RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. SU5416 may stop the growth of solid tumors by stopping blood flow to the tumor. Combining more than once chemotherapy drug with SU5416 may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of SU5416 combined with gemcitabine and cisplatin in treating patients who have advanced solid tumors.

Condition	Treatment or Intervention	Phase
unspecified adult solid tumor, protocol specific	Drug: cisplatin  Drug: gemcitabine  Drug: SU5416	Phase I

Further Study Details: 

OBJECTIVES: I. Assess the toxicities and pharmacokinetics of SU5416 when combined with gemcitabine and cisplatin in patients with advanced solid tumors.

II. Determine the antitumor activity of this combination treatment regimen in this patient population.

PROTOCOL OUTLINE: This is an open label, dose escalation study of SU5416.

Patients receive gemcitabine IV over 30 minutes followed by cisplatin IV over 1 hour on day 1; SU5416 IV over 70 minutes on day 4; gemcitabine IV over 30 minutes followed by SU5416 IV over 70 minutes on day 8, and SU5416 on days 11, 15, and 18. Treatment repeats every 3 weeks for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity. Following 6 courses of therapy, patients with stable and responsive disease may receive SU5416 alone on days 1, 4, 8, 11, 15, and 18 every 3 weeks for a maximum of 1 year.

Cohorts of 3-6 patients receive escalating doses of SU5416 until the maximum tolerated dose (MTD) is reached. The MTD is defined as the dose preceding that at which at least one third of the patients experience dose limiting toxicity.

Patients are followed at 1 month, and then every 3 months.

PROJECTED ACCRUAL: A total of 16-30 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically proven advanced solid tumor that may respond to gemcitabine an cisplatin therapy (e.g., esophagus, head and neck, breast, ovary, bladder, or non-small cell lung cancer)
• No brain metastases

--Prior/Concurrent Therapy--

• Biologic therapy: At least 2 weeks since prior epoetin alfa, filgrastim (G-CSF), or sargramostim (GM-CSF); No prior antiangiogenesis therapy; No prior SU5416; No concurrent immunotherapy
• Chemotherapy: See Disease Characteristics; No more than 1 prior systemic chemotherapy regimen allowed; At least 4 weeks since prior systemic chemotherapy (6 weeks for mitomycin or nitrosourea); No prior high dose chemotherapy; At least 6 months since prior gemcitabine and cisplatin and responsive; No other concurrent chemotherapy
• Endocrine therapy: Not specified
• Radiotherapy: Not specified
• Surgery: At least 4 weeks since prior surgery
• Other: No other concurrent investigational agents

--Patient Characteristics--

• Age: 18 and over
• Performance status: ECOG 0-2
• Life expectancy: At least 12 weeks
• Hematopoietic: Absolute neutrophil count at least 1,500/mm3; Platelet count at least 100,000/mm3; Hemoglobin at least 8.8 g/dL
• Hepatic: Bilirubin less than 2.05 mg/dL
• Renal: Creatinine no greater than 1.8 mg/dL OR Creatinine clearance at least 50 mL/min
• Cardiovascular: No prior myocardial infarction; No severe or unstable angina; No history of atherosclerotic coronary artery disease requiring coronary or peripheral artery bypass surgery or concurrent medication; No history of arrhythmias, hypertension, or deep venous thrombosis; No clinical evidence of severe peripheral vascular disease related to diabetes mellitus
• Pulmonary: No history of lung embolism
• Other: No known allergy to Cremophor or Cremophor based drug products; No contraindications to systemic gemcitabine or cisplatin therapy; No insulin dependent or noninsulin dependent diabetes mellitus with clinical evidence of diabetic ulcers; No other active malignancies except basal cell skin cancer or carcinoma in situ of the cervix; No other acute or chronic medical or psychiatric condition or laboratory abnormality that would preclude study; Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception

Study chairs or principal investigators

Lee S. Rosen,  Study Chair,  Jonsson Comprehensive Cancer Center   

Study ID Numbers:  CDR0000068000; UCLA-0002046; NCI-G00-1805; SUGEN-ND019901/SE5416.102
Record last reviewed:  July 2004
Last Updated:  October 13, 2004
Record first received:  July 5, 2000
ClinicalTrials.gov Identifier:  NCT00005996
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08