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PR-104 and G-CSF in Treating Patients With Solid Tumors
This study is ongoing, but not recruiting participants.
First Received: February 14, 2008   Last Updated: February 6, 2009   History of Changes
Sponsored by: Proacta, Incorporated
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00616213
  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. 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.


Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Biological: filgrastim
Drug: PR-104
Other: 18F-fluoromisonidazole
Other: imaging biomarker analysis
Other: laboratory biomarker analysis
Other: pharmacological study
Phase I

MedlinePlus related topics: Cancer
Drug Information available for: Filgrastim
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Non-Randomized, 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 With Prophylactic G-CSF in Subjects With Solid Tumors

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

Primary Outcome Measures:
  • Maximum tolerated dose of PR-104 [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 21
Study Start Date: February 2008
Estimated Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Detailed Description:

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.

  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 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00616213

Locations
United States, Arizona
Virginia G. Piper Cancer Center at Scottsdale Healthcare - Shea
Scottsdale, Arizona, United States, 85258-4512
United States, Texas
South Texas Accelerated Research Therapeutics
San Antonio, Texas, United States, 78229
New Zealand
Waikato Hospital
Hamilton, New Zealand, 2020
Sponsors and Collaborators
Proacta, Incorporated
Investigators
Investigator: Kim Smith Proacta, Incorporated
  More Information

Additional Information:
No publications provided

Study ID Numbers: CDR0000584658, PROACTA-PR-104-1004
Study First Received: February 14, 2008
Last Updated: February 6, 2009
ClinicalTrials.gov Identifier: NCT00616213     History of Changes
Health Authority: United States: Food and Drug Administration

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

Study placed in the following topic categories:
Radiation-Sensitizing Agents
Ro 07-0741

Additional relevant MeSH terms:
Radiation-Sensitizing Agents
Ro 07-0741
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 07, 2009