PR104 and G-CSF in Treating Patients With Solid Tumors

Proacta

Status and phase: Completed; Phase 1

Conditions: Unspecified Adult Solid Tumor, Protocol Specific

Treatments: Drug: PR104; Biological: filgrastim; Other: F-18-fluoromisonidazole

Study type: Interventional

Funder types: Industry

Identifiers

NCT00616213

PROACTA-PR-104-1004

PR104-1004

Details and patient eligibility

About

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.

Full 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.

Enrollment: 5 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)