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

Information source: Proacta, Incorporated
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Non-Small Cell Lung Cancer

Intervention: PR104 (Drug); docetaxel (Drug); docetaxel (Drug); Granulocyte colony-stimulating factor (Drug)

Phase: Phase 2

Status: Terminated

Sponsored by: Proacta, Incorporated

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

Clinical Details

Official title: A Randomized Phase II, Multi-Center, Open-Label Trial of PR104 and Docetaxel in Patients With Advanced Non-Small Cell Lung Cancer

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Number of Participants That Achieved a Response (Complete or Partial) After Receiving PR104/Docetaxel Versus Docetaxel Alone

Secondary outcome:

Safety and Tolerability: Serious Adverse Events

Positive Aldo-keto Reductase 1C3 (AKR1C3) Expression in Participating Patients

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.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Locations and Contacts

Waikato District Health Board, Hamilton, New Zealand

Sharp Clinical Oncology Research, San Diego, California 92123, United States

University of Miami/Sylvester Comprehensive Cancer Center, Miami, Florida 33136, United States

Northwestern University, Chicago, Illinois 60611, United States

Orchard Research, LLC, Skokie, Illinois 60076, United States

Midwestern Regional Medical Center, Zion, Illinois 60099, United States

St. Francis Health Services, Beech Grove, Indiana 46107, United States

McFarland Clinic/William R. Bliss Cancer Center, Ames, Iowa 50010, United States

Iowa Blood & Cancer Care, Cedar Rapids, Iowa 52402, United States

Cancer Center of Kansas, Wichita, Kansas 67214, United States

Montgomery Cancer Center, Mt. Sterling, Kentucky 40353, United States

Baton Rouge General/Penington, Baton Rouge, Louisiana 70809, United States

Annapolis Oncology Center, Annapolis, Maryland 21401, United States

Lapidus Cancer Center/Sinai Hospital, Baltimore, Maryland 21215, United States

Kalamazoo Hematology & Oncology, Kalamazoo, Michigan 49048, United States

VA Sierra Nevada Health Care System, Reno, Nevada 89502, United States

VA Medical Center, Durham, North Carolina, United States

Piedmont Hematology Oncology Associates, PLLC, Winston-Salem, North Carolina 27103, United States

Cincinnati VA Medical Center, Cincinnati, Ohio 45220, United States

University of Pennsylvania, Philadelphia, Pennsylvania, United States

McGill University, Montreal, Quebec H2W 1S6, Canada

WJB Dorn VA Medical Center, Columbia, South Carolina 29209, United States

ACORN, Memphis, Tennessee 38120, United States

Mary Crowley Medical Research Center, Dallas, Texas 75246, United States

The Center for Cancer and Blood Disorders, Fort Worth, Texas 76104, United States

Texas Oncology - Allison Cancer Center, Midland, Texas 79701, United States

Scott & White Memorial Hospital, Temple, Texas 76508, United States

Additional Information

Starting date: March 2009
Last updated: January 8, 2013

Page last updated: August 23, 2015

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