Back to resultsRandomized, Multi-center, Open-label, Study of PR104 Versus PR104/Docetaxel in Non-Small Cell Lung Cancer (NSCLC)
Primary Purpose
Non-Small Cell Lung Cancer
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
PR104
docetaxel
docetaxel
Granulocyte colony-stimulating factor
Sponsored by
About this trial
This is an interventional treatment trial for Non-Small Cell Lung Cancer
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
Sites / Locations
- Sharp Clinical Oncology Research
- University of Miami/Sylvester Comprehensive Cancer Center
- Northwestern University
- Orchard Research, LLC
- Midwestern Regional Medical Center
- St. Francis Health Services
- McFarland Clinic/William R. Bliss Cancer Center
- Iowa Blood & Cancer Care
- Cancer Center of Kansas
- Montgomery Cancer Center
- Baton Rouge General/Penington
- Annapolis Oncology Center
- Lapidus Cancer Center/Sinai Hospital
- Kalamazoo Hematology & Oncology
- VA Sierra Nevada Health Care System
- VA Medical Center
- Piedmont Hematology Oncology Associates, PLLC
- Cincinnati VA Medical Center
- University of Pennsylvania
- WJB Dorn VA Medical Center
- ACORN
- Mary Crowley Medical Research Center
- The Center for Cancer and Blood Disorders
- Texas Oncology - Allison Cancer Center
- Scott & White Memorial Hospital
- McGill University
- Waikato District Health Board
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Docetaxel 75 mg/m^2
PR104 + 60 mg/m^2 docetaxel
Arm Description
Subjects randomized to the docetaxel arm will be administered 75 mg/m^2, IV, every 21 days (an approved dose and schedule)
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.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Safety and Tolerability: Serious Adverse Events
The number of participants with at least one Serious Adverse Event was measured.
Positive Aldo-keto Reductase 1C3 (AKR1C3) Expression in Participating Patients
AKR1C3 was evaluated on a semi-quantitative scale, and the percentage of cells staining at each of the following four levels was recorded: 0 (unstained), 1+ (weak staining), 2+ (moderate staining) and 3+ (strong staining).
Patients with a strong staining score (3+) were considered to be AKR1C3 positive
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00862134
Brief Title
Randomized, Multi-center, Open-label, Study of PR104 Versus PR104/Docetaxel in Non-Small Cell Lung Cancer (NSCLC)
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 Type
Interventional
2. Study Status
Record Verification Date
January 2013
Overall Recruitment Status
Terminated
Why Stopped
Interim analysis indicated low probability of clinically significant result
Study Start Date
March 2009 (undefined)
Primary Completion Date
January 2010 (Actual)
Study Completion Date
May 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Proacta, Incorporated
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Small Cell Lung Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
42 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Docetaxel 75 mg/m^2
Arm Type
Active Comparator
Arm Description
Subjects randomized to the docetaxel arm will be administered 75 mg/m^2, IV, every 21 days (an approved dose and schedule)
Arm Title
PR104 + 60 mg/m^2 docetaxel
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
PR104
Intervention Description
770 mg/m^2, IV, every 21 days. Number of Cycles: until progression or unacceptable toxicity develops.
Intervention Type
Drug
Intervention Name(s)
docetaxel
Other Intervention Name(s)
Taxotere
Intervention Description
75 mg/m^2, IV, every 21 days. Number of Cycles: until progression or unacceptable toxicity develops.
Intervention Type
Drug
Intervention Name(s)
docetaxel
Other Intervention Name(s)
Taxotere
Intervention Description
60 mg/m^2, IV, every 21 days. Number of Cycles: until progression or unacceptable toxicity develops.
Intervention Type
Drug
Intervention Name(s)
Granulocyte colony-stimulating factor
Other Intervention Name(s)
G-CSF, GCSF
Intervention Description
Subjects randomized to PR104/docetaxel will receive prophylactic G-CSF per package insert administration recommendations. Number of Cycles: until progression or unacceptable toxicity develops.
Primary Outcome Measure Information:
Title
Number of Participants That Achieved a Response (Complete or Partial) After Receiving PR104/Docetaxel Versus Docetaxel Alone
Description
Defined as the number of subjects with complete response (CR) or partial response (PR) using Response Evaluation Criteria in Solid Tumors (RECIST) criteria
Time Frame
Participants were followed for the duration on study, an average of 4 months
Secondary Outcome Measure Information:
Title
Safety and Tolerability: Serious Adverse Events
Description
The number of participants with at least one Serious Adverse Event was measured.
Time Frame
30 days following last administration of study treatment
Title
Positive Aldo-keto Reductase 1C3 (AKR1C3) Expression in Participating Patients
Description
AKR1C3 was evaluated on a semi-quantitative scale, and the percentage of cells staining at each of the following four levels was recorded: 0 (unstained), 1+ (weak staining), 2+ (moderate staining) and 3+ (strong staining).
Patients with a strong staining score (3+) were considered to be AKR1C3 positive
Time Frame
Within 1 year of enrollment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
Sharp Clinical Oncology Research
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
University of Miami/Sylvester Comprehensive Cancer Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Orchard Research, LLC
City
Skokie
State/Province
Illinois
ZIP/Postal Code
60076
Country
United States
Facility Name
Midwestern Regional Medical Center
City
Zion
State/Province
Illinois
ZIP/Postal Code
60099
Country
United States
Facility Name
St. Francis Health Services
City
Beech Grove
State/Province
Indiana
ZIP/Postal Code
46107
Country
United States
Facility Name
McFarland Clinic/William R. Bliss Cancer Center
City
Ames
State/Province
Iowa
ZIP/Postal Code
50010
Country
United States
Facility Name
Iowa Blood & Cancer Care
City
Cedar Rapids
State/Province
Iowa
ZIP/Postal Code
52402
Country
United States
Facility Name
Cancer Center of Kansas
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67214
Country
United States
Facility Name
Montgomery Cancer Center
City
Mt. Sterling
State/Province
Kentucky
ZIP/Postal Code
40353
Country
United States
Facility Name
Baton Rouge General/Penington
City
Baton Rouge
State/Province
Louisiana
ZIP/Postal Code
70809
Country
United States
Facility Name
Annapolis Oncology Center
City
Annapolis
State/Province
Maryland
ZIP/Postal Code
21401
Country
United States
Facility Name
Lapidus Cancer Center/Sinai Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21215
Country
United States
Facility Name
Kalamazoo Hematology & Oncology
City
Kalamazoo
State/Province
Michigan
ZIP/Postal Code
49048
Country
United States
Facility Name
VA Sierra Nevada Health Care System
City
Reno
State/Province
Nevada
ZIP/Postal Code
89502
Country
United States
Facility Name
VA Medical Center
City
Durham
State/Province
North Carolina
Country
United States
Facility Name
Piedmont Hematology Oncology Associates, PLLC
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27103
Country
United States
Facility Name
Cincinnati VA Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45220
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
Country
United States
Facility Name
WJB Dorn VA Medical Center
City
Columbia
State/Province
South Carolina
ZIP/Postal Code
29209
Country
United States
Facility Name
ACORN
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38120
Country
United States
Facility Name
Mary Crowley Medical Research Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
The Center for Cancer and Blood Disorders
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Facility Name
Texas Oncology - Allison Cancer Center
City
Midland
State/Province
Texas
ZIP/Postal Code
79701
Country
United States
Facility Name
Scott & White Memorial Hospital
City
Temple
State/Province
Texas
ZIP/Postal Code
76508
Country
United States
Facility Name
McGill University
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2W 1S6
Country
Canada
Facility Name
Waikato District Health Board
City
Hamilton
Country
New Zealand
12. IPD Sharing Statement
Learn more about this trial
Randomized, Multi-center, Open-label, Study of PR104 Versus PR104/Docetaxel in Non-Small Cell Lung Cancer (NSCLC)
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