PR-104 and Docetaxel or Gemcitabine in Treating Patients With Solid Tumors

Phase 1

Completed

• Conditions: Unspecified Adult Solid Tumor, Protocol Specific

• Registration Number: NCT00459836
• Lead Sponsor: Proacta, Incorporated

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as PR-104, docetaxel, and gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of PR-104 when given together with docetaxel or gemcitabine in treating patients with solid tumors.

Detailed Description

OBJECTIVES:

Primary

* Determine the maximum tolerated dose of PR-104 in combination with docetaxel or gemcitabine hydrochloride in patients with solid tumors.

Secondary

* Determine the safety of PR-104 in combination with docetaxel or gemcitabine hydrochloride in these patients.

* Determine the antitumor activity of these regimens using disease-specific parameters, such as exams, scans, and tumor markers, in these patients.

* Determine the pharmacokinetics of PR-104 and its alcohol metabolite in these patients.

* Determine the pharmacokinetics of docetaxel and gemcitabine hydrochloride when administered with PR-104.

* Collect plasma samples for assessment of potential biomarkers of tumor hypoxia from these patients.

* Examine metabolic changes in tumors using fludeoxyglucose F 18 positron emission tomography (PET) and PET imaging with fluoromisonidazole F 18 (a hypoxia-targeted radiopharmaceutical) in these patients.

OUTLINE: This is a nonrandomized, open-label, uncontrolled, multicenter, dose-escalation study of PR-104. Patients are assigned to 1 of 2 treatment groups according to patient's malignancy and prior treatment history.

* Group 1: Patients receive docetaxel IV over 60 minutes and PR-104 IV over 60 minutes on day 1.

* Group 2: Patients receive gemcitabine hydrochloride IV over 30 minutes and PR-104 IV over 60 minutes on days 1 and 8.

In both groups, treatment repeats every 21 days for up to 8 courses in the absence of unacceptable toxicity or disease progression.

Cohorts of 3-6 patients in each group receive escalating doses of PR-104 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 is collected at baseline and periodically during course 1 for pharmacokinetic analysis. Plasma samples are analyzed for biomarkers of tumor hypoxia at baseline and on days 2 and 8.

PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study.

Study Timeline

• Study Start: 2007-02
• Study First Submitted: 2007-04-11
• Study First Submitted QC: 2007-04-11
• Study First Posted: 2007-04-13
• Primary Completion: 2009-10
• Status Verified: 2011-02
• Last Update Submitted: 2011-02-28
• Last Update Posted: 2011-03-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 42

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Maximum tolerated dose of PR-104

Secondary Outcome Measures

Name	Time	Method
Safety of PR-104 as measured by CTCAE v3.0 criteria
Dose-limiting toxicity of PR-104
Pharmacokinetics of PR-104 and its alcohol metabolite in the blood
Pharmacokinetics of gemcitabine and docetaxel in the presence of PR-104
Antitumor activity

Trial Locations

Locations (3)

University of Auckland Cancer Center; 🇳🇿 Auckland, New Zealand

Waikato Hospital; 🇳🇿 Hamilton, New Zealand

Proacta, Incorporated; 🇺🇸 San Diego, California, United States