Clinical Trial: 3-AP in Treating Patients With Advanced Cancer


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Sponsored by:	Vion Pharmaceuticals
Information provided by:	National Cancer Institute (NCI)

Condition	Treatment or Intervention	Phase
unspecified adult solid tumor, protocol specific	Drug: -AP	Phase I

OBJECTIVES: I. Determine the safety, tolerability, and toxicity of 3-AP in patients with advanced malignancies. II. Determine the maximum tolerated dose and recommended phase II dose of this treatment in these patients. III. Determine the pharmacokinetic parameters of this treatment in these patients. IV. Determine the tumor response in these patients treated with this regimen.

PROTOCOL OUTLINE: This is a dose escalation, multicenter study. Patients receive 3-AP IV continuously over 96 hours. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients with complete response receive treatment for 1 course past the course in which the complete response was documented; patients with partial response may receive treatment for up to 1 year; and patients with stable disease may receive treatment for up to 6 months. During the accelerated phase of the study, cohorts of 1 patient each receive escalating doses of 3-AP until one patient experiences dose limiting toxicity (DLT) or 2 different patients experience grade 2 toxicity during any course. When the accelerated phase ends, cohorts of 3-6 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 DLT.

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

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

Histologically confirmed advanced or metastatic malignancy; Failed one or more prior standard therapies or considered unlikely to respond to any currently available therapy
Measurable or evaluable disease
No active, untreated CNS metastases (stable for at least 2 months and no evidence of new CNS metastases)

--Prior/Concurrent Therapy--

Biologic therapy: Not specified
Chemotherapy: At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered; No persistent chronic toxicity from prior chemotherapy greater than grade 1
Endocrine therapy: Not specified
Radiotherapy: At least 3 weeks since prior radiotherapy; Concurrent radiotherapy to single site of progressive disease allowed during first course of study treatment
Surgery: Not specified
Other: At least 3 weeks since any prior treatment for malignancy and recovered; No other concurrent investigational drug

--Patient Characteristics--

Age: 18 and over
Performance status: ECOG 0-1
Life expectancy: Greater 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 bleeding disorder (except occult blood for gastrointestinal cancers)
Hepatic: Bilirubin no greater than 2.0 mg/dL; ALT, AST, and alkaline phosphatase no greater than 3 times upper limit of normal (ULN) (no greater than 5 times ULN with liver metastases); PT and PTT no greater than 1.5 times ULN
Renal: Creatinine no greater than 2.0 mg/dL
Cardiovascular: No active heart disease; No myocardial infarction within the past 3 months; No symptomatic coronary artery disease or heart block; No uncontrolled congestive heart failure
Pulmonary: No moderate to severe compromise of pulmonary function
Other: No active infection; No mental deficits and/or psychiatric history that would preclude study; No other concurrent life threatening illness; Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception during and for 18 months after study

Mario Sznol, Study Chair, Vion Pharmaceuticals