Everolimus and Gefitinib in Treating Patients With Progressive Glioblastoma Multiforme or Progressive Metastatic Prostate Cancer
A Phase I/II Trial to Assess the Tolerability of RAD 001 With Gefitinib in Patients With Glioblastoma Multiforme and Prostate Cancer and Efficacy in Patients With Castrate Metastatic Prostate Cancer
RATIONALE: Everolimus may stop the growth of tumor cells by stopping blood flow to the tumor. Gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Combining everolimus with gefitinib may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of everolimus when given together with gefitinib and to see how well they work in treating patients with progressive glioblastoma multiforme or (progressive metastatic prostate cancer closed to accrual 10/19/06).
調査の概要
詳細な説明
OBJECTIVES:
Primary
- Determine the maximum tolerated dose of everolimus when given in combination with gefitinib in patients with progressive glioblastoma multiforme or (progressive castrate metastatic prostate cancer -closed to accrual as of 10/19/2006). (Phase I)
- Determine the safety and efficacy of this regimen in patients with progressive glioblastoma multiforme or (progressive castrate metastatic prostate cancer - closed to accrual as of 10/19/2006). (Phase II)
Secondary
- Determine whether a pharmacokinetic interaction exists between everolimus and gefitinib in patients treated with this regimen.
- Determine the association between clinical outcomes and markers that may predict sensitivity of a tumor in patients treated with this regimen.
- Determine the pharmacodynamic effects of this regimen on post-therapy tumor specimens and peripheral blood mononuclear cells from these patients.
OUTLINE: This is a phase I, open-label, non-randomized, dose-escalation study of everolimus followed by a phase II study.
- Phase I: Patients receive oral everolimus on day 1 and oral gefitinib once daily on days 8-21. Beginning on day 22, patients receive oral everolimus once weekly and oral gefitinib once daily. Treatment with the combination continues in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of everolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
- Phase II (prostate cancer patients only) (closed to accrual as of 10/19/2006): Patients receive oral everolimus (at the MTD determined in phase I) once weekly and oral gefitinib once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.
研究の種類
入学 (実際)
段階
- フェーズ2
- フェーズ 1
連絡先と場所
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
DISEASE CHARACTERISTICS:
Histologically confirmed diagnosis of 1 of the following:
Glioblastoma multiforme (GBM) (phase I only)
- Progressive disease despite standard therapy
Progressive disease based on 1 of the following:
- New or progressive (25% bidimensional increase) soft tissue masses on CT scan or MRI
- New or prior lesions that have increased in size by physical examination
- Patients who had prior interstitial brachytherapy or stereotactic radiosurgery must have confirmation of true disease progression (rather than radiation necrosis) by positron-emission tomography scan, thallium scanning, magnetic resonance spectroscopy, or surgical documentation
Castrate metastatic prostate cancer (closed to accrual as of 10/19/2006) (phase I and II)
- Progressive disease despite standard therapy AND castrate levels < 50 ng/dL of testosterone
Progressive disease based on 1 or more of the following:
- A minimum of 3 rising levels of prostate-specific antigen (PSA) that are obtained 1 or more weeks apart OR 2 rising PSA values obtained more than 1 month apart with at least a 25% increase over the range of values
- New or progressive (25% bidimensional increase) soft tissue masses on CT scan or MRI
- New metastatic lesions
- Patients on an antiandrogen as part of initial therapy must show disease progression after discontinuation of the antiandrogen
- Patients who have not undergone surgical orchiectomy must continue with medical therapy (e.g., gonadotropin-releasing hormone analogs) to maintain castrate levels of serum testosterone
- No brain metastases
PATIENT CHARACTERISTICS:
Age
- Over 18
Performance status
- Karnofsky 70-100%
Life expectancy
- More than 3 months
Hematopoietic
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- WBC ≥ 3,000/mm^3
Hepatic
- ALT and AST ≤ 2.5 times upper limit of normal (ULN)
- Bilirubin ≤ 1.5 mg/dL
Renal
- Creatinine within 1.5 times ULN (< 1.95 mg/dL at MSKCC)
Cardiovascular
- No significant cardiovascular disease
- No congestive heart failure
- No New York Heart Association class III or IV cardiac disease
- No active angina pectoris
- No myocardial infarction within the past 6 months
Other
- Not pregnant
- Negative pregnancy test
- Fertile patients must use effective contraception
- No serious medical illness
- No severe infection
- No severe malnutrition
No other active malignancy except non-melanoma skin cancer
- Patients are not considered to have an active malignancy if they have completed prior therapy and currently have a < 30% risk for relapse
PRIOR CONCURRENT THERAPY:
Biologic therapy
- No concurrent biological therapy
- No concurrent immunotherapy
Chemotherapy
- No concurrent chemotherapy
Endocrine therapy
- See Disease Characteristics
Radiotherapy
- See Disease Characteristics
- More than 4 weeks since prior radiotherapy
- No concurrent radiotherapy
Surgery
- See Disease Characteristics
- Prior recent resection of recurrent or progressive GBM allowed provided patient has recovered
- More than 4 weeks since prior major surgery
Other
- Recovered from all prior therapy
- More than 4 weeks since prior investigational anticancer drugs
- No concurrent anticonvulsant that interacts with CYP3A4 (e.g., phenytoin, carbamazepine, or phenobarbital)
- No other concurrent cytotoxic therapy
- No other concurrent investigational or commercial agents or therapies for the malignancy
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 |
|---|---|
|
実験的:Everolimus (RAD-001) and Gefitinib
•Phase I: Patients receive oral everolimus on day 1 and oral gefitinib once daily on days 8-21. Beginning on day 22, patients receive oral everolimus once weekly and oral gefitinib once daily. Treatment with the combination continues in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of everolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. •Phase II (prostate cancer patients only) (closed to accrual as of 10/19/2006): Patients receive oral everolimus (at the MTD determined in phase I) once weekly and oral gefitinib once daily. Treatment continues in the absence of disease progression or unacceptable toxicity. |
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 |
|---|---|---|
|
Overall Objective Response
時間枠:2 years
|
Response will be evaluated in this study using the new international criteria Response Evaluation Criteria in Solid Tumors (RECIST)
|
2 years
|
協力者と研究者
捜査官
- 主任研究者:Lauren E. Abrey, MD、Memorial Sloan Kettering Cancer Center
- 主任研究者:Howard I. Scher, MD、Memorial Sloan Kettering Cancer Center
- 主任研究者:Neal Rosen, MD、Memorial Sloan Kettering Cancer Center
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
- 04-010
- MSKCC-04010
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