Clinical trial NCT00390052: 3-AP in Treating Patients With Advanced or Metastatic Solid Tumors
Official title: A Phase I and Pharmacokinetic Study of Oral 3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone(3-AP,Triapine) in the Treatment of Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Unspecified Adult Solid Tumor, Protocol Specific
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2006-10-19
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase I trial is studying the side effects and best dose of 3-AP in treating patients with advanced or metastatic solid tumors. 3-AP may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed description: OBJECTIVES:

I. Determine the safety, tolerability, and toxicity of oral 3-AP in patients with advanced solid tumors.

II. Determine the maximum tolerated dose and recommended phase II dose of this drug in these patients.

III. Determine the oral bioavailability and pharmacokinetics of this drug. IV. Assess tumoral expression of genes involved in response and resistance to 3-AP.

V. Observe and record any tumor response in these patients.

OUTLINE: This is a multicenter, dose-escalation study.

Patients receive a one time dose of 3-AP IV over 2 hours on day -7. Patients then receive oral 3-AP twice daily on days 1-3, 8-10, and 15-17. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of oral 3-AP until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Blood samples for pharmacokinetic analysis are collected periodically over 8 hours after the IV dose of 3-AP and after the first oral dose of 3-AP during course 1.

After completion of study treatment, patients are followed periodically.

Eligibility criteria: Criteria:

* Must be able to swallow
* Histologically confirmed solid tumor
* Advanced or metastatic disease
* Measurable or evaluable disease
* No known active CNS metastases
* ECOG performance status 0-1
* Life expectancy \> 3 months
* Progressive disease during \>= 1 prior standard therapy OR disease unlikely to respond to any currently available therapies
* Patients with previously treated CNS metastases who have no evidence of new CNS metastases AND are stable for \>= 2 months are eligible
* Platelet count \>= 100,000/mm\^3
* Hemoglobin \>= 10 g/dL (transfusions allowed)
* Absolute neutrophil count \>= 1,500/mm\^3
* ALT and AST =\< 2.5 times upper limit of normal (ULN)
* Alkaline phosphatase =\< 2.5 times ULN
* Creatinine =\< 1.5 mg/dL OR creatinine clearance \>= 50 mL/min
* Bilirubin normal
* PT/PTT =\< 1.5 times ULN
* FEV1 \>= 1.2 L
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception 2 weeks prior to and during study treatment
* No mental deficits and/or psychiatric history that may preclude study treatment
* No active heart disease, including any of the following: myocardial infarction within the past 3 months, symptomatic coronary artery disease or heart block, uncontrolled congestive heart failure
* No moderate to severe compromise of pulmonary function
* No active infection
* No other life-threatening illness
* No active coagulation disorder other than occult blood
* No known positivity for glucose-6-phosphate dehydrogenase (G6PD) deficiency
* Recovered from prior treatment
* Prior gemcitabine allowed
* More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
* More than 3 weeks since prior radiotherapy or any other treatment for this cancer
* No prior 3-AP
* No concurrent radiotherapy
* No other concurrent investigational agent

Primary outcomes:
measure: Maximum tolerated dose of oral 3-AP determined by dose-limiting toxicities graded according to the NCI CTCAE version 3.0
timeFrame: 28 days
Secondary outcomes:
measure: Serum pharmacokinetics of oral triapine
timeFrame: Baseline, day 4, and day 8
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
Study officials:
affiliation: City of Hope Medical Center
name: Yun Yen
role: PRINCIPAL_INVESTIGATOR
References: