RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. PURPOSE: Phase I trial to study the effectiveness of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone in treating patients who have solid tumors that have not responded to previous treatment.

Condition	Treatment or Intervention	Phase
unspecified adult solid tumor, protocol specific	Drug: -aminopyridine-2-carboxaldehyde thiosemicarbazone	Phase I

OBJECTIVES: I. Determine the effects of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) in patients with solid tumors by evaluating the safety and tolerability, maximum tolerated dose (MTD) and recommended dose for Phase II studies, pharmacokinetics, and tumor response.

PROTOCOL OUTLINE: This is a dose escalation study. Patients receive 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) IV over 2 hours on days 1-5. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 1-6 patients receive escalating doses of 3-AP 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. Patients are followed for 4 weeks or until recovered.

PROJECTED ACCRUAL: Approximately 21 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically confirmed malignant solid tumor that has failed 1 or more conventional treatments or is unlikely to respond to currently available therapies
• No active CNS metastases

--Prior/Concurrent Therapy--

• Biologic therapy: Prior growth factor treatment allowed if blood counts normal
• Chemotherapy: At least 3 weeks since prior chemotherapy and recovered; At least 6 weeks since prior nitrosoureas or mitomycin and recovered; Prior hydroxyurea allowed and recovered
• Endocrine therapy: At least 2 weeks since prior hormonal therapy
• Radiotherapy: At least 3 weeks since prior radiotherapy and recovered; No prior radiotherapy to greater than 30% of the bone marrow
• Surgery: At least 2 weeks since any prior major surgery
• Other: At least 4 weeks since other prior investigational agents and recovered; No other concurrent investigational agents without consent of sponsor

--Patient Characteristics--

• Age: 18 and over
• Performance status: Karnofsky 70-100%
• Life expectancy: At least 3 months
• Hematopoietic: WBC greater than 3,000/mm3; Absolute neutrophil count at least 1,500/mm3; Platelet count greater than 100,000/mm3; Hemoglobin at least 10 g/dL
• Hepatic: Bilirubin less than 2.0 mg/dL; AST and ALT no greater than 3 times upper limit of normal (ULN); Alkaline phosphate no greater than 3 times ULN (no greater than 5 times ULN if liver metastases present)
• Renal: Creatinine less than 2.0 mg/dL
• Cardiovascular: No myocardial infarction within the past 3 months; No symptomatic coronary artery disease or heart block; No uncontrolled congestive heart failure
• Pulmonary: No moderate or severe pulmonary dysfunction
• Other: Not pregnant or nursing; Negative pregnancy test; Fertile women must use effective contraception; Body weight greater than 50 kg; No active infection; No mental deficits and/or psychiatric disorders that would preclude study; No other life-threatening illness; No bleeding disorder (except occult blood from gastrointestinal cancer)

Arizona
      Arizona Clinical Research Center, Tucson,  Arizona,  85712,  United States
Connecticut
      Yale Comprehensive Cancer Center, New Haven,  Connecticut,  06520-8028,  United States

Study chairs or principal investigators

Mario Sznol,  Study Chair,  Vion Pharmaceuticals   

Study ID Numbers:  CDR0000067390; VION-CLI-001-2; NCI-V99-1579
Record last reviewed:  April 2004
Record first received:  January 28, 2000
ClinicalTrials.gov Identifier:  NCT00004213
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-10-25