3-AP Plus Cisplatin and Paclitaxel in Treating Patients With Advanced or Metastatic Cancer

Study Overview
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Brief Summary
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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.

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

Official Title
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A Phase I Study Of 3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone (3-AP, Triapine) In Combination With Cisplatin And Paclitaxel In Patients With Advanced And Metastatic Cancer

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: cisplatin
* Drug: paclitaxel
* Drug: triapine


Participation Criteria
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Eligibility Criteria
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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 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/mm^3 Platelet count at least 100,000/mm^3 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 participation 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: cisplatin|nan|
|Drug: paclitaxel|nan|
|Drug: triapine|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unspecified adult solid tumor, protocol specific