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PR-104 in Treating Patients With Advanced Solid Tumors
This study is ongoing, but not recruiting participants.
Sponsors and Collaborators: Jonsson Comprehensive Cancer Center
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00349167
  Purpose

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.


Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Drug: PR-104
Procedure: laboratory biomarker analysis
Procedure: pharmacological study
Phase I

MedlinePlus related topics: Cancer
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Open Label, Uncontrolled
Official Title: 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

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Frequency, type, and severity of adverse effects [ Designated as safety issue: Yes ]
  • Incidence of serious adverse effects [ Designated as safety issue: Yes ]
  • Incidence of clinically significant or extraordinary laboratory findings [ Designated as safety issue: No ]
  • Incidence of dose-limiting toxicity [ Designated as safety issue: Yes ]
  • Pharmacokinetics and pharmacodynamics [ Designated as safety issue: No ]
  • Overall tumor bulk and measurable disease by RECIST criteria [ Designated as safety issue: No ]
  • Best overall clinical response [ Designated as safety issue: No ]
  • Duration of response [ Designated as safety issue: No ]
  • Time to disease progression [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Metabolic activity by fludeoxyglucose F 18 positron emission tomography [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: February 2006
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00349167

Locations
United States, California
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, United States, 90095-1781
Sponsors and Collaborators
Jonsson Comprehensive Cancer Center
Investigators
Principal Investigator: Mark D. Pegram, MD Jonsson Comprehensive Cancer Center
  More Information

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Study ID Numbers: CDR0000480394, UCLA-0512034-01A, PROACTA-PR-104-1001
Study First Received: July 5, 2006
Last Updated: July 23, 2008
ClinicalTrials.gov Identifier: NCT00349167  
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
unspecified adult solid tumor, protocol specific

ClinicalTrials.gov processed this record on January 14, 2009