Randomized, Multi-center, Open-label, Study of PR104 Versus PR104/Docetaxel in Non-Small Cell Lung Cancer (NSCLC)

NCT ID: NCT00862134

Last Updated: 2013-01-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-03-31
• Study Completion Date: 2010-05-31

Brief Summary

The current understanding of PR104 justifies the evaluation of PR104 with docetaxel in subjects with Non Small Cell Lung Cancer (NSCLC). These include:

• Aldo-keto reductase 1C3 (AKR1C3). NSCLC has been shown to express high levels of AKR1C3 in about one half of tumors tested. Subjects with high levels of AKR1C3 should have increased activation of PR104 within their tumor.
• Hypoxia. NSCLC has been demonstrated to be a tumor with hypoxia based on both direct tumor measurements (oxygen electrodes) and hypoxic positron emission tomography (PET) imaging. Tumor hypoxia in NSCLC should be sufficient to activate PR104 to its active metabolites PR104H and PR104M.
• Preclinical data. The use of docetaxel and PR104 alone and in combination in preclinical models demonstrates activity of PR104 as a single agent and supraadditive activity when PR104 and docetaxel are used in combination.
• Manageable toxicity. PR104 and docetaxel with Granulocyte Colony-stimulating Factor (G-CSF) have been combined in a prior phase I study. A Maximum Tolerated Dose (MTD) has been identified and the major toxicities of this combination are understood.

The current study will provide an estimate of the activity of PR104 in subjects with NSCLC. This information will prove valuable in defining the future clinical development of PR104, and in determining if PR104 has sufficient activity in NSCLC to warrant a larger phase III registration study in this indication.

Primary objectives

• Estimate the response rate (RR) of PR104/docetaxel

Secondary objectives

• Evaluate survival
• Evaluate progression free survival (PFS)
• Evaluate time to progression (TTP)
• Evaluate safety
• Evaluate the pharmacokinetics of PR104 and its metabolites
• Evaluate the pharmacokinetics of docetaxel
• Evaluate the tumor hypoxia using 18F-fluoromisonidazole (18F-MISO) PET imaging
• Collect diagnostic biopsy samples for the determination of AKR1C3
• Collect plasma samples for assessment of potential biomarkers of tumor hypoxia

Detailed Description

A randomized phase II, multi-center, open-label, study of docetaxel versus docetaxel/PR104.

Following informed consent, subjects will undergo baseline evaluation with history, physical exams, blood work and disease assessment. Selected subjects will undergo PET imaging with F18 fluoromisonidazole (F18-FMISO) and Fludeoxyglucose (FDG) for assessment of hypoxia and glucose metabolism, and pharmacokinetics of PR104.

Subjects will be randomized between arm 1 consisting of docetaxel, 75 mg/m^2, administered intravenously (IV), every 21 days (an approved dose and schedule) and arm 2 consisting of docetaxel, 60 mg/m^2 with PR104 at 770 mg/m^2, IV, every 21 days. Subjects randomized to PR104/docetaxel will receive prophylactic G-CSF. One cycle will be 21 days in duration. Subjects will be evaluated weekly. A disease assessment will be performed every six weeks. Subjects with progression will be removed from study. Subjects with a response or stable disease may continue on study if this is considered beneficial by their physician.

Conditions

Non-Small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Docetaxel 75 mg/m^2

Subjects randomized to the docetaxel arm will be administered 75 mg/m\^2, IV, every 21 days (an approved dose and schedule)

Group Type: ACTIVE_COMPARATOR

docetaxel

Intervention Type: DRUG

75 mg/m\^2, IV, every 21 days. Number of Cycles: until progression or unacceptable toxicity develops.

PR104 + 60 mg/m^2 docetaxel

Subjects randomized to the PR104/docetaxel arm will be administered 60 mg/m\^2 docetaxel, IV, every 21 days plus 770 mg/m\^2 PR104, IV, every 21 days and prophylactic G-CSF.

Group Type: EXPERIMENTAL

PR104

Intervention Type: DRUG

770 mg/m\^2, IV, every 21 days. Number of Cycles: until progression or unacceptable toxicity develops.

docetaxel

Intervention Type: DRUG

60 mg/m\^2, IV, every 21 days. Number of Cycles: until progression or unacceptable toxicity develops.

Granulocyte colony-stimulating factor

Intervention Type: DRUG

Subjects randomized to PR104/docetaxel will receive prophylactic G-CSF per package insert administration recommendations. Number of Cycles: until progression or unacceptable toxicity develops.

Interventions

PR104

770 mg/m\^2, IV, every 21 days. Number of Cycles: until progression or unacceptable toxicity develops.

Intervention Type: DRUG

docetaxel

75 mg/m\^2, IV, every 21 days. Number of Cycles: until progression or unacceptable toxicity develops.

Intervention Type: DRUG

docetaxel

60 mg/m\^2, IV, every 21 days. Number of Cycles: until progression or unacceptable toxicity develops.

Intervention Type: DRUG

Granulocyte colony-stimulating factor

Subjects randomized to PR104/docetaxel will receive prophylactic G-CSF per package insert administration recommendations. Number of Cycles: until progression or unacceptable toxicity develops.

Intervention Type: DRUG

Other Intervention Names

Taxotere; Taxotere; G-CSF; GCSF

Eligibility Criteria

Inclusion Criteria

• Subjects with locally advanced or metastatic NSCLC (stage IIIb/IV) who have relapsed following adjuvant or first line therapy with a platinum containing regimen, and are appropriate candidates for treatment with single agent docetaxel
• Confirmed NSCLC by prior pathological analysis (tissue aspirate or biopsy)
• At least 21 days from prior chemotherapy
• At least 30 days from prior irradiation therapy
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Life expectancy of 12 weeks or more
• Adequate hematologic function [Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L; platelet count ≥100x10^9/L; hemoglobin ≥8.5 g /dL maintained in the absence of red blood cell transfusions; and prothrombin time international normalized ratio ≤1.7; or prothrombin time ≤2 seconds above control)
• Adequate hepatic function (albumin ≥2.8 g/dL; total bilirubin ≤2 mg/dL [51.3 μmol/L]; and alanine aminotransferase and aspartate aminotransferase ≤1.5 times the upper limit of the normal range)
• Adequate renal function (serum creatinine ≤2.0 times the upper limit of the normal range or creatinine clearance ≥60 mL/min).
• At least one untreated target lesion that could be measured in one dimension, according to the Response Evaluation Criteria in Solid Tumors (RECIST)

Exclusion Criteria

• Previous treatment with docetaxel (prior treatment with paclitaxel permitted)
• Receipt of more than one prior systemic chemotherapy regimen
• Active concomitant malignancy likely to effect any of the primary or secondary outcome measures in the current study
• Women who are pregnant, breast-feeding or planning to become pregnant during the study
• Men or women of reproductive-potential who are unwilling to use an effective method of contraception during the study and for 30 days following the last dose
• Evidence of a significant medical disorder or laboratory finding that, in the opinion of the Investigator, compromises the subject's safety during study participation
• Active Central Nervous System (CNS) metastatic disease requiring intervention
• Less than 4 weeks since major surgery
• Known human immunodeficiency virus (HIV) positivity

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Proacta, Incorporated

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Sharp Clinical Oncology Research

San Diego, California, United States

University of Miami/Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Northwestern University

Chicago, Illinois, United States

Orchard Research, LLC

Skokie, Illinois, United States

Midwestern Regional Medical Center

Zion, Illinois, United States

St. Francis Health Services

Beech Grove, Indiana, United States

McFarland Clinic/William R. Bliss Cancer Center

Ames, Iowa, United States

Iowa Blood & Cancer Care

Cedar Rapids, Iowa, United States

Cancer Center of Kansas

Wichita, Kansas, United States

Montgomery Cancer Center

Mount Sterling, Kentucky, United States

Baton Rouge General/Penington

Baton Rouge, Louisiana, United States

Annapolis Oncology Center

Annapolis, Maryland, United States

Lapidus Cancer Center/Sinai Hospital

Baltimore, Maryland, United States

Kalamazoo Hematology & Oncology

Kalamazoo, Michigan, United States

VA Sierra Nevada Health Care System

Reno, Nevada, United States

VA Medical Center

Durham, North Carolina, United States

Piedmont Hematology Oncology Associates, PLLC

Winston-Salem, North Carolina, United States

Cincinnati VA Medical Center

Cincinnati, Ohio, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

WJB Dorn VA Medical Center

Columbia, South Carolina, United States

ACORN

Memphis, Tennessee, United States

Mary Crowley Medical Research Center

Dallas, Texas, United States

The Center for Cancer and Blood Disorders

Fort Worth, Texas, United States

Texas Oncology - Allison Cancer Center

Midland, Texas, United States

Scott & White Memorial Hospital

Temple, Texas, United States

McGill University

Montreal, Quebec, Canada

Waikato District Health Board

Hamilton, , New Zealand

Countries

United States; Canada; New Zealand

Other Identifiers

PR104-2003

Identifier Type: -

Identifier Source: org_study_id

NCT00840021

Identifier Type: -

Identifier Source: nct_alias