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A Phase I and Pharmacokinetic Study of Oral 3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone(3-AP,Triapine) in the Treatment of Advanced Solid Tumors


Phase 1
18 Years
N/A
Not Enrolling
Both
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

A Phase I and Pharmacokinetic Study of Oral 3-Aminopyridine-2-Carboxaldehyde Thiosemicarbazone(3-AP,Triapine) in the Treatment of Advanced Solid Tumors


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose of oral 3-AP determined by dose-limiting toxicities graded according to the NCI CTCAE version 3.0

Outcome Time Frame:

28 days

Safety Issue:

Yes

Principal Investigator

Yun Yen

Investigator Role:

Principal Investigator

Investigator Affiliation:

City of Hope Medical Center

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-00139

NCT ID:

NCT00390052

Start Date:

December 2006

Completion Date:

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • Neoplasms

Name

Location
City of Hope Medical Center Duarte, California  91010