Metastatic colorectal cancer.
Conditions
Interventions
Product Code: su011248 L-malate salt
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: sunitinib malate
Current Sponsor code: SU011248
Sponsors
Pfizer Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed diagnosis of adenocarcinoma of the rectum or colon. 2. Metastatic disease, not amenable to curative surgery or radiation therapy. 3. Evidence of unidimensionally measurable disease as per RECIST. 4. Male or female, 18 years of age or older. 5. ECOG performance status 0 or 1. 6. Life expectancy : major than/equal to 12 weeks. 7. >6 months since completion of any adjuvant 5-FU (+/- oxaliplatin) chemotherapy. 8. No prior pelvic radiotherapy. 9. Adequate organ function as determined by the following criteria: • Serum aspartate aminotransferase (AST, serum glutamate-oxalate transferase [SGOT]) and serum alanine transferase (ALT serum glutamate-pyruvate transferase) [SGPT] less than/equal to 2.5 x ULN if no liver metastases present, less than/equal to 5 x ULN if liver metastases present • Total serum bilirubin less than/equal to 1.5 x ULN • Serum alkaline phosphatase =65 years) F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Prior treatment with chemotherapy or immunotherapy based regimens for metastatic disease. 2. Prior irradiation to >25% of the bone marrow (pelvic irradiation = 25%). 3. Prior surgery or radiation within 4 weeks prior to first day of SU011248 administration, except palliative radiotherapy to metastatic lesion. 4. Treatment with anticonvulsant agents or ongoing treatment with therapeutic doses of coumarin derivative anticoagulants (e.g. coumadin, warfarin, phenprocoumon) currently or within 2 weeks prior to first day of SU011248 administration. Low dose coumadin for DVT prophylaxis is permitted (up to 2 mg/day). 5. Current treatment on another clinical trial. 6. History of or known brain metastases, spinal cord compression or carcinomatous meningitis or new evidence of brain or leptomeningeal disease (baseline brain imaging required only in case of clinical suspicion of central nervous system metastases). 7. Any of the following within 12 months prior to first day of SU011248 dosing: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident including transient ischemic attack or a pulmonary embolism. 8. NCI CTCAE Grade 3 hemorrhage 150/100 mm Hg) that cannot be controlled with standard antihypertensive agents. 10. Ongoing cardiac dysrhythmias of NCI CTAE Grade ? 2, atrial fibrillation of any grade, prolongation of the QTC interval to >450 msec for males or ? 470 msec for females, or history of Torsade de pointes. 11. Known dihydropyrimidine dehydrogenase deficiency. 12. History of severe hypersensitivity reaction to 5-FU or irinotecan 13. Known human immunodeficiency virus (HIV)-or acquired immunodeficiency syndrome (AIDS)-related illness. 14. Diagnosis of any other primary malignancy within the last three years, except for adequately treated basal cell carcinoma squamous cell skin cancer or in situ carcinoma of the cervix uteri with no evidence of recurrent disease for 12 months. 15. Pregnancy or breastfeeding. All female patients with reproductive potential must have a negative pregnancy test (serum or urine) within 7 days prior to first dose of SU011248. 16. Other severe, acute or chronic medical or psychiatric conditions, or laboratory abnormalities that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results and in the judgment of the investigator would make the patient inappropriate for entry into this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the Maximum Tolerated Dose (MTD) and overall safety and tolerability of SU011248 in combination with FOLFIRI; Secondary Objective: • To assess the plasma pharmacokinetic parameters of SU011248 (and its metabolite SU012662), irinotecan (and its metabolite SN-38) and 5-FU when these drugs are co-administered. • To assess preliminary anti-tumor activity of SU011248 and FOLFIRI when given in combination ;Primary end point(s): Objective Response Rate (ORR) | — |
Countries
United Kingdom
Outcome results
None listed