PR104 and G-CSF in Treating Patients With Solid Tumors

This study has been completed.
Sponsor:
Information provided by:
Proacta, Incorporated
ClinicalTrials.gov Identifier:
NCT00616213
First received: February 14, 2008
Last updated: May 31, 2011
Last verified: May 2011

February 14, 2008
May 31, 2011
February 2008
September 2008   (final data collection date for primary outcome measure)
Maximum tolerated dose of PR-104 [ Time Frame: 3 weeks (cycle 1) ] [ Designated as safety issue: Yes ]
Maximum tolerated dose of PR-104 [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00616213 on ClinicalTrials.gov Archive Site
  • Safety profile using CTCAE v3 criteria [ Designated as safety issue: Yes ]
  • Dose-limiting toxicity of PR-104 [ Designated as safety issue: Yes ]
  • Pharmacokinetics of PR-104 and its alcohol metabolite in blood [ Designated as safety issue: No ]
  • Anti-tumor activity [ Designated as safety issue: No ]
  • Biomarkers of tumor hypoxia [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
PR104 and G-CSF in Treating Patients With Solid Tumors
A Phase I, Multi-Center, Open-Label, Dose Escalation Trial of the Safety and Pharmacokinetics of Intravenous PR104 Given With Prophylactic G-CSF in Subjects 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. Colony-stimulating factors, such as G-CSF, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. Giving PR-104 together with G-CSF 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 G-CSF in treating patients with solid tumors.

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose of PR-104 in combination with filgrastim (G-CSF) in patients with solid tumors.

Secondary

  • Characterize the safety of this regimen in these patients.
  • Evaluate the pharmacokinetics of PR-104 and its alcohol metabolite.
  • Evaluate the rate of hypoxia in various solid tumors using F-MISO PET (18F-fluoromisonidazole positron emission tomography) imaging.
  • Assess for antitumor toxicity in these patients.
  • Collect plasma samples for the assessment of potential biomarkers of tumor hypoxia.

OUTLINE: This is a multicenter, dose-escalation study of PR-104.

Patients receive PR-104 IV over 1 hour on day 1 and filgrastim (G-CSF) on day 2. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo 18F-fluoromisonidazole PET scans at baseline and prior to course 3 to assess tumor hypoxia.

Patients undergo blood sample collection periodically during course 1. Samples are analyzed for the pharmacokinetics of PR-104 and for identification of biomarkers for tumor hypoxia.

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

Interventional
Phase 1
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Unspecified Adult Solid Tumor, Protocol Specific
  • Biological: filgrastim
    filgrastim will be administered at a standard dose and schedule
    Other Names:
    • Neupogen
    • G-CSF
  • Drug: PR104
    PR104 is administered intravenously once every 21 days
    Other Name: PR-104
  • Other: F-18-fluoromisonidazole
    F-18-fluoromisonidazole is administered intravenously prior to performance of PET scan
    Other Name: FMISO
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
5
June 2009
September 2008   (final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed solid tumors
  • Measurable or evaluable disease

PATIENT CHARACTERISTICS:

Inclusion criteria:

  • ECOG performance status 0-1
  • Absolute neutrophil count ≥ 1.5 x 10^9/L
  • Platelet count ≥ 100 x 10^9/L
  • Hemoglobin ≥ 9 g/dL (no red blood cell transfusions allowed)
  • Serum bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • PTT ≤ 1.5 times normal
  • Serum creatinine ≤ 1.5 times ULN
  • ALT or AST ≤ 2 times ULN (≤ 5 times ULN if liver metastases are present)
  • Not pregnant or nursing
  • Fertile patients must use effective contraception during and for 30 days after completion of study therapy
  • Able to read, understand, and provide written informed consent

Exclusion criteria:

  • Evidence of a significant medical disorder or laboratory finding that, in the opinion of the investigator, compromises the patient's safety during study participation, including any of the following:

    • Uncontrolled infection or infection requiring a concomitant parenteral antibiotic
    • Uncontrolled diabetes
    • Congestive heart failure
    • Myocardial infarction within the past 6 months
    • Chronic renal disease
    • Coagulopathy (excluding prophylactic anticoagulation)
  • Known HIV positivity
  • Hepatitis B sAg-positive or known to be hepatitis C-positive with abnormal liver function tests

PRIOR CONCURRENT THERAPY:

  • No more than 3 prior myelosuppressive chemotherapy regimens

    • Patients who have received more than 3 prior myelosuppressive regimens may be eligible, if considered to have adequate marrow, based on prior exposure to 1 of the following regimens:

      • Minimally myelosuppressive regimens
      • Limited courses of myelosuppressive regimens
  • More than 4 weeks since prior and no other concurrent licensed or investigational anticancer treatment (6 weeks for nitrosoureas or mitomycin C)
  • More than 24 hours since any prior radiotherapy and no likelihood of toxicity from this therapy
  • More than 4 weeks since major surgery
  • No prior radiotherapy to > 20% of bone marrow
  • No prior high-dose chemotherapy (including either myeloablative or non-myeloablative transplantations)
  • Prior and concurrent androgen deprivation therapy allowed
  • Concurrent systemic steroids allowed, provided the patient has been on a stable dose for at least 2 weeks prior to first dose of PR-104
  • No concurrent irradiation therapy (palliative or therapeutic), unless given in the absence of tumor progression
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   New Zealand
 
NCT00616213
PR104-1004, PROACTA-PR-104-1004
Not Provided
Brenda Gibson, Assoc. Director, Proacta, Inc.
Proacta, Incorporated
Not Provided
Not Provided
Proacta, Incorporated
May 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP