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

8 gennaio 2013 aggiornato da: 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

Panoramica dello studio

Stato

Terminato

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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.

Tipo di studio

Interventistico

Iscrizione (Effettivo)

42

Fase

  • Fase 2

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

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

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

18 anni e precedenti (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

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

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Comparatore attivo: 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)
Droga: docetaxel
75 mg/m^2, IV, every 21 days. Number of Cycles: until progression or unacceptable toxicity develops.
Altri nomi:
  • Taxotere
Droga: docetaxel
60 mg/m^2, IV, every 21 days. Number of Cycles: until progression or unacceptable toxicity develops.
Altri nomi:
  • Taxotere
Sperimentale: 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.
Droga: docetaxel
75 mg/m^2, IV, every 21 days. Number of Cycles: until progression or unacceptable toxicity develops.
Altri nomi:
  • Taxotere
Droga: docetaxel
60 mg/m^2, IV, every 21 days. Number of Cycles: until progression or unacceptable toxicity develops.
Altri nomi:
  • Taxotere
Droga: PR104
770 mg/m^2, IV, every 21 days. Number of Cycles: until progression or unacceptable toxicity develops.
Droga: 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.
Altri nomi:
  • G-CSF
  • GCSF

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Number of Participants That Achieved a Response (Complete or Partial) After Receiving PR104/Docetaxel Versus Docetaxel Alone
Lasso di tempo: 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

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Safety and Tolerability: Serious Adverse Events
Lasso di tempo: 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
Lasso di tempo: 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

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Proacta, Incorporated

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio

1 marzo 2009

Completamento primario (Effettivo)

1 gennaio 2010

Completamento dello studio (Effettivo)

1 maggio 2010

Date di iscrizione allo studio

Primo inviato

12 marzo 2009

Primo inviato che soddisfa i criteri di controllo qualità

13 marzo 2009

Primo Inserito (Stima)

16 marzo 2009

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Stima)

10 gennaio 2013

Ultimo aggiornamento inviato che soddisfa i criteri QC

8 gennaio 2013

Ultimo verificato

1 gennaio 2013

Maggiori informazioni

Termini relativi a questo studio

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • PR104-2003

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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