Randomized, Multi-center, Open-label, Study of PR104 Versus PR104/Docetaxel in Non-Small Cell Lung Cancer (NSCLC)
8. januar 2013 opdateret af: Proacta, Incorporated
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.
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
Studieoversigt
Status
Afsluttet
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
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.
Undersøgelsestype
Interventionel
Tilmelding (Faktiske)
42
Fase
- Fase 2
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
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Quebec
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Montreal, Quebec, Canada, H2W 1S6
- McGill University
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California
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San Diego, California, Forenede Stater, 92123
- Sharp Clinical Oncology Research
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Florida
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Miami, Florida, Forenede Stater, 33136
- University of Miami/Sylvester Comprehensive Cancer Center
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Illinois
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Chicago, Illinois, Forenede Stater, 60611
- Northwestern University
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Skokie, Illinois, Forenede Stater, 60076
- Orchard Research, LLC
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Zion, Illinois, Forenede Stater, 60099
- Midwestern Regional Medical Center
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Indiana
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Beech Grove, Indiana, Forenede Stater, 46107
- St. Francis Health Services
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Iowa
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Ames, Iowa, Forenede Stater, 50010
- McFarland Clinic/William R. Bliss Cancer Center
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Cedar Rapids, Iowa, Forenede Stater, 52402
- Iowa Blood & Cancer Care
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Kansas
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Wichita, Kansas, Forenede Stater, 67214
- Cancer Center of Kansas
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Kentucky
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Mt. Sterling, Kentucky, Forenede Stater, 40353
- Montgomery Cancer Center
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Louisiana
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Baton Rouge, Louisiana, Forenede Stater, 70809
- Baton Rouge General/Penington
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Maryland
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Annapolis, Maryland, Forenede Stater, 21401
- Annapolis Oncology Center
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Baltimore, Maryland, Forenede Stater, 21215
- Lapidus Cancer Center/Sinai Hospital
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Michigan
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Kalamazoo, Michigan, Forenede Stater, 49048
- Kalamazoo Hematology & Oncology
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Nevada
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Reno, Nevada, Forenede Stater, 89502
- VA Sierra Nevada Health Care System
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North Carolina
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Durham, North Carolina, Forenede Stater
- VA Medical Center
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Winston-Salem, North Carolina, Forenede Stater, 27103
- Piedmont Hematology Oncology Associates, PLLC
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Ohio
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Cincinnati, Ohio, Forenede Stater, 45220
- Cincinnati VA Medical Center
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Pennsylvania
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Philadelphia, Pennsylvania, Forenede Stater
- University of Pennsylvania
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South Carolina
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Columbia, South Carolina, Forenede Stater, 29209
- WJB Dorn VA Medical Center
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Tennessee
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Memphis, Tennessee, Forenede Stater, 38120
- ACORN
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Texas
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Dallas, Texas, Forenede Stater, 75246
- Mary Crowley Medical Research Center
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Fort Worth, Texas, Forenede Stater, 76104
- The Center for Cancer and Blood Disorders
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Midland, Texas, Forenede Stater, 79701
- Texas Oncology - Allison Cancer Center
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Temple, Texas, Forenede Stater, 76508
- Scott & White Memorial Hospital
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Hamilton, New Zealand
- Waikato District Health Board
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Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
18 år og ældre (Voksen, Ældre voksen)
Tager imod sunde frivillige
Ingen
Køn, der er berettiget til at studere
Alle
Beskrivelse
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
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
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Aktiv komparator: 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)
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75 mg/m^2, IV, every 21 days.
Number of Cycles: until progression or unacceptable toxicity develops.
Andre navne:
60 mg/m^2, IV, every 21 days.
Number of Cycles: until progression or unacceptable toxicity develops.
Andre navne:
|
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Eksperimentel: 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.
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75 mg/m^2, IV, every 21 days.
Number of Cycles: until progression or unacceptable toxicity develops.
Andre navne:
60 mg/m^2, IV, every 21 days.
Number of Cycles: until progression or unacceptable toxicity develops.
Andre navne:
770 mg/m^2, IV, every 21 days.
Number of Cycles: until progression or unacceptable toxicity develops.
Subjects randomized to PR104/docetaxel will receive prophylactic G-CSF per package insert administration recommendations.
Number of Cycles: until progression or unacceptable toxicity develops.
Andre navne:
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Number of Participants That Achieved a Response (Complete or Partial) After Receiving PR104/Docetaxel Versus Docetaxel Alone
Tidsramme: Participants were followed for the duration on study, an average of 4 months
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Defined as the number of subjects with complete response (CR) or partial response (PR) using Response Evaluation Criteria in Solid Tumors (RECIST) criteria
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Participants were followed for the duration on study, an average of 4 months
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Safety and Tolerability: Serious Adverse Events
Tidsramme: 30 days following last administration of study treatment
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The number of participants with at least one Serious Adverse Event was measured.
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30 days following last administration of study treatment
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Positive Aldo-keto Reductase 1C3 (AKR1C3) Expression in Participating Patients
Tidsramme: Within 1 year of enrollment
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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 |
Within 1 year of enrollment
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Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart
1. marts 2009
Primær færdiggørelse (Faktiske)
1. januar 2010
Studieafslutning (Faktiske)
1. maj 2010
Datoer for studieregistrering
Først indsendt
12. marts 2009
Først indsendt, der opfyldte QC-kriterier
13. marts 2009
Først opslået (Skøn)
16. marts 2009
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Skøn)
10. januar 2013
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
8. januar 2013
Sidst verificeret
1. januar 2013
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
- Luftvejssygdomme
- Neoplasmer
- Lungesygdomme
- Neoplasmer efter sted
- Neoplasmer i luftvejene
- Thoracale neoplasmer
- Karcinom, bronkogent
- Bronkiale neoplasmer
- Lungeneoplasmer
- Karcinom, ikke-småcellet lunge
- Lægemidlers fysiologiske virkninger
- Molekylære mekanismer for farmakologisk virkning
- Antineoplastiske midler
- Immunologiske faktorer
- Tubulin modulatorer
- Antimitotiske midler
- Mitose modulatorer
- Adjuvanser, immunologiske
- Docetaxel
- Lenograstim
Andre undersøgelses-id-numre
- PR104-2003
Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .