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

8. januar 2013 oppdatert av: 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

Studieoversikt

Status

Avsluttet

Forhold

Intervensjon / Behandling

Detaljert 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.

Studietype

Intervensjonell

Registrering (Faktiske)

42

Fase

  • Fase 2

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H2W 1S6
        • McGill University
  • Forente stater
    • California
      • San Diego, California, Forente stater, 92123
        • Sharp Clinical Oncology Research
    • Florida
      • Miami, Florida, Forente stater, 33136
        • University of Miami/Sylvester Comprehensive Cancer Center
    • Illinois
      • Chicago, Illinois, Forente stater, 60611
        • Northwestern University
      • Skokie, Illinois, Forente stater, 60076
        • Orchard Research, LLC
      • Zion, Illinois, Forente stater, 60099
        • Midwestern Regional Medical Center
    • Indiana
      • Beech Grove, Indiana, Forente stater, 46107
        • St. Francis Health Services
    • Iowa
      • Ames, Iowa, Forente stater, 50010
        • McFarland Clinic/William R. Bliss Cancer Center
      • Cedar Rapids, Iowa, Forente stater, 52402
        • Iowa Blood & Cancer Care
    • Kansas
      • Wichita, Kansas, Forente stater, 67214
        • Cancer Center of Kansas
    • Kentucky
      • Mt. Sterling, Kentucky, Forente stater, 40353
        • Montgomery Cancer Center
    • Louisiana
      • Baton Rouge, Louisiana, Forente stater, 70809
        • Baton Rouge General/Penington
    • Maryland
      • Annapolis, Maryland, Forente stater, 21401
        • Annapolis Oncology Center
      • Baltimore, Maryland, Forente stater, 21215
        • Lapidus Cancer Center/Sinai Hospital
    • Michigan
      • Kalamazoo, Michigan, Forente stater, 49048
        • Kalamazoo Hematology & Oncology
    • Nevada
      • Reno, Nevada, Forente stater, 89502
        • VA Sierra Nevada Health Care System
    • North Carolina
      • Durham, North Carolina, Forente stater
        • VA Medical Center
      • Winston-Salem, North Carolina, Forente stater, 27103
        • Piedmont Hematology Oncology Associates, PLLC
    • Ohio
      • Cincinnati, Ohio, Forente stater, 45220
        • Cincinnati VA Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, Forente stater
        • University of Pennsylvania
    • South Carolina
      • Columbia, South Carolina, Forente stater, 29209
        • WJB Dorn VA Medical Center
    • Tennessee
      • Memphis, Tennessee, Forente stater, 38120
        • ACORN
    • Texas
      • Dallas, Texas, Forente stater, 75246
        • Mary Crowley Medical Research Center
      • Fort Worth, Texas, Forente stater, 76104
        • The Center for Cancer and Blood Disorders
      • Midland, Texas, Forente stater, 79701
        • Texas Oncology - Allison Cancer Center
      • Temple, Texas, Forente stater, 76508
        • Scott & White Memorial Hospital
  • New Zealand
      • Hamilton, New Zealand
        • Waikato District Health Board

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

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

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
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)
Legemiddel: docetaxel
75 mg/m^2, IV, every 21 days. Number of Cycles: until progression or unacceptable toxicity develops.
Andre navn:
  • Taxotere
Legemiddel: docetaxel
60 mg/m^2, IV, every 21 days. Number of Cycles: until progression or unacceptable toxicity develops.
Andre navn:
  • Taxotere
Eksperimentell: 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.
Legemiddel: docetaxel
75 mg/m^2, IV, every 21 days. Number of Cycles: until progression or unacceptable toxicity develops.
Andre navn:
  • Taxotere
Legemiddel: docetaxel
60 mg/m^2, IV, every 21 days. Number of Cycles: until progression or unacceptable toxicity develops.
Andre navn:
  • Taxotere
Legemiddel: PR104
770 mg/m^2, IV, every 21 days. Number of Cycles: until progression or unacceptable toxicity develops.
Legemiddel: 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.
Andre navn:
  • G-CSF
  • GCSF

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
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
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

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Safety and Tolerability: Serious Adverse Events
Tidsramme: 30 days following last administration of study treatment
The number of participants with at least one Serious Adverse Event was measured.
30 days following last administration of study treatment
Positive Aldo-keto Reductase 1C3 (AKR1C3) Expression in Participating Patients
Tidsramme: Within 1 year of enrollment

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

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Proacta, Incorporated

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart

1. mars 2009

Primær fullføring (Faktiske)

1. januar 2010

Studiet fullført (Faktiske)

1. mai 2010

Datoer for studieregistrering

Først innsendt

12. mars 2009

Først innsendt som oppfylte QC-kriteriene

13. mars 2009

Først lagt ut (Anslag)

16. mars 2009

Oppdateringer av studieposter

Sist oppdatering lagt ut (Anslag)

10. januar 2013

Siste oppdatering sendt inn som oppfylte QC-kriteriene

8. januar 2013

Sist bekreftet

1. januar 2013

Mer informasjon

Begreper knyttet til denne studien

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • PR104-2003

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