PR-104 and Docetaxel or Gemcitabine in Treating Patients With Solid Tumors

Unspecified Adult Solid Tumor, Protocol Specific Clinical Trial

Official title:

A Phase Ib, Multi-Center, Open-Label, Dose Escalation Trial of Intravenous PR-104 Given in Combination With Docetaxel or Gemcitabine in Subjects With Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00459836
• Other study ID #: PR104-1003
• Secondary ID: PROACTA-PR-104-1
• Status: Completed
• Phase: Phase 1
• First received: April 11, 2007
• Last updated: February 28, 2011
• Start date: February 2007

Study information

• Verified date: February 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, docetaxel, and gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) 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 docetaxel or gemcitabine in treating patients with solid tumors.

Description:

OBJECTIVES:

Primary

• Determine the maximum tolerated dose of PR-104 in combination with docetaxel or gemcitabine hydrochloride in patients with solid tumors.

Secondary

• Determine the safety of PR-104 in combination with docetaxel or gemcitabine hydrochloride in these patients.

• Determine the antitumor activity of these regimens using disease-specific parameters, such as exams, scans, and tumor markers, in these patients.

• Determine the pharmacokinetics of PR-104 and its alcohol metabolite in these patients.

• Determine the pharmacokinetics of docetaxel and gemcitabine hydrochloride when administered with PR-104.

• Collect plasma samples for assessment of potential biomarkers of tumor hypoxia from these patients.

• Examine metabolic changes in tumors using fludeoxyglucose F 18 positron emission tomography (PET) and PET imaging with fluoromisonidazole F 18 (a hypoxia-targeted radiopharmaceutical) in these patients.

OUTLINE: This is a nonrandomized, open-label, uncontrolled, multicenter, dose-escalation study of PR-104. Patients are assigned to 1 of 2 treatment groups according to patient's malignancy and prior treatment history.

• Group 1: Patients receive docetaxel IV over 60 minutes and PR-104 IV over 60 minutes on day 1.

• Group 2: Patients receive gemcitabine hydrochloride IV over 30 minutes and PR-104 IV over 60 minutes on days 1 and 8.

In both groups, treatment repeats every 21 days for up to 8 courses in the absence of unacceptable toxicity or disease progression.

Cohorts of 3-6 patients in each group receive escalating doses of PR-104 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Blood is collected at baseline and periodically during course 1 for pharmacokinetic analysis. Plasma samples are analyzed for biomarkers of tumor hypoxia at baseline and on days 2 and 8.

PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. primary completion date: October 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed solid tumor malignancy

• Treatment with either docetaxel or gemcitabine hydrochloride in combination with an investigational agent is reasonable

• Measurable or evaluable disease

PATIENT CHARACTERISTICS:

• ECOG performance status of 0-1

• Absolute neutrophil count = 1,500/mm³

• Platelet count = 100,000/mm³

• Hemoglobin = 9.0 g/dL (red blood cell transfusion allowed)

• Bilirubin normal

• ALT and AST = 2.5 times upper limit of normal (ULN)

• Creatinine = 1.5 times ULN

• PT/INR or aPTT = 1.1 times ULN

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 30 days after completion of study therapy

• No evidence of any other significant medical disorder, including uncontrolled infection or infection requiring a concurrent parenteral antibiotic, or laboratory finding that, in the opinion of the investigator, would preclude study compliance

• No known HIV positivity

• No hepatitis B surface antigen positivity

• No hepatitis C positivity with abnormal liver function test

PRIOR CONCURRENT THERAPY:

• No prior radiotherapy to > 25% of bone marrow

• No prior high-dose chemotherapy (including conditioning for either myeloablative or nonmyeloablative transplantation)

• No more than 3 prior chemotherapy regimens

• More than 4 weeks since prior major surgery

• More than 4 weeks since prior investigational or traditional anticancer therapy (including radiotherapy) (6 weeks for nitrosoureas and mitomycin C)

• The following medications/treatments are not permitted during the trial:

• Any other licensed or investigational anticancer treatment

• Prophylactic hematopoietic growth factors

• Irradiation therapy (palliative or therapeutic) unless given in the absence of tumor progression

• Concurrent systemic steroids allowed provided the patient is on a stable dose for = 2 weeks prior to study treatment

• Concurrent androgen-deprivation therapy allowed

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

Drug:
• PR-104

• docetaxel

• gemcitabine hydrochloride

Other:
• laboratory biomarker analysis

• pharmacological study

Locations

Country	Name	City	State
New Zealand	University of Auckland Cancer Center	Auckland
New Zealand	Waikato Hospital	Hamilton
United States	Proacta, Incorporated	San Diego	California

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			Yes
Secondary	Safety of PR-104 as measured by CTCAE v3.0 criteria			Yes
Secondary	Dose-limiting toxicity of PR-104			Yes
Secondary	Pharmacokinetics of PR-104 and its alcohol metabolite in the blood			No
Secondary	Pharmacokinetics of gemcitabine and docetaxel in the presence of PR-104			No
Secondary	Antitumor activity			No