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)
18 Years
N/A
Both
Colorectal Cancer, Metastatic Cancer
Trial Information
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)
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.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Response rate at 3 months as assessed by RECIST criteria
Safety Issue:
No
Principal Investigator
Philippe Rougier, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Hopital Ambroise Pare
Authority:
Unspecified
Study ID:
CDR0000637832
NCT ID:
NCT00936832
Start Date:
April 2009
Completion Date:
Related Keywords:
- Colorectal Cancer
- Metastatic Cancer
- stage IV rectal cancer
- adenocarcinoma of the rectum
- liver metastases
- lung metastases
- Rectal Neoplasms
- Colorectal Neoplasms
- Neoplasm Metastasis
- Neoplasms
- Neoplasms, Second Primary
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