Radiation Therapy and Temozolomide Followed by Temozolomide Plus Sorafenib for Glioblastoma Multiforme
A Phase II Trial of Concurrent Radiation Therapy and Temozolomide Followed by Temozolomide Plus Sorafenib in the First-Line Treatment of Patients With Glioblastoma Multiforme
The mechanism of action of sorafenib makes it an interesting drug to investigate in the treatment of patients with glioblastoma multiforme. Efficacy of agents with anti-angiogenic activity has already been demonstrated and the PDGF receptor target may also be pertinent in glioblastoma. The combination of temozolomide plus sorafenib has been investigated previously in the treatment of patients with advanced melanoma. The combination was generally well tolerated; in previously untreated patients, a standard dose of sorafenib (400mg PO bid) was administered with temozolomide 150mg/m2 PO daily for 5 days, repeated every 28 days (23).
In this multicenter phase II study, patients with newly diagnosed glioblastoma will receive standard treatment, including initial debulking surgical resection (if feasible) followed by high-dose radiation therapy with concurrent temozolomide. After completion of radiation therapy, patients will continue treatment with temozolomide (150mg/m2 days 1-5) and sorafenib (400mg PO bid daily), repeated at 28-day intervals for 6 cycles.
調査の概要
詳細な説明
All patients entering this study will initially undergo combined modality treatment with concurrent radiation therapy + temozolomide. Four weeks after completing radiation therapy, patients will begin 6 months of follow-up treatment with oral temozolomide plus sorafenib.
Combined Modality Therapy - Radiation Therapy Radiotherapy must begin within ≤ 6 weeks of surgery. One treatment of 2.0Gy will be given daily 5 days per week for a total of 60.0Gy over 6 weeks. Temozolomide 75mg/m2 PO will be given daily, beginning on the first day of radiation therapy and continuing through the last day of radiation therapy.
After completion of combined modality therapy, patients will have 4 weeks without any therapy.
Systemic Therapy Beginning 4 weeks after the completion of radiation therapy, patients will receive 6 months of treatment with temozolomide and sorafenib. Temozolomide 150mg/m2 orally will be administered days 1-5, and repeated every 28 days for 6 courses. Sorafenib 400mg PO bid will be administered on days 1-28, repeated for 6 courses concurrently with temozolomide
研究の種類
入学 (実際)
段階
- フェーズ2
連絡先と場所
研究場所
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Florida
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Fort Myers、Florida、アメリカ、33901
- Florida Cancer Specialists
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Georgia
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Gainesville、Georgia、アメリカ、30501
- Northeast Georgia Medical Center
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Maryland
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Bethesda、Maryland、アメリカ、20817
- Center for Cancer and Blood Disorders
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Michigan
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Grand Rapids、Michigan、アメリカ、49503
- Grand Rapids Clinical Oncology Program
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Nebraska
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Omaha、Nebraska、アメリカ、68114
- Methodist Cancer Center
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Ohio
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Cincinnati、Ohio、アメリカ、45242
- Oncology Hematology Care
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South Carolina
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Spartanburg、South Carolina、アメリカ、29303
- Spartanburg Regional Medical Center
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Tennessee
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Nashville、Tennessee、アメリカ、37203
- Tennessee Oncology
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Texas
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San Antonio、Texas、アメリカ、78258
- South Texas Oncology And Hematology
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Virginia
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Richmond、Virginia、アメリカ、23235
- Virginia Cancer Institute
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- Histologically confirmed intracranial glioblastoma multiforme (WHO grade 4).
- Patients who have had partial or complete surgical debulking are eligible, as are those with inoperable glioblastoma.
- No previous treatment for glioblastoma except for previous surgical debulking (i.e. no previous radiotherapy, local chemotherapy, or systemic therapy).
- ECOG performance status 0 or 1 (See Appendix C)
- Age ≥ 18 years
- Adequate bone marrow function: hemoglobin ≥ 9.0g/dL; ANC ≥ 1500/μL; platelet count ≥ 100,000/μL.
Adequate liver function
- Total bilirubin ≤ 1.5 x ULN
- ALT and AST ≤ 2.5 x ULN
- Serum creatinine < 1.5 x ULN
- Women of child-bearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment. Women must agree to not breast feed while receiving study treatment.
- Women of child-bearing potential and men must agree to use adequate contraception (barrier method of birth control) while receiving study treatment. Women should use adequate birth control for at least 3 months after the last administration of sorafenib.
- INR < 1.5 or PT/PTT within normal limits in patients not receiving anticoagulation. However, patients receiving anticoagulation treatment with an agent such as warfarin or heparin are also eligible. For patients on warfarin, the INR should be measured prior to initiation of sorafenib and monitored at least weekly, or as defined by the local standard of care, until INR is stable.
- Patients must have the ability to understand and the willingness to sign written informed consent. A signed informed consent must be obtained prior to any study-specific procedures.
Exclusion Criteria:
- Patients must have the ability to swallow whole pills.
- Active cardiac disease: congestive heart failure > class 2 NYHA (Appendix D); unstable angina or new onset angina within the last 3 months; myocardial infarction within the last 6 months.
- Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
- Uncontrolled hypertension defined as systolic blood pressure > 150mm Hg or diastolic pressure > 90mm Hg, despite optimal medical management
- Known human immunodeficiency virus (HIV) infection or chronic hepatitis B or C infection
- Active clinically serious infection > grade 2
- Thrombotic or embolic events including cerebral vascular accident or TIAs within the past 6 months
- Pulmonary hemorrhage/bleeding event ≥ grade 2 within 4 weeks of the first dose of sorafenib
- Any other hemorrhage/bleeding event ≥ grade 3 within 4 weeks of the first dose of sorafenib
- Serious non-healing wound, ulcer, or bone fracture
- Evidence or history of bleeding diathesis or coagulopathy
- Major surgery, open biopsy, or significant traumatic injury within 4 weeks of beginning treatment with sorafenib
- Use of St. John's Wort or rifampicin
- Known or suspected allergy to sorafenib or temozolomide
- Any malabsorption problem
- Other active malignancies, or treatment for invasive cancer within the last 2 years
研究計画
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：なし
- 介入モデル：単一グループの割り当て
- 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 |
|---|---|
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実験的：Combination Therapy
In the combined modality portion of the study, patients were administered: Radiation Therapy - 2 Gy/fraction, Single daily fractions M-F, to 60 Gy total Temozolomide - 75 mg/m2 by mouth once daily Patients took a four week break before beginning follow-up systemic therapy: Temozolomide - 150 mg /m2 by mouth on days 1-5 every 28 days for 6 cycles Sorafenib - 400 mg by mouth twice a day for 6 months |
2 Gy/fraction, single daily fractions M-F, to 60 Gy total
In Combined Modality Therapy, administered as 75 mg/m2 by mouth once daily In follow-up systemic therapy, administered as 150 mg/m2 by mouth on days 1-5 every 28 days for 6 cycles
他の名前：
In follow-up systemic therapy, administered as 400 mg by mouth twice daily for 6 months
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 |
|---|---|---|
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Progression-free Survival
時間枠：18 months
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Defined as the duration of time from start of treatment to time of progression or death, whichever comes first.
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18 months
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Overall Survival
時間枠：18 months
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Defined as Day 1 of protocol treatment to date of death from any cause.
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18 months
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Objective Response
時間枠：every 8 weeks until disease progression, estimated 18 months
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The number of patients with complete or partial responses measured from the time of initial response to documented tumor progression. Radiologic response was defined using the Macdonald criteria. The Macdonald criteria divides response into 4 types of response based on imaging (MRI) and clinical features, as follows: 1) complete response (CR); 2) partial response (PR); 3) stable disease (SD); and 4) progression (PD). Criteria: CR: disappearance of all enhancing disease (measurable and non-measurable) sustained for at least 4 weeks, no new lesions. No corticosteroids, clinically stable or improved. PR: >=50% decrease of all measurable enhancing lesions, sustained for at least 4 weeks, no new lesions. Stable or reduced corticosteroids, clinically stable or improved. SD: does not qualify for complete response, partial response or progression. Clinically stable. PD: >= 25% increase in enhancing lesions, any new lesions. Clinical deterioration. |
every 8 weeks until disease progression, estimated 18 months
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協力者と研究者
協力者
捜査官
- スタディチェア：John D. Hainsworth, M.D.、SCRI Development Innovations, LLC
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- SCRI CNS 09
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Radiation Therapyの臨床試験
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UNC Lineberger Comprehensive Cancer CenterNational Institute of Dental and Craniofacial Research (NIDCR)募集
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Universitätsklinikum Hamburg-EppendorfCytoSorbents, Inc募集
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Universitätsklinikum Hamburg-Eppendorf完了