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

Phase 1

Completed

• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Interventions: Drug: triapine; Other: pharmacological study; Procedure: laboratory biomarker analysis

• Registration Number: NCT00390052
• Lead Sponsor: National Cancer Institute (NCI)

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.

Study Timeline

• Study First Submitted: 2006-10-18
• Study First Submitted QC: 2006-10-18
• Study First Posted: 2006-10-19
• Study Start: 2006-12
• Primary Completion: 2011-02
• Status Verified: 2013-12
• Last Update Submitted: 2013-12-13
• Last Update Posted: 2013-12-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm I	triapine	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.
Arm I	pharmacological study	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.
Arm I	laboratory biomarker analysis	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.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Serum pharmacokinetics of oral triapine	Baseline, day 4, and day 8	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.

Trial Locations

Locations (1)

City of Hope; 🇺🇸 Duarte, California, United States