PIK3CA 変異を有する癌における潜在的な標的治療としてのコパンリシブの試験 (MATCH-サブプロトコル Z1F)
PIK3CA 変異を有する腫瘍患者におけるコパンリシブの第 II 相試験 (PTEN 喪失は許容される)
This phase II MATCH treatment trial identifies the effects of copanlisib hydrochloride (copanlisib) in patients whose cancer has a genetic change called PIK3CA mutation. Copanlisib may stop the growth of cancer cells by blocking PIK3, a protein needed for cell growth. Researchers hope to learn if copanlisib will shrink this type of cancer or stop its growth.
調査の概要
状態
詳細な説明
PRIMARY OBJECTIVE:
I. To evaluate the proportion of patients with objective response (OR) to targeted study agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma.
SECONDARY OBJECTIVES:
I. To evaluate the proportion of patients alive and progression free at 6 months of treatment with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple myeloma.
II. To evaluate time until death or disease progression. III. To identify potential predictive biomarkers beyond the genomic alteration by which treatment is assigned or resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and imaging-based assessment platforms.
IV. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes from pre- through post-therapy imaging can predict objective response and progression free survival and to evaluate the association between pre-treatment radiomic phenotypes and targeted gene mutation patterns of tumor biopsy specimens.
OUTLINE:
Patients receive copanlisib intravenously (IV) over 1 hour on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo tumor biopsies at screening and end of treatment and computed tomography (CT) or magnetic resonance imaging (MRI) at baseline, every 2 cycles for the first 26 cycles, and then every 3 cycles thereafter until progressive disease or start of another MATCH treatment step.
After completion of study treatment, patients are followed up every 3 months if less than 2 years from study entry, and then every 6 months for year 3 from study entry.
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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Pennsylvania
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Philadelphia、Pennsylvania、アメリカ、19103
- ECOG-ACRIN Cancer Research Group
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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:
- Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol
- Patients must have PIK3CA mutation as determined via the MATCH Master Protocol
- Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block)
- Patients should stop using herbal medications at least 7 days prior to the first dose of copanlisib. Herbal medications include, but are not limited to: St. John's Wort, Kava, ephedra, gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, black cohosh and ginseng
- Patients with type I or II diabetes mellitus must have glycosylated hemoglobin A1c (HbA1c) =< 8.5% within 28 days from registration
- Absolute neutrophil count (ANC) >= 1.5 x 10^9 /L
- Platelets >= 100x10^9/L
- Hemoglobin (Hb) > 9 g/dl
- Total serum bilirubin < 2.0 mg/dL
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x upper limit of normal (ULN) (< 5 x ULN in patients with liver metastases)
- Serum creatinine < 1.5 x ULN
- Men and women of child-bearing potential must agree to use contraception while receiving study treatment and for 1 month after the last dose of copanlisib
Exclusion Criteria:
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Patients must not have known hypersensitivity to copanlisib or compounds of similar chemical or biologic composition
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Patients must not have had prior therapy with copanlisib or other PI3K inhibitors, AKT inhibitors or mTOR inhibitors
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Patients must not have activating KRAS mutations
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Patients must not have HER2 positive (3+ by immunohistochemistry [IHC] or fluorescence in situ hybridization [FISH] ratio >= 2) breast cancer
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Patients must not have indolent non-Hodgkin lymphoma (NHL) (follicular lymphoma, small lymphocytic lymphoma [SLL]/chronic lymphocytic leukemia [CLL], lymphoplasmacytic lymphoma [LPL], marginal zone lymphoma) or DLBCL (diffuse large B cell lymphoma)
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Patients must not be on strong inhibitors or inducers of CYP3A4 within two weeks prior to start of study treatment and for the duration of study treatment
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Patients must not be on anti-arrhythmic therapy other than digoxin or beta-blockers
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Patients with non-healing wound, ulcer, or bone fracture are not eligible
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Patients with history of or current interstitial pneumonitis are not eligible
- NOTE: For solid tumors, cytomegalovirus (CMV) polymerase chain reaction (PCR) can be obtained at the discretion of treating physician or local institutional guidelines
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：Treatment (copanlisib)
Patients receive copanlisib IV over 1 hour on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo tumor biopsies at screening and end of treatment and CT or MRI at baseline, every 2 cycles for the first 26 cycles, and then every 3 cycles thereafter until progressive disease or start of another MATCH treatment step. |
Undergo CT
他の名前：
Undergo MRI
他の名前：
Undergo tumor biopsy
他の名前：
Given IV
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 |
|---|---|---|
|
Overall Response Rate (ORR)
時間枠：Tumor assessments occurred at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 30 months post registration
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ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among analyzable (ie, eligible, treated and PIK3CA mutation status confirmed) patients. Objective response is defined consistent with Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Details about how to define complete response and partial response can be found in the master protocol. 90% two-sided binomial exact confidence interval is calculated for ORR. |
Tumor assessments occurred at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 30 months post registration
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Progression Free Survival (PFS)
時間枠：Assessed at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration
|
PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Please refer to the protocol for detailed definitions of disease progression. |
Assessed at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration
|
|
6-month Progression-Free Survival (PFS) Rate
時間枠：Assessed at baseline, then every 2 cycles for the first 26 cycles, and every 3 cycles thereafter until disease progression, up to 3 years post registration, from which 6-month PFS rate is determined
|
Progression-free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in NeuroOncology criteria for glioblastoma patients. Please refer to the protocol for detailed definitions of disease progression. 6 month PFS rate was estimated using the Kaplan-Meier method, which can provide a point estimate for any specific time point. |
Assessed at baseline, then every 2 cycles for the first 26 cycles, and every 3 cycles thereafter until disease progression, up to 3 years post registration, from which 6-month PFS rate is determined
|
協力者と研究者
捜査官
- 主任研究者：Senthilkumar Damodaran、ECOG-ACRIN Cancer Research Group
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (推定)
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 (実際)
学習記録の更新
投稿された最後の更新 (実際)
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
- NCI-2022-06209
- U10CA180820 (米国 NIH グラント/契約)
- U24CA196172 (米国 NIH グラント/契約)
- NCI-2022-06209 (レジストリ識別子：CTRP (Clinical Trial Reporting Program))
- EAY131-Z1F (その他の識別子：CTEP)
- EAY131-Z1F (その他の識別子：ECOG-ACRIN Cancer Research Group)
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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