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

NCT00862134 | Terminated Phase 2 Results

• 1 other identifier: PR104-2003
• Study Type: interventional
• Target: 42
• Locations: 3 countries
• Sites: 27

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

Conditions

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

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

  Defined as the number of subjects with complete response (CR) or partial response (PR) using Response Evaluation Criteria in Solid Tumors (RECIST) criteria

  Participants were followed for the duration on study, an average of 4 months

Secondary Outcomes (2)

• Safety and Tolerability: Serious Adverse Events

  30 days following last administration of study treatment

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

  Within 1 year of enrollment

Study Arms (2)

Docetaxel 75 mg/m^2

ACTIVE COMPARATOR

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

Drug: docetaxel

PR104 + 60 mg/m^2 docetaxel

EXPERIMENTAL

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.

Drug: PR104; Drug: docetaxel; Drug: Granulocyte colony-stimulating factor

Interventions

PR104 DRUG

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

PR104 + 60 mg/m^2 docetaxel

docetaxel DRUG

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

Also known as: Taxotere

Docetaxel 75 mg/m^2

Granulocyte colony-stimulating factor 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.

Also known as: G-CSF, GCSF

PR104 + 60 mg/m^2 docetaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Proacta, Incorporated: lead

Study Sites (27)

Sharp Clinical Oncology Research

San Diego, California, 92123, United States

Location

University of Miami/Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Orchard Research, LLC

Skokie, Illinois, 60076, United States

Location

Midwestern Regional Medical Center

Zion, Illinois, 60099, United States

Location

St. Francis Health Services

Beech Grove, Indiana, 46107, United States

Location

McFarland Clinic/William R. Bliss Cancer Center

Ames, Iowa, 50010, United States

Location

Iowa Blood & Cancer Care

Cedar Rapids, Iowa, 52402, United States

Location

Cancer Center of Kansas

Wichita, Kansas, 67214, United States

Location

Montgomery Cancer Center

Mount Sterling, Kentucky, 40353, United States

Location

Baton Rouge General/Penington

Baton Rouge, Louisiana, 70809, United States

Location

Annapolis Oncology Center

Annapolis, Maryland, 21401, United States

Location

Lapidus Cancer Center/Sinai Hospital

Baltimore, Maryland, 21215, United States

Location

Kalamazoo Hematology & Oncology

Kalamazoo, Michigan, 49048, United States

Location

VA Sierra Nevada Health Care System

Reno, Nevada, 89502, United States

Location

VA Medical Center

Durham, North Carolina, United States

Location

Piedmont Hematology Oncology Associates, PLLC

Winston-Salem, North Carolina, 27103, United States

Location

Cincinnati VA Medical Center

Cincinnati, Ohio, 45220, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Location

WJB Dorn VA Medical Center

Columbia, South Carolina, 29209, United States

Location

ACORN

Memphis, Tennessee, 38120, United States

Location

Mary Crowley Medical Research Center

Dallas, Texas, 75246, United States

Location

The Center for Cancer and Blood Disorders

Fort Worth, Texas, 76104, United States

Location

Texas Oncology - Allison Cancer Center

Midland, Texas, 79701, United States

Location

Scott & White Memorial Hospital

Temple, Texas, 76508, United States

Location

McGill University

Montreal, Quebec, H2W 1S6, Canada

Location

Waikato District Health Board

Hamilton, New Zealand

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Docetaxel; Granulocyte Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Director of Clinical Development
• Organization: Proacta, Inc.

clinicalops@proacta.com

858-642-0386

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2009
• First Posted: March 16, 2009
• Study Start: March 1, 2009
• Primary Completion: January 1, 2010
• Study Completion: May 1, 2010
• Last Updated: January 10, 2013
• Results First Posted: January 10, 2013

Record last verified: 2013-01

Locations

CA (1); US (25); NZ (1)