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PR104 and G-CSF in Treating Patients With Solid Tumors

Sponsor
Proacta, Incorporated (Industry)
Overall Status
Completed
CT.gov ID
NCT00616213
Collaborator
(none)
5
Enrollment
3
Locations
16
Duration (Months)
1.7
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease Intervention/Treatment Phase
  • Biological: filgrastim
  • Drug: PR104
  • Other: F-18-fluoromisonidazole
 Phase 1

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
5 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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
Study Start Date :
Feb 1, 2008
Actual Primary Completion Date :
Sep 1, 2008
Actual Study Completion Date :
Jun 1, 2009

Outcome Measures

Primary Outcome Measures

  1. Maximum tolerated dose of PR-104 [3 weeks (cycle 1)]

Secondary Outcome Measures

  1. Safety profile using CTCAE v3 criteria []

  2. Dose-limiting toxicity of PR-104 []

  3. Pharmacokinetics of PR-104 and its alcohol metabolite in blood []

  4. Anti-tumor activity []

  5. Biomarkers of tumor hypoxia []

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Locations

Site City State Country Postal Code
1 Virginia G. Piper Cancer Center at Scottsdale Healthcare - Shea Scottsdale Arizona United States 85258-4512
2 South Texas Accelerated Research Therapeutics San Antonio Texas United States 78229
3 Waikato Hospital Hamilton New Zealand 2020

Sponsors and Collaborators

  • Proacta, Incorporated

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
, ,
ClinicalTrials.gov Identifier:
NCT00616213
Other Study ID Numbers:
  • PR104-1004
  • PROACTA-PR-104-1004
First Posted:
Feb 15, 2008
Last Update Posted:
Jun 1, 2011
Last Verified:
May 1, 2011
Keywords provided by , ,
unspecified adult solid tumor, protocol specific
Additional relevant MeSH terms:
Neoplasms
Lenograstim

Study Results

No Results Posted as of Jun 1, 2011