PR-104 in Treating Patients With Advanced Solid Tumors

November 29, 2012 updated by: Proacta, Incorporated

A Phase I, Multi-Center, Open Label, Dose Escalation Trial of the Safety and Pharmacokinetics of Intravenous PR-104 Given Every 3 Weeks in Patients With Solid Tumors

RATIONALE: Drugs used in chemotherapy, such as PR-104, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase I trial is studying the side effects and best dose of PR-104 in treating patients with advanced solid tumors.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Evaluate the safety and tolerability of PR-104 in patients with advanced solid tumors.
  • Determine the maximum tolerated dose of PR-104 in these patients.

Secondary

  • Characterize the pharmacokinetics of PR-104 and its alcohol metabolite in these patients.
  • Assess evidence of antitumor activity of this drug in these patients.

Tertiary

  • Examine metabolic changes in tumors of these patients using fludeoxyglucose F 18 positron emission tomography scanning.

OUTLINE: This is a multicenter, open-label, prospective, uncontrolled, dose-escalation study.

Patients receive PR-104 IV over 60 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients 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 then periodically during study treatment for pharmacokinetic and tumor marker studies. Patients undergo fludeoxyglucose F 18 positron emission tomography scanning before beginning study treatment and after completion of course 2 to assess metabolic activity of the tumor.

After completion of study treatment, patients are followed at 30 days.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Study Type

Interventional

Enrollment (Actual)

27

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90095-1781
        • Jonsson Comprehensive Cancer Center at UCLA

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed solid tumor, meeting 1 of the following criteria:

    • Not amenable to standard therapy
    • Refractory to conventional therapy
  • Measurable or evaluable disease

PATIENT CHARACTERISTICS:

  • Karnofsky performance status 70-100%
  • Life expectancy > 3 months
  • Absolute neutrophil count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Hemoglobin > 9 g/L (transfusion independent)
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • ALT and AST ≤ 2.5 times ULN
  • Creatinine clearance ≥ 60 mL/min
  • PT/INR or aPTT ≤ 1.1 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 30 days after completion of study treatment

  • No significant cardiac comorbidity including any of the following:

    • New York Heart Association class III-IV congenital heart failure
    • LVEF < 40%
    • Unstable angina
    • Myocardial infarction within the past 6 months
    • Ventricular arrhythmias requiring drug therapy
    • Pacemaker or implanted defibrillator
  • No ongoing coagulopathy
  • No uncontrolled infection or infection requiring parenteral antibiotics
  • No other significant clinical disorder or laboratory finding that would preclude study treatment
  • No known HIV positivity
  • No known positivity for hepatitis B surface antigen or hepatitis C with abnormal liver tests
  • No known allergy to nonplatinum-containing alkylating agents

PRIOR CONCURRENT THERAPY:

  • Recovered from prior therapy
  • More than 2 weeks since prior hormonal therapy (except for androgen-deprivation therapy)
  • More than 4 weeks since prior major surgery
  • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
  • More than 4 weeks since prior radiotherapy
  • More than 1 month since prior investigational drugs, therapies, or devices
  • No prior radiotherapy to > 25% of bone marrow
  • No prior high-dose chemotherapy, either myeloablative or nonmyeloablative (mini-allogeneic transplant)
  • No more than 3 prior myelosuppressive chemotherapy regimens

  • Concurrent steroids allowed provided dose is stable for ≥ 2 weeks and clinical condition is stable for 1 month

    • Nasal, opthalmologic, and topical glucocorticoid preparations allowed
    • Physiologic hormone replacement therapies allowed (i.e., oral replacement glucocorticoid therapy for adrenal insufficiency)
  • No concurrent prophylactic hematopoietic growth factors

  • No concurrent radiotherapy, including local palliative radiotherapy or systemic radioisotopes

    • Radioisotopes for protocol specified positron emission tomography allowed
  • No other concurrent investigational agents
  • No other concurrent chemotherapy, radiotherapy (including palliative local radiotherapy), hormonal therapy (except for androgen-deprivation therapy), and/or biological therapy (including immunotherapy)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: PR-104
PR104 was administered as a 1-hr IV infusion every 21 days at doses ranging from 135 to 1400 mg/m2
Other: pharmacological study
Other: laboratory biomarker analysis
Drug: PR-104

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Proacta, Incorporated

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Mark D. Pegram, MD, Jonsson Comprehensive Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2005

Primary Completion (Actual)

June 1, 2007

Study Completion (Actual)

June 1, 2007

Study Registration Dates

First Submitted

July 5, 2006

First Submitted That Met QC Criteria

July 5, 2006

First Posted (Estimate)

July 6, 2006

Study Record Updates

Last Update Posted (Estimate)

November 30, 2012

Last Update Submitted That Met QC Criteria

November 29, 2012

Last Verified

November 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PR104-1001
  • P30CA016042 (U.S. NIH Grant/Contract)
  • UCLA-0512034-01A
  • PROACTA-PR-104-1001

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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