PR104 and G-CSF in Treating Patients With Solid Tumors

Unspecified Adult Solid Tumor, Protocol Specific Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00616213
• Other study ID #: PR104-1004
• Secondary ID: PROACTA-PR-104-1
• Status: Completed
• Phase: Phase 1
• First received: February 14, 2008
• Last updated: May 31, 2011
• Start date: February 2008
• Est. completion date: June 2009

Study information

• Verified date: May 2011
• Source: Proacta, Incorporated
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5
• Est. completion date: June 2009
• Est. primary completion date: September 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

Biological:
• filgrastim
filgrastim will be administered at a standard dose and schedule

Drug:
• PR104
PR104 is administered intravenously once every 21 days

Other:
• F-18-fluoromisonidazole
F-18-fluoromisonidazole is administered intravenously prior to performance of PET scan

Locations

Country	Name	City	State
New Zealand	Waikato Hospital	Hamilton
United States	South Texas Accelerated Research Therapeutics	San Antonio	Texas
United States	Virginia G. Piper Cancer Center at Scottsdale Healthcare - Shea	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Proacta, Incorporated

Countries where clinical trial is conducted

United States,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose of PR-104		3 weeks (cycle 1)	Yes
Secondary	Safety profile using CTCAE v3 criteria			Yes
Secondary	Dose-limiting toxicity of PR-104			Yes
Secondary	Pharmacokinetics of PR-104 and its alcohol metabolite in blood			No
Secondary	Anti-tumor activity			No
Secondary	Biomarkers of tumor hypoxia			No