Combination of Weekly Paclitaxel With Neratinib and Trastuzumab in Women With Metastatic HER2-positive Breast Cancer
A Phase I Dose-Escalation Study Evaluating the Combination of Weekly Paclitaxel With Neratinib and Trastuzumab in Women With Metastatic HER2-positive Breast Cancer
調査の概要
詳細な説明
Patients will receive concurrent therapy with paclitaxel (80 mg/m2 IV on days 1, 8, and 15 of a 28-day cycle), trastuzumab (4 mg/kg IV loading dose, then 2 mg/kg IV weekly), and neratinib. The neratinib dose-escalation will include 4 dose levels (120 mg, 160 mg, 200 mg, and 240 mg) as a daily oral dose.
The neratinib dose-escalation for the study will proceed on the basis of dose-limiting toxicity (DLT) during cycle 1. DLT will be defined as the occurrence of 1 or more of the following events during cycle 1: any grade diarrhea that is associated with fever or dehydration; grade 3 diarrhea lasting more than 2 days on optimal medical therapy; grade 4 diarrhea of any duration; grade 3 or 4 neutropenia associated with fever; grade 4 neutropenia lasting more than 7 days; grade 4 thrombocytopenia; grade 3 or 4 non-hematological toxicity; or any toxicity-related delay of more than 2 weeks to initiate cycle 2. Patients will be enrolled at the next dose level when all evaluable patients at the same dose level have completed the first treatment cycle. Enrolled patients will remain on the assigned dose level treatment until toxicity or disease progression.
研究の種類
入学 (実際)
段階
- フェーズ 1
連絡先と場所
研究場所
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New Jersey
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New Brunswick、New Jersey、アメリカ、08901
- Cancer Institute of New Jersey
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Pennsylvania
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Pittsburgh、Pennsylvania、アメリカ、15212
- NSABP Foundation, Inc.
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Pittsburgh、Pennsylvania、アメリカ、15232-1305
- University of Pittsburgh
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West Virginia
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Morgantown、West Virginia、アメリカ、26506-9162
- West Virginia University Hospitals
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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:
- Co-morbid conditions should be taken into consideration, but not the diagnosis of metastatic breast cancer.
- Patients of reproductive potential must agree to use an effective non-hormonal method of contraception during therapy and for at least 6 months after the last dose of study therapy.
- The ECOG performance status must be 0, 1, or 2.
- Patients must have the ability to swallow oral medication.
- Patients must have histologic or cytologic confirmation of the diagnosis of invasive adenocarcinoma of the breast.
- There must be documentation that the patient has evidence (measurable or non-measurable) of metastatic breast cancer. Histologic confirmation of metastatic disease is not required.
- Patients must have ER analysis performed on the primary tumor prior to study entry. If ER analysis is negative, then PgR analysis must also be performed. (Patients are eligible with either hormone receptor-positive or hormone receptor-negative tumors.)
- Breast cancer must be determined to be HER2-positive prior to study entry. Assays using FISH or CISH require gene amplification. Assays using IHC require a strongly positive (3+) staining score.
- At the time of study entry, blood counts performed within 4 weeks prior to study entry must meet the following criteria: ANC must be greater than or equal to 1000/mm3; Platelet count must be greater than or equal to 100,000/mm3; Hemoglobin must be greater than or equal to 9 g/dL
- The following criteria for evidence of adequate hepatic function performed within 4 weeks prior to study entry must be met: total bilirubin must be less than or equal to 1.5 x ULN; AST and ALT must be less than or equal to 2.5 x ULN for the lab or less than or equal to 5 x ULN if liver metastasis
- Serum creatinine performed within 4 weeks prior to study entry must be less than or equal to 1.5 x ULN for the lab.
- The LVEF assessment by 2-D echocardiogram or MUGA scan performed within 90 days prior to study entry must be greater than or equal to 50% regardless of the facility's LLN.
Exclusion Criteria:
- Previous therapy with neratinib for any malignancy.
- Symptomatic brain metastases or brain metastases requiring chronic steroids to control symptoms.
- Active hepatitis B or hepatitis C with abnormal liver function tests.
- Intrinsic lung disease resulting in dyspnea.
- Active infection or chronic infection requiring chronic suppressive antibiotics.
- Malabsorption syndrome, ulcerative colitis, inflammatory bowel disease, resection of the stomach or small bowel, or other disease or condition significantly affecting gastrointestinal function.
- Persistent greater than or equal to grade 2 diarrhea regardless of etiology.
- Sensory or motor neuropathy greater than or equal to grade 2, as defined by the NCI CTCAE v3.0.
- Conditions that would prohibit intermittent administration of corticosteroids for paclitaxel premedication.
- Chronic daily treatment with corticosteroids with a dose of greater than or equal to 10 mg/day methylprednisolone equivalent (excluding inhaled steroids).
- Uncontrolled hypertension defined as a systolic BP greater than 150 mmHg or diastolic BP greater than 90 mmHg, with or without anti-hypertensive medications (Patients with hypertension that is well controlled on medication are eligible.)
- Cardiac disease (history of and/or active disease) that would preclude the use of any of the drugs included in the treatment regimen. This includes but is not confined to: Active cardiac disease: symptomatic angina pectoris within the past 90 days that required the initiation of or increase in anti-anginal medication or other intervention; ventricular arrhythmias except for benign premature ventricular contractions; supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication; conduction abnormality requiring a pacemaker; valvular disease with documented compromise in cardiac function; and symptomatic pericarditis. History of cardiac disease: myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LV function; history of documented CHF; and documented cardiomyopathy
- Other nonmalignant systemic disease that would preclude the patient from receiving study treatment or would prevent required follow up.
- Pregnancy or lactation at the time of study entry. (Note: Pregnancy testing should be performed within 14 days prior to study entry according to institutional standards for women of childbearing potential.)
- The investigator should assess the patient to determine if she has any psychiatric or addictive disorder or other condition that, in the opinion of the investigator, would preclude her from meeting the study requirements.
- Use of any investigational agent within 4 weeks prior to study entry.
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 |
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実験的:Neratinib
Paclitaxel (80 mg/m2 IV on days 1, 8, and 15 every 28 days) and trastuzumab (4 mg/kg/ loading dose, then 2 mg/kg) IV weekly beginning on day 1 of paclitaxel, neratinib orally daily beginning on day 1 of paclitaxel until disease progression.
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80 mg/m2 IV on days 1, 8, and 15 every 28 days until disease progression.
4 mg/kg IV loading dose, then 2 mg/kg IV weekly until disease progression.
Dose level 1: 120 mg/day orally; Dose level 2: 160 mg/day orally; Dose level 3: 240 mg/day orally; Dose level 4: 200 mg/day orally.
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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 |
---|---|---|
Safety and tolerability of the three-drug combination
時間枠:Through 6 months after last dose
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Number of patients experiencing dose limiting toxicities (DLT).
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Through 6 months after last dose
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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 response rate
時間枠:Measured at 24 weeks from start of therapy.
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Number of patients with disappearance of all target lesions; Number of patients with at least a 30% decrease in the sum of the longest diameter (LD) of target lesions; patients with neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as a reference the smallest sum LD since baseline.
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Measured at 24 weeks from start of therapy.
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Progression-free interval
時間枠:Time to disease progression up to 15 months.
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Number of patients with at least a 20% increase in the sum of the LD of target lesions, taking as a reference the smallest sum LD recorded since baseline or the appearance of one or more new lesions.
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Time to disease progression up to 15 months.
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協力者と研究者
スポンサー
協力者
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。
乳がんの臨床試験
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Tianjin Medical University Cancer Institute and...Guangxi Medical University; Sun Yat-sen University; Chinese PLA General Hospital; The First Affiliated... と他の協力者完了
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Jonsson Comprehensive Cancer CenterNational Cancer Institute (NCI); Highlight Therapeutics積極的、募集していない平滑筋肉腫 | 悪性末梢神経鞘腫瘍 | 滑膜肉腫 | 未分化多形肉腫 | 骨の未分化高悪性度多形肉腫 | 粘液線維肉腫 | II期の体幹および四肢の軟部肉腫 AJCC v8 | III期の体幹および四肢の軟部肉腫 AJCC v8 | IIIA 期の体幹および四肢の軟部肉腫 AJCC v8 | IIIB 期の体幹および四肢の軟部肉腫 AJCC v8 | 切除可能な軟部肉腫 | 多形性横紋筋肉腫 | 切除可能な脱分化型脂肪肉腫 | 切除可能な未分化多形肉腫 | 軟部組織線維肉腫 | 紡錘細胞肉腫 | ステージ I 後腹膜肉腫 AJCC (American Joint Committee on Cancer) v8 | 体幹および四肢の I 期軟部肉腫 AJCC v8 | ステージ... およびその他の条件アメリカ
Paclitaxelの臨床試験
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Ajou University School of Medicine積極的、募集していない
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Medtronic Endovascular完了
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Conor Medsystems終了しました
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Hemoteq AG完了冠動脈疾患 | 冠動脈硬化症 | 冠動脈アテローム性動脈硬化症 | 冠動脈再狭窄ドイツ, フランス
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Fondazione Evidence per Attività e Ricerche Cardiovascolari...わからない
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EBG MedAustron GmbHLandesklinkum Wiener Neustadt募集
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Xijing Hospital積極的、募集していない