Randomized, Multi-center, Open-label, Study of PR104 Versus PR104/Docetaxel in Non-Small Cell Lung Cancer (NSCLC)
8. Januar 2013 aktualisiert von: 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
Studienübersicht
Status
Beendet
Bedingungen
Intervention / Behandlung
Detaillierte Beschreibung
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.
Studientyp
Interventionell
Einschreibung (Tatsächlich)
42
Phase
- Phase 2
Kontakte und Standorte
Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.
Studienorte
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Quebec
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Montreal, Quebec, Kanada, H2W 1S6
- McGill University
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Hamilton, Neuseeland
- Waikato District Health Board
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California
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San Diego, California, Vereinigte Staaten, 92123
- Sharp Clinical Oncology Research
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Florida
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Miami, Florida, Vereinigte Staaten, 33136
- University of Miami/Sylvester Comprehensive Cancer Center
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Illinois
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Chicago, Illinois, Vereinigte Staaten, 60611
- Northwestern University
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Skokie, Illinois, Vereinigte Staaten, 60076
- Orchard Research, LLC
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Zion, Illinois, Vereinigte Staaten, 60099
- Midwestern Regional Medical Center
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Indiana
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Beech Grove, Indiana, Vereinigte Staaten, 46107
- St. Francis Health Services
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Iowa
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Ames, Iowa, Vereinigte Staaten, 50010
- McFarland Clinic/William R. Bliss Cancer Center
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Cedar Rapids, Iowa, Vereinigte Staaten, 52402
- Iowa Blood & Cancer Care
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Kansas
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Wichita, Kansas, Vereinigte Staaten, 67214
- Cancer Center of Kansas
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Kentucky
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Mt. Sterling, Kentucky, Vereinigte Staaten, 40353
- Montgomery Cancer Center
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Louisiana
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Baton Rouge, Louisiana, Vereinigte Staaten, 70809
- Baton Rouge General/Penington
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Maryland
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Annapolis, Maryland, Vereinigte Staaten, 21401
- Annapolis Oncology Center
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Baltimore, Maryland, Vereinigte Staaten, 21215
- Lapidus Cancer Center/Sinai Hospital
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Michigan
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Kalamazoo, Michigan, Vereinigte Staaten, 49048
- Kalamazoo Hematology & Oncology
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Nevada
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Reno, Nevada, Vereinigte Staaten, 89502
- VA Sierra Nevada Health Care System
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North Carolina
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Durham, North Carolina, Vereinigte Staaten
- VA Medical Center
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Winston-Salem, North Carolina, Vereinigte Staaten, 27103
- Piedmont Hematology Oncology Associates, PLLC
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Ohio
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Cincinnati, Ohio, Vereinigte Staaten, 45220
- Cincinnati VA Medical Center
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Pennsylvania
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Philadelphia, Pennsylvania, Vereinigte Staaten
- University of Pennsylvania
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South Carolina
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Columbia, South Carolina, Vereinigte Staaten, 29209
- WJB Dorn VA Medical Center
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Tennessee
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Memphis, Tennessee, Vereinigte Staaten, 38120
- ACORN
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Texas
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Dallas, Texas, Vereinigte Staaten, 75246
- Mary Crowley Medical Research Center
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Fort Worth, Texas, Vereinigte Staaten, 76104
- The Center for Cancer and Blood Disorders
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Midland, Texas, Vereinigte Staaten, 79701
- Texas Oncology - Allison Cancer Center
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Temple, Texas, Vereinigte Staaten, 76508
- Scott & White Memorial Hospital
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Teilnahmekriterien
Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.
Zulassungskriterien
Studienberechtigtes Alter
18 Jahre und älter (Erwachsene, Älterer Erwachsener)
Akzeptiert gesunde Freiwillige
Nein
Studienberechtigte Geschlechter
Alle
Beschreibung
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
Studienplan
Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Zufällig
- Interventionsmodell: Parallele Zuordnung
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
|---|---|
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Aktiver 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.
Andere Namen:
60 mg/m^2, IV, every 21 days.
Number of Cycles: until progression or unacceptable toxicity develops.
Andere Namen:
|
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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.
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75 mg/m^2, IV, every 21 days.
Number of Cycles: until progression or unacceptable toxicity develops.
Andere Namen:
60 mg/m^2, IV, every 21 days.
Number of Cycles: until progression or unacceptable toxicity develops.
Andere Namen:
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.
Andere Namen:
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Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
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Number of Participants That Achieved a Response (Complete or Partial) After Receiving PR104/Docetaxel Versus Docetaxel Alone
Zeitfenster: 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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Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
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Safety and Tolerability: Serious Adverse Events
Zeitfenster: 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
Zeitfenster: 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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Mitarbeiter und Ermittler
Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.
Sponsor
Studienaufzeichnungsdaten
Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.
Haupttermine studieren
Studienbeginn
1. März 2009
Primärer Abschluss (Tatsächlich)
1. Januar 2010
Studienabschluss (Tatsächlich)
1. Mai 2010
Studienanmeldedaten
Zuerst eingereicht
12. März 2009
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
13. März 2009
Zuerst gepostet (Schätzen)
16. März 2009
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Schätzen)
10. Januar 2013
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
8. Januar 2013
Zuletzt verifiziert
1. Januar 2013
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Zusätzliche relevante MeSH-Bedingungen
- Erkrankungen der Atemwege
- Neubildungen
- Lungenkrankheit
- Neubildungen nach Standort
- Neubildungen der Atemwege
- Thoraxneoplasmen
- Karzinom, bronchogen
- Bronchiale Neubildungen
- Lungentumoren
- Karzinom, nicht-kleinzellige Lunge
- Physiologische Wirkungen von Arzneimitteln
- Molekulare Mechanismen der pharmakologischen Wirkung
- Antineoplastische Mittel
- Immunologische Faktoren
- Tubulin-Modulatoren
- Antimitotische Mittel
- Mitose-Modulatoren
- Adjuvantien, Immunologische
- Docetaxel
- Lenograstim
Andere Studien-ID-Nummern
- PR104-2003
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