3-AP in Treating Patients With Advanced or Metastatic Solid Tumors

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

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.

Study Overview

• Status: Completed
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Drug: triapine; Other: pharmacological study; Procedure: laboratory biomarker analysis

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I; Patients will receive a 2-hour infusion of 3-AP once in week 1. Beginning in week 2, they will receive 3-AP by mouth twice a day 3 days a week for 3 weeks. Treatment with 3-AP by mouth may repeat every 4 weeks for as long as benefit is shown.	Drug: triapine; Given IV and orally; Other Names: 3-AP; OCX-191; Other: pharmacological study; correlative study; Other Names: pharmacological studies; Procedure: laboratory biomarker analysis; Correlative study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum tolerated dose of oral 3-AP determined by dose-limiting toxicities graded according to the NCI CTCAE version 3.0	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum pharmacokinetics of oral triapine	Summary statistics of the pharmacokinetic parameters will be tabulated using the logarithmic scale where appropriate. The relationship of the AUC to the dose will be assessed by least-square regression analysis.	Baseline, day 4, and day 8

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Yun Yen, City of Hope Medical Center

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): February 1, 2011

Study Registration Dates

• First Submitted: October 18, 2006
• First Submitted That Met QC Criteria: October 18, 2006
• First Posted (Estimate): October 19, 2006

Study Record Updates

• Last Update Posted (Estimate): December 16, 2013
• Last Update Submitted That Met QC Criteria: December 13, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: NCI-2009-00139 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U01CA062505 (U.S. NIH Grant/Contract); PHI-52 (Other Identifier: City of Hope); CDR0000507731; 7225 (Other Identifier: CTEP)