Tivantinib in Treating Patients With Recurrent or Metastatic Breast Cancer
A Phase 2 Study of ARQ 197 in Metastatic Triple-negative Breast Cancer
調査の概要
状態
介入・治療
詳細な説明
PRIMARY OBJECTIVES:
I. To evaluate the activity of tivantinib (ARQ-197) as defined by 6-month progression-free survival (PFS) of participants with triple-negative metastatic breast cancer.
SECONDARY OBJECTIVES:
I. To evaluate objective response based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.
II. To evaluate c-Met and phospho c-Met expression in archival tumor tissue. (Exploratory) III. To evaluate the incidence of c-Met-positive circulating tumor cells at baseline. (Exploratory) IV. To evaluate the effect of ARQ-197 on serum markers relevant to c-Met pathway (hepatocyte growth factor [HGF] and vascular endothelial growth factor [VEGF]). (Exploratory) V. To evaluate phosphatase and tensin homolog (PTEN) loss and PI3K mutations in archival tumor tissue. (Exploratory) VI. To evaluate proportion of participants with basal-like breast cancer. (Exploratory)
OUTLINE: This is a multicenter study.
Patients receive tivantinib orally (PO) twice daily (BID) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection at baseline and periodically during study for c-Met expression, relevant markers (HGF and VEGF), PTEN loss, and PI3K mutation analysis by fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC). Archived tumor tissue samples are also analyzed.
After completion of study treatment, patients are followed up every 6 months.
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
-
-
Massachusetts
-
Boston、Massachusetts、アメリカ、02215
- Dana-Farber Cancer Institute
-
Boston、Massachusetts、アメリカ、02130
- Dana-Farber Cancer Institute Faulkner Hospital
-
-
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:
- Participants must have histologically or cytologically confirmed invasive breast cancer, with recurrent or metastatic disease; participants without pathologic or cytologic confirmation of metastatic disease should have unequivocal evidence of metastasis from physical examination or radiologic evaluation
- Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan
Participants must have recent evidence of progressive disease
- Participants must have received 1-3 prior chemotherapeutic regimens for metastatic breast cancer and must have been off treatment with chemotherapy for at least 14 days before enrollment in the study
- Participants must have discontinued all biologic therapy (including vaccines) at least 14 days before enrollment in the study
- Participants must have discontinued any investigational therapy at least 14 days before enrollment in the study
Participants may have received prior radiation therapy in either the metastatic or early-stage setting
- Radiation therapy must be completed at least 14 days before enrollment in the study
- Participant must not have received radiation to > 25% of his or her bone marrow within 30 days of starting study treatment
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
- Hemoglobin >= 9.0 g/dL
- Absolute neutrophil count >= 1,500/mcL
- Platelets >= 100,000/mcL
- Total bilirubin =< 1.5 times upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 times institutional ULN; for participants with documented liver metastases, AST/ALT =< 5.0 times ULN
- Serum creatinine =< 1.5 times ULN OR creatinine clearance >= 60 mL/min/1.73 m^2 for participants with creatinine levels above institutional normal
Either the primary tumor and/or the metastasis must be triple-negative; the invasive tumor must be hormone-receptor poor, defined as estrogen-receptor negative (ER-) and progesterone-receptor negative (PR-), or staining < 10% by immunohistochemistry (IHC)
- Human epidermal growth factor receptor 2 (HER2) status: the invasive tumor must be HER2-negative, defined as 0 or 1+ by IHC, or FISH < 2.0
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) during the study and for 90 days after the last investigational drug dose received
- Female subjects of childbearing potential must have a negative serum pregnancy test within 21 days of cycle 1 day 1
- Participants on bisphosphonates may continue receiving bisphosphonate therapy during study treatment; bisphosphonate therapy may also be initiated on study treatment if needed
- Confirmed availability of formalin-fixed, paraffin-embedded (FFPE) tumor tissue
- Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
- Participants who have received chemotherapy, biologic, investigational, or radiotherapy within 14 days prior to entering the study
- Participants who are receiving any other investigational agents
Known brain metastases that are untreated, symptomatic, or require therapy to control symptoms
Participants with a history of treated central nervous system (CNS) metastases are eligible
- Treated brain metastases are defined as those having no evidence of progression or hemorrhage for >= 2 months after treatment, and no ongoing requirement for corticosteroids, as ascertained by clinical examination and brain imaging (magnetic resonance imaging or computed tomography [CT] scan) during the screening period
- Treatment for brain metastases may include whole-brain radiotherapy, radiosurgery, or a combination as deemed appropriate by the treating physician
- Participants may be taking anti-convulsant medications, which must be non-enzyme-inducing anti-epileptic drugs
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to ARQ 197
- History of congestive heart failure defined as Class II to IV per New York Heart Association (NYHA) classification; active coronary artery disease (CAD); clinically significant bradycardia or other uncontrolled, cardiac arrhythmia defined as >= grade 3 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, or uncontrolled hypertension; myocardial infarction occurring within 6 months prior to study entry (myocardial infarction occurring > 6 months prior to study entry is permitted)
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women are excluded from this study
- Human immunodeficiency virus (HIV)-positive participants on combination antiretroviral therapy are ineligible
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 (tivantinib)
Patients receive tivantinib 360 mg PO BID on days 1-21.
Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients undergo blood sample collection at baseline and periodically during study for c-Met expression, relevant markers (HGF and VEGF), PTEN loss, and PI3K mutation analysis by FISH and IHC.
Archived tumor tissue samples are also analyzed.
|
相関研究
与えられたPO
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 |
メジャーの説明 |
時間枠 |
---|---|---|
PFS Status
時間枠:Time from start of treatment to time of progression or death, assessed up to 6 months
|
Analyzed using the Kaplan-Meier method.
95% confidence intervals (CI) will be determined.
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
|
Time from start of treatment to time of progression or death, assessed up to 6 months
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
Overall Response Using RECIST v1.1
時間枠:Up to 1 year
|
The 95% confidence intervals should be provided.
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by Conventional CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >/=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
|
Up to 1 year
|
To Evaluate c-Met Expression in Archival Tumor Tissue.
時間枠:Baseline
|
Assessment of ploidy status was done by visual screening of all tumor area; cells with maximum number of signals were recorded.
MET amplification was defined as a MET/CEP7 ratio ≥ 2. Samples having a MET/CEP7 ratio from 1.5 and up to 2 were defined as having relative MET gain.
Samples with a MET/CEP7 ratio of 1 but with more than two copies of each probe were defined as having polysomy of chromosome 7.
|
Baseline
|
To Evaluate Phospho c-Met Expression in Archival Tumor Tissue.
時間枠:Baseline
|
MET amplification was defined as a MET/CEP7 ratio ≥ 2. Samples having a MET/CEP7 ratio from 1.5 and up to 2 were defined as having relative MET gain.
Samples with a MET/CEP7 ratio of 1 but with more than two copies of each probe were defined as having polysomy of chromosome 7.
|
Baseline
|
To Evaluate the Incidence of c-Met Positive Circulating Tumor Cells.
時間枠:Baseline
|
Baseline
|
協力者と研究者
捜査官
- 主任研究者:Sara Tolaney、Dana-Farber Cancer Institute
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
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。
IV期乳がんの臨床試験
-
University of TartuTartu University Hospital; Estonian Science Foundation募集
-
Mayo ClinicNational Cancer Institute (NCI)募集子宮頸部腺扁平上皮がん | 特に明記されていない子宮頸部扁平上皮癌 | 再発子宮頸がん | ステージ IB3 子宮頸がん FIGO 2018 | ステージ II 子宮頸がん FIGO 2018 | ステージ IIA 子宮頸がん FIGO 2018 | Stage IIA1 子宮頸がん FIGO 2018 | Stage IIA2 子宮頸がん FIGO 2018 | ステージ IIB 子宮頸がん FIGO 2018 | ステージ III 子宮頸がん FIGO 2018 | ステージ IIIA 子宮頸がん FIGO 2018 | Stage IIIB 子宮頸がん FIGO 2018 | ステージ IIIC 子宮頸がん FIGO 2018 | Stage... およびその他の条件アメリカ
研究室のバイオマーカー分析の臨床試験
-
ORIOL BESTARD完了腎臓移植 | CMV感染スペイン, ベルギー
-
Central and North West London NHS Foundation TrustBritish HIV Association (BHIVA)まだ募集していませんHIV感染症 | B型肝炎
-
Hvidovre University HospitalElsassFonden終了しました
-
McGill University Health Centre/Research Institute...Northwestern University募集
-
Nantes University Hospital完了
-
Fundació Sant Joan de DéuStanley Medical Research Institute; Parc Sanitari Sant Joan de Déu; Hospital Sant Joan de Deu完了