Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00862134




Registration number
NCT00862134
Ethics application status
Date submitted
12/03/2009
Date registered
16/03/2009
Date last updated
10/01/2013

Titles & IDs
Public title
Randomized, Multi-center, Open-label, Study of PR104 Versus PR104/Docetaxel in Non-Small Cell Lung Cancer (NSCLC)
Scientific title
A Randomized Phase II, Multi-Center, Open-Label Trial of PR104 and Docetaxel in Patients With Advanced Non-Small Cell Lung Cancer
Secondary ID [1] 0 0
PR104-2003
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - PR104
Treatment: Drugs - docetaxel
Treatment: Drugs - docetaxel
Treatment: Drugs - Granulocyte colony-stimulating factor

Active Comparator: 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)

Experimental: 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.


Treatment: Drugs: PR104
770 mg/m^2, IV, every 21 days. Number of Cycles: until progression or unacceptable toxicity develops.

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

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

Treatment: Drugs: 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 code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants That Achieved a Response (Complete or Partial) After Receiving PR104/Docetaxel Versus Docetaxel Alone
Timepoint [1] 0 0
Participants were followed for the duration on study, an average of 4 months
Secondary outcome [1] 0 0
Safety and Tolerability: Serious Adverse Events
Timepoint [1] 0 0
30 days following last administration of study treatment
Secondary outcome [2] 0 0
Positive Aldo-keto Reductase 1C3 (AKR1C3) Expression in Participating Patients
Timepoint [2] 0 0
Within 1 year of enrollment

Eligibility
Key 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)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/03/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/05/2010
Sample size
Target
Accrual to date
Final
42
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Indiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Iowa
Country [6] 0 0
United States of America
State/province [6] 0 0
Kansas
Country [7] 0 0
United States of America
State/province [7] 0 0
Kentucky
Country [8] 0 0
United States of America
State/province [8] 0 0
Louisiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Maryland
Country [10] 0 0
United States of America
State/province [10] 0 0
Michigan
Country [11] 0 0
United States of America
State/province [11] 0 0
Nevada
Country [12] 0 0
United States of America
State/province [12] 0 0
North Carolina
Country [13] 0 0
United States of America
State/province [13] 0 0
Ohio
Country [14] 0 0
United States of America
State/province [14] 0 0
Pennsylvania
Country [15] 0 0
United States of America
State/province [15] 0 0
South Carolina
Country [16] 0 0
United States of America
State/province [16] 0 0
Tennessee
Country [17] 0 0
United States of America
State/province [17] 0 0
Texas
Country [18] 0 0
Canada
State/province [18] 0 0
Quebec
Country [19] 0 0
New Zealand
State/province [19] 0 0
Hamilton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Proacta, Incorporated
Address
Country

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/ct2/show/NCT00862134
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00862134