Non-Small Cell Lung CancerPhase 2NCT00862134
Randomized, Multi-center, Open-label, Study of PR104 Versus PR104/Docetaxel in Non-Small Cell Lung Cancer (NSCLC)
A Phase 2 study testing PR104, docetaxel and Granulocyte colony-stimulating factor in people with Non-Small Cell Lung Cancer, run by Proacta, Incorporated at 27 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Small Cell Lung Cancer
- What is being tested?
- PR104, docetaxel and Granulocyte colony-stimulating factor
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 27 sitesin 3 countries
- Study dates
- Mar 2009to May 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 10Show fewer
- 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)
Who cannot join
- 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
Show all 9Show fewer
- Active Central Nervous System (CNS) metastatic disease requiring intervention
- Less than 4 weeks since major surgery
- Known human immunodeficiency virus (HIV) positivity
Trial locations and contacts
27 sites in 3 countries.
27 sites in 3 countries
United States25 sites
McFarland Clinic/William R. Bliss Cancer Center
Ames, Iowa, 50010
Annapolis Oncology Center
Annapolis, Maryland, 21401
Lapidus Cancer Center/Sinai Hospital
Baltimore, Maryland, 21215
Baton Rouge General/Penington
Baton Rouge, Louisiana, 70809
St. Francis Health Services
Beech Grove, Indiana, 46107
Iowa Blood & Cancer Care
Cedar Rapids, Iowa, 52402
Northwestern University
Chicago, Illinois, 60611
Cincinnati VA Medical Center
Cincinnati, Ohio, 45220
WJB Dorn VA Medical Center
Columbia, South Carolina, 29209
Mary Crowley Medical Research Center
Dallas, Texas, 75246
VA Medical Center
Durham, North Carolina
The Center for Cancer and Blood Disorders
Fort Worth, Texas, 76104
Kalamazoo Hematology & Oncology
Kalamazoo, Michigan, 49048
ACORN
Memphis, Tennessee, 38120
University of Miami/Sylvester Comprehensive Cancer Center
Miami, Florida, 33136
Texas Oncology - Allison Cancer Center
Midland, Texas, 79701
Montgomery Cancer Center
Mount Sterling, Kentucky, 40353
University of Pennsylvania
Philadelphia, Pennsylvania
VA Sierra Nevada Health Care System
Reno, Nevada, 89502
Sharp Clinical Oncology Research
San Diego, California, 92123
Orchard Research, LLC
Skokie, Illinois, 60076
Scott & White Memorial Hospital
Temple, Texas, 76508
Cancer Center of Kansas
Wichita, Kansas, 67214
Piedmont Hematology Oncology Associates, PLLC
Winston-Salem, North Carolina, 27103
Midwestern Regional Medical Center
Zion, Illinois, 60099
About this study
Official title: A Randomized Phase II, Multi-Center, Open-Label Trial of PR104 and Docetaxel in Patients With Advanced Non-Small Cell Lung Cancer
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.
Read more
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
Read the 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
- Being tested
- PR104, docetaxel, Granulocyte colony-stimulating factor
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PR104Drug
770 mg/m^2, IV, every 21 days. Number of Cycles: until progression or unacceptable toxicity develops.
docetaxelDrug
Also called Taxotere
75 mg/m^2, IV, every 21 days. Number of Cycles: until progression or unacceptable toxicity develops.
docetaxelDrug
Also called Taxotere
60 mg/m^2, IV, every 21 days. Number of Cycles: until progression or unacceptable toxicity develops.
Granulocyte colony-stimulating factorDrug
Also called G-CSF, GCSF
Subjects randomized to PR104/docetaxel will receive prophylactic G-CSF per package insert administration recommendations. Number of Cycles: until progression or unacceptable toxicity develops.
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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. Receives: Drug: PR104; Drug: docetaxel; Drug: Granulocyte colony-stimulating factor |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Participants were followed for the duration on study, an average of 4 months
Secondary outcomes (2)
Safety and Tolerability: Serious Adverse Events
The number of participants with at least one Serious Adverse Event was measured.
Measured: 30 days following last administration of study treatment
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
Measured: Within 1 year of enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2009 (estimated)
- Study startMar 2009
- Primary completionJan 2010
- Study completionMay 2010
Why it stopped: Interim analysis indicated low probability of clinically significant result
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Non-Small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Proacta, Incorporated
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00862134
- Sponsor's protocol ID
- PR104-2003
- Status last verified
- Jan 2013
- First submitted
- 12 Mar 2009
- Last updated
- 10 Jan 2013
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Phase II, Multi-Center, Open-Label Trial of PR104 and Docetaxel in Patients With Advanced Non-Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT00862134
- Acronym / sponsor ID
- PR104-2003
- Conditions
- Non-Small Cell Lung Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Interim analysis indicated low probability of clinically significant result
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Proacta, IncorporatedIndustry (pharma, biotech, devices)
- Study start
- Mar 2009
- Primary completion
- Jan 2010 (actual)
- Study completion
- May 2010 (actual)
- First posted
- 16 Mar 2009 (estimated)
- Results
- Posted 10 Jan 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Docetaxel 75 mg/m^2 | Active comparator | Drug: docetaxelSubjects randomized to the docetaxel arm will be administered 75 mg/m^2, IV, every 21 days (an approved dose and schedule) |
| PR104 + 60 mg/m^2 docetaxel | Experimental | Drug: PR104, Drug: docetaxel, Drug: Granulocyte colony-stimulating factorSubjects 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PR104770 mg/m^2, IV, every 21 days. Number of Cycles: until progression or unacceptable toxicity develops. | Drug | PR104 + 60 mg/m^2 docetaxel |
| docetaxelAlso: Taxotere75 mg/m^2, IV, every 21 days. Number of Cycles: until progression or unacceptable toxicity develops. | Drug | Docetaxel 75 mg/m^2 |
| docetaxelAlso: Taxotere60 mg/m^2, IV, every 21 days. Number of Cycles: until progression or unacceptable toxicity develops. | Drug | PR104 + 60 mg/m^2 docetaxel |
| Granulocyte colony-stimulating factorAlso: G-CSF, GCSFSubjects randomized to PR104/docetaxel will receive prophylactic G-CSF per package insert administration recommendations. Number of Cycles: until progression or unacceptable toxicity develops. | Drug | PR104 + 60 mg/m^2 docetaxel |
Primary outcome
Number of Participants That Achieved a Response (Complete or Partial) After Receiving PR104/Docetaxel Versus Docetaxel Alone
Time frame: Participants were followed for the duration on study, an average of 4 months
Defined as the number of subjects with complete response (CR) or partial response (PR) using Response Evaluation Criteria in Solid Tumors (RECIST) criteria
2 secondary outcomes
Safety and Tolerability: Serious Adverse Events
Time frame: 30 days following last administration of study treatment
Positive Aldo-keto Reductase 1C3 (AKR1C3) Expression in Participating Patients
Time frame: Within 1 year of enrollment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
27 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PR104, docetaxel and Granulocyte colony-stimulating factor in people with Non-Small Cell Lung Cancer, run by Proacta, Incorporated at 27 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 10 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in United States, Canada, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Jan 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants That Achieved a Response (Complete or Partial) After Receiving PR104/Docetaxel Versus Docetaxel Alone (time frame: Participants were followed for the duration on study, an average of 4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jan 2013.