RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of combining 3-AP, cisplatin, and paclitaxel in treating patients who have advanced or metastatic cancer.

Condition	Treatment or Intervention	Phase
unspecified adult solid tumor, protocol specific	Procedure: chemotherapy  Drug: 3-AP  Drug: cisplatin  Drug: paclitaxel	Phase I

Further Study Details: 

OBJECTIVES: I. Determine the safety and tolerability of 3-AP, cisplatin, and paclitaxel in patients with advanced or metastatic cancer. II. Determine the toxic effects of this regimen in these patients. III. Determine the maximum tolerated dose and recommended phase II dose of this regimen in these patients. IV. Determine the pharmacokinetic parameters of this regimen in these patients. V. Determine the tumor response in patients treated with this regimen.

PROTOCOL OUTLINE: This is a dose-escalation study. Patients receive 3-AP IV continuously over 96 hours on days 1-4 and paclitaxel IV over 3 hours followed by cisplatin IV over 1 hour on day 3. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients achieving complete response (CR) receive 1 additional course of therapy after documented CR. Patients with partial response or stable disease may receive therapy for up to 6 months. Cohorts of 1-6 patients receive escalating doses of 3-AP, paclitaxel, and cisplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: Approximately 25-30 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed progressive advanced or metastatic cancer; Failed 1 or more prior standard therapies for disease OR Unlikely to respond to any currently available therapies
• Measurable or evaluable disease
• No active CNS metastases; Previously treated CNS metastases allowed if no evidence of new CNS metastases and stable for at least 2 months

--Prior/Concurrent Therapy--

• Biologic therapy: Concurrent hematopoietic growth factors allowed except if used prophylactically during first course of study therapy
• Chemotherapy: More than 3 weeks since prior chemotherapy (6 weeks for nitrosourea or mitomycin) and recovered; More than 6 months since prior combination cisplatin and paclitaxel; Prior cisplatin or paclitaxel as single agents allowed; Prior 3-AP allowed
• Endocrine therapy: Not specified
• Radiotherapy: More than 3 weeks since prior radiotherapy and recovered; Concurrent radiotherapy to a single site of progressive disease allowed if site requires treatment within the first course of study therapy
• Surgery: Not specified
• Other: More than 3 weeks since any therapy for malignancy and recovered; No other concurrent investigational drugs without consent of sponsor

--Patient Characteristics--

• Age: 18 and over
• Performance status: ECOG 0-1
• Life expectancy: More than 3 months
• Hematopoietic: Absolute neutrophil count at least 1,500/mm3; Platelet count at least 100,000/mm3; Hemoglobin at least 10 g/dL (transfusion allowed); No active bleeding or coagulation disorder (occult blood for gastrointestinal cancer allowed)
• Hepatic: Bilirubin no greater than 1.5 mg/dL; ALT/AST no greater than 3 times upper limit of normal (ULN) (5 times ULN if liver metastases present); Alkaline phosphatase no greater than 3 times ULN (5 times ULN if liver metastases present); Albumin at least 3.0 g/dL; PT/PTT no greater than 1.5 times ULN
• Renal: Creatinine no greater than 1.5 mg/dL
• Cardiovascular: No active heart disease; No myocardial infarction within the past 3 months; No symptomatic coronary artery disease, heart block, or uncontrolled congestive heart failure
• Pulmonary: No moderate to severe compromise in pulmonary function
• Other: No mental deficits and/or psychiatric history that would preclude study; No active infection; No pre-existing severe hearing impairment; No pre-existing grade 2 or greater neuropathy; No prior severe allergic reaction to study drugs; No other life-threatening illness; No chronic toxic effects from prior chemotherapy greater than grade I; Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception during and for 18 months after study

New York
      Albert Einstein Comprehensive Cancer Center, Bronx,  New York,  10461,  United States
      New York Presbyterian Hospital - Cornell Campus, New York,  New York,  10021,  United States

Study chairs or principal investigators

Mario Sznol,  Study Chair,  Vion Pharmaceuticals   

Study ID Numbers:  CDR0000068591; VION-CLI-015; NCI-V01-1658; AECM-1200012380
Record last reviewed:  September 2003
Last Updated:  October 13, 2004
Record first received:  June 6, 2001
ClinicalTrials.gov Identifier:  NCT00016874
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08