome, or intestinal obstruction/subocclusion
No severe uncontrolled pain (visual analogue scale 5/10) with morphine treatment
No other medical, psychological, or social condition that, in the investigator's opinion, could affect the patient's compliance with study treatment
No hypersensitivity to any component of study treatment

PRIOR CONCURRENT THERAPY:

See Patient Characteristics
No prior radiotherapy to the pelvis
More than 4 weeks since prior experimental therapy
More than 7 days since prior CYP3A4 inhibitor before the administration of sunitinib malate
More than 12 days since prior CYP3A4 inducer
No concurrent participation in another clinical study
No other concurrent anticancer therapy