Randomized, Multi-center, Open-label, Study of PR104 Versus PR104/Docetaxel in Non-Small Cell Lung Cancer (NSCLC)
2013年1月8日 更新者：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
調査の概要
詳細な説明
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.
研究の種類
介入
入学 (実際)
42
段階
- フェーズ2
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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California
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San Diego、California、アメリカ、92123
- Sharp Clinical Oncology Research
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Florida
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Miami、Florida、アメリカ、33136
- University of Miami/Sylvester Comprehensive Cancer Center
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Illinois
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Chicago、Illinois、アメリカ、60611
- Northwestern University
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Skokie、Illinois、アメリカ、60076
- Orchard Research, LLC
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Zion、Illinois、アメリカ、60099
- Midwestern Regional Medical Center
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Indiana
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Beech Grove、Indiana、アメリカ、46107
- St. Francis Health Services
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Iowa
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Ames、Iowa、アメリカ、50010
- McFarland Clinic/William R. Bliss Cancer Center
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Cedar Rapids、Iowa、アメリカ、52402
- Iowa Blood & Cancer Care
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Kansas
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Wichita、Kansas、アメリカ、67214
- Cancer Center of Kansas
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Kentucky
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Mt. Sterling、Kentucky、アメリカ、40353
- Montgomery Cancer Center
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Louisiana
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Baton Rouge、Louisiana、アメリカ、70809
- Baton Rouge General/Penington
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Maryland
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Annapolis、Maryland、アメリカ、21401
- Annapolis Oncology Center
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Baltimore、Maryland、アメリカ、21215
- Lapidus Cancer Center/Sinai Hospital
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Michigan
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Kalamazoo、Michigan、アメリカ、49048
- Kalamazoo Hematology & Oncology
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Nevada
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Reno、Nevada、アメリカ、89502
- VA Sierra Nevada Health Care System
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North Carolina
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Durham、North Carolina、アメリカ
- VA Medical Center
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Winston-Salem、North Carolina、アメリカ、27103
- Piedmont Hematology Oncology Associates, PLLC
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Ohio
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Cincinnati、Ohio、アメリカ、45220
- Cincinnati VA Medical Center
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Pennsylvania
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Philadelphia、Pennsylvania、アメリカ
- University of Pennsylvania
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South Carolina
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Columbia、South Carolina、アメリカ、29209
- WJB Dorn VA Medical Center
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Tennessee
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Memphis、Tennessee、アメリカ、38120
- ACORN
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Texas
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Dallas、Texas、アメリカ、75246
- Mary Crowley Medical Research Center
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Fort Worth、Texas、アメリカ、76104
- The Center for Cancer and Blood Disorders
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Midland、Texas、アメリカ、79701
- Texas Oncology - Allison Cancer Center
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Temple、Texas、アメリカ、76508
- Scott & White Memorial Hospital
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Quebec
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Montreal、Quebec、カナダ、H2W 1S6
- McGill University
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Hamilton、ニュージーランド
- Waikato District Health Board
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年歳以上 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
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
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
アクティブコンパレータ：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)
|
75 mg/m^2, IV, every 21 days.
Number of Cycles: until progression or unacceptable toxicity develops.
他の名前：
60 mg/m^2, IV, every 21 days.
Number of Cycles: until progression or unacceptable toxicity develops.
他の名前：
|
|
実験的：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.
|
75 mg/m^2, IV, every 21 days.
Number of Cycles: until progression or unacceptable toxicity develops.
他の名前：
60 mg/m^2, IV, every 21 days.
Number of Cycles: until progression or unacceptable toxicity develops.
他の名前：
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.
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Number of Participants That Achieved a Response (Complete or Partial) After Receiving PR104/Docetaxel Versus Docetaxel Alone
時間枠：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
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Safety and Tolerability: Serious Adverse Events
時間枠：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
|
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Positive Aldo-keto Reductase 1C3 (AKR1C3) Expression in Participating Patients
時間枠：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
|
協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始
2009年3月1日
一次修了 (実際)
2010年1月1日
研究の完了 (実際)
2010年5月1日
試験登録日
最初に提出
2009年3月12日
QC基準を満たした最初の提出物
2009年3月13日
最初の投稿 (見積もり)
2009年3月16日
学習記録の更新
投稿された最後の更新 (見積もり)
2013年1月10日
QC基準を満たした最後の更新が送信されました
2013年1月8日
最終確認日
2013年1月1日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
非小細胞肺がんの臨床試験
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Adelphi Values LLCBlueprint Medicines Corporation完了肥満細胞性白血病 (MCL) | 攻撃的な全身性肥満細胞症 (ASM) | SM w Assoc Clonal Hema Non-mast Cell Lineage Disease (SM-AHNMD) | くすぶり全身性肥満細胞症 (SSM) | 無痛性全身性肥満細胞症 (ISM) ISM サブグループが完全に募集されましたアメリカ