Safety Study of Ridaforolimus in Patients With Advanced, Refractory or Recurrent Malignancies (MK-8669-001 AM5)(COMPLETED)
A Phase I, Sequential Cohort, Dose Escalation Trial to Determine the Safety, Tolerability, and Maximum Tolerated Dose of Weekly Administration of AP23573, an mTOR Inhibitor, in Patients With Refractory or Advanced Malignancies
調査の概要
詳細な説明
The primary objectives of the study are to determine the safety, tolerability, and MTD of ridaforolimus when administered once weekly for 4 weeks (4 week cycle). The secondary objectives of the study are to characterize the pharmacokinetic profile of ridaforolimus, to evaluate potential pharmacodynamic markers of ridaforolimus, and to obtain preliminary information on the antineoplastic activity of ridaforolimus.
Protocol Outline: This is a dose-escalation study. Patients receive ridaforolimus over 30 minutes by intravenous infusion once weekly for 8 weeks (two 4-week cycles). If tolerated, a total of at least 2 cycles will be administered (8-week treatment period). Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity.
研究の種類
入学 (実際)
段階
- フェーズ 1
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:
(Patients must meet each of the following criteria to be eligible for participation in the study).
- Male or female patients, ≥ 18 years of age.
- Patients with a documented measurable or evaluable malignancy, including myeloma or lymphoma, that is recurrent, advanced, or metastatic.
- Patients with disease that is currently refractory to, or not amenable to, standard therapy.
- Patients with disease that is currently not amenable to surgical intervention.
- Patients with Karnofsky performance status of ≥ 70% (Eastern Cooperative Oncology Group [ECOG] performance status of 0 or 1) and an anticipated life expectancy of ≥ 3 months.
- Patients either not of childbearing potential, or agreeing to use a medically effective method of contraception.
- Patients with the ability to understand and give written informed consent.
Exclusion Criteria:
(Patients meeting any of the following criteria are ineligible for participation in the study)
- Women who are pregnant or lactating.
- Patients with primary central nervous system (CNS) malignancies. Patients with leukemia, any form.
- Patients with certain hematologic abnormalities.
- Patients with certain serum chemistry abnormalities at baseline.
- Patients with known or suspected hypersensitivity to either drugs formulated with polysorbate 80 (Tween 80) or any other excipient contained in the test drug formulation.
- Patients with known hypersensitivity to macrolide antibiotics (e.g., clarithromycin, erythromycin, azithromycin).
- Patients with significant cardiovascular disease.
- Patients with active CNS metastases (or leptomeningeal disease) not controlled by prior surgery or radiotherapy. Note: Patients with treated brain metastases will be eligible if they are on a stable dose of corticosteroids or are without change in brain disease status for at least 4 weeks following related therapy (e.g., whole brain radiation, surgery).
- Patients with known human immunodeficiency virus (HIV) infection.
- Patients with any active infection.
- Patients with inadequate recovery from any prior surgical procedure, or patients having undergone any major surgical procedure within 2 weeks prior to study entry. Note: Patients having undergone recent placement of a central venous access port will be considered eligible for enrollment if they have recovered.
- Patients who have any other life-threatening illness or organ system dysfunction which, in the opinion of the Investigator, would either compromise the patient's safety or interfere with evaluation of the safety of the test drug.
- Patients with a psychiatric disorder or altered mental status that would preclude understanding of the informed consent process and/or completion of the necessary studies.
- Patients with the inability, in the opinion of the Investigator, to comply with the protocol requirements.
Drugs and Other Treatments to be Excluded (Either during or within 4 weeks prior to study entry, unless otherwise noted)
- Chemotherapeutic agents (standard or experimental).
- Other antineoplastic agents.
- Immunotherapy (including vaccines) or biological response modifier therapy.
- Systemic replacement hormonal therapy for life-threatening non-oncology diseases.
- Herbal preparations or related over-the-counter (OTC) preparations containing herbal ingredients (e.g., St John's Wort) during or within 2 weeks prior to study entry.
- Any prior therapy with rapamycin, CCI-779, or any other rapamycin analog.
- Any other experimental therapy during the course of the study.
- Radiotherapy for the primary malignancy or metastases.
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:非ランダム化
- 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:Cohort 1: Ridaforolimus 6.25 mg
|
Administered intravenously once weekly for 4 weeks (1 cycle). In the absence of disease progression or unacceptable toxicity, patients could continue to receive additional cycles.
他の名前:
|
実験的:Cohort 2: Ridaforolimus 12.5 mg
|
Administered intravenously once weekly for 4 weeks (1 cycle). In the absence of disease progression or unacceptable toxicity, patients could continue to receive additional cycles.
他の名前:
|
実験的:Cohort 3: Ridaforolimus 25 mg
|
Administered intravenously once weekly for 4 weeks (1 cycle). In the absence of disease progression or unacceptable toxicity, patients could continue to receive additional cycles.
他の名前:
|
実験的:Cohort 4: Ridaforolimus 50 mg
|
Administered intravenously once weekly for 4 weeks (1 cycle). In the absence of disease progression or unacceptable toxicity, patients could continue to receive additional cycles.
他の名前:
|
実験的:Cohort 5: Ridaforolimus 100 mg
|
Administered intravenously once weekly for 4 weeks (1 cycle). In the absence of disease progression or unacceptable toxicity, patients could continue to receive additional cycles.
他の名前:
|
実験的:Cohort 6: Ridaforolimus 75 mg
|
Administered intravenously once weekly for 4 weeks (1 cycle). In the absence of disease progression or unacceptable toxicity, patients could continue to receive additional cycles.
他の名前:
|
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 |
時間枠 |
---|---|
Maximum Tolerated Dose (MTD)
時間枠:Cycle 1 (within the first 4 weeks)
|
Cycle 1 (within the first 4 weeks)
|
Number of Participants Reporting Adverse Events (AE)
時間枠:Throughout study duration and up to approximately 1 month after the last dosing cycle (Cycle 1 Day 1 to approximately 10 months)
|
Throughout study duration and up to approximately 1 month after the last dosing cycle (Cycle 1 Day 1 to approximately 10 months)
|
Number of Participants Discontinuing Due to AEs
時間枠:Throughout study duration (Cycle 1 Day 1 to approximately 9 months)
|
Throughout study duration (Cycle 1 Day 1 to approximately 9 months)
|
二次結果の測定
結果測定 |
時間枠 |
---|---|
Best Overall Tumor Response
時間枠:8 weeks
|
8 weeks
|
Maximum Concentration (Cmax) of Ridaforolimus
時間枠:Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1
|
Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1
|
Area Under the Curve (AUC[0 to Infinity]) of Ridaforolimus
時間枠:Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1
|
Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1
|
Apparent Terminal Half-Life (t1/2) of Ridaforolimus
時間枠:Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1
|
Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1
|
Clearance (CL) of Ridaforolimus
時間枠:Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1
|
Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1
|
Volume of Distribution at Steady State (Vss) of Ridaforolimus
時間枠:Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1
|
Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 1
|
Phosphorylated 4E Binding Protein 1 (Phospho-4E-BP1) Blood Levels
時間枠:Screening, Cycle 1 Days 1, 2, 3, 6/7, 8; Cycle 2 Day 1
|
Screening, Cycle 1 Days 1, 2, 3, 6/7, 8; Cycle 2 Day 1
|
協力者と研究者
スポンサー
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
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