Phase 2 Study of AMG 386 Plus Paclitaxel With or Without Bevacizumab as First Line Therapy in Her2-Negative Breast Cancer Patients
A Randomized, 4-Arm, Placebo-Controlled Phase 2 Trial of AMG 386 in Combination With Bevacizumab and Paclitaxel or AMG 386 Plus Paclitaxel as First-Line Therapy in Subjects With Her2-Negative, Metastatic or Locally Recurrent Breast Cancer
This is a phase 2, randomized, placebo controlled, multi-center study to estimate the treatment effect and evaluate the safety and tolerability of AMG 386 in combination with paclitaxel and paclitaxel/bevacizumab in the treatment of subjects with Her2-negative metastatic or locally recurrent breast cancer.
AMG 386 is a man-made medication that is designed to stop the development of blood vessels in cancer tissues. Cancer tissues rely on the development of new blood vessels, a process called angiogenesis, to obtain a supply of oxygen and nutrients to grow.
調査の概要
状態
詳細な説明
Primary Objective: To estimate the treatment effect as measured by progression free survival (PFS) of subjects receiving AMG 386 (at 2 doses) in combination with paclitaxel + bevacizumab relative to paclitaxel + bevacizumab + placebo.
Secondary Objective(s):
- To compare the treatment effect as measured by PFS of subjects receiving open-label AMG 386 in combination with paclitaxel relative to paclitaxel + bevacizumab + placebo
- To compare the treatment effect as measured by PFS of subjects receiving AMG 386 in combination with paclitaxel and bevacizumab relative to paclitaxel + AMG 386
- To evaluate the safety and tolerability of the combination and non-bevacizumab regimens
- To estimate other measures (RR, DOR, TTR, TTP) of treatment effect
- To evaluate the pharmacokinetics (PK) of AMG 386 and bevacizumab when used in combination
- To estimate the incidence of anti-AMG386 antibody formation
Exploratory Objective(s):
- To explore the pharmacodynamic (PD) response as assessed by changes in blood levels of angiogenic cytokines, tumor apoptosis, and other markers
- To explore the association of histological features and selected immunologic, biochemical, pharmacogenetic, or angiogenic markers in tumor biopsies, plasma, or serum samples with safety and/or efficacy outcomes
Study Design:
This is a phase 2, randomized, placebo controlled, multi-center study to estimate the treatment effect and evaluate the safety and tolerability of AMG 386 in combination with paclitaxel and paclitaxel/bevacizumab in the treatment of subjects with Her2-negative metastatic or locally recurrent breast cancer.
Two hundred twenty subjects will be randomized 1:1:1:1 to each of the following arms:
Arm A: Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 10 mg/kg IV QW Arm B: Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 3 mg/kg IV QW Arm C: Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 placebo IV QW Arm D: Paclitaxel 90 mg/m² IV QW (3 on/1 off) + Open Label AMG 386 10 mg/kg IV QW To maintain the double-blind in arms A, B, and C, each subject will be infused weekly with a volume of investigational product equivalent to 10 mg/kg AMG 386 IV. Arm D will receive open label AMG 386 and will not receive a placebo for bevacizumab.
Subjects will be discontinued from study treatment at any time for radiographic disease progression, clinical progression, unacceptable toxicity, subject withdrawal of consent, or death.
Subjects alive at the time of discontinuation of all study medications will be followed for up to 48 months from the date of the last subject enrolled into the trial to evaluate overall survival.
Radiological imaging to assess disease status will be performed every 8 weeks ± 7 days (2 cycles) for 2 years and then every 4 months ± 1 month thereafter during the study until subjects develop radiographic disease progression per the modified RECIST criteria. In addition, any subject who discontinues study drug treatment prior to disease progression will continue to have radiological imaging performed every 8 weeks ± 7 days during the long term follow up period if the subject has not been in the study for 2 years until the subject develops radiographic disease progression or begins a new treatment. If the subject has been on study for 2 years, radiological imaging every 4 months ± 1 month will be performed during long term follow-up period until the subject develops radiographic disease progression or begins a new treatment.
The overall study design is described by a study schema immediately following this synopsis. Amgen Global Safety (AGS) will charter a data review team (DRT) that is independent of the team conducting the study and will review unblinded safety data after 20, 40, and 80 subjects have been randomized and have had the opportunity to receive at least 1 cycle (4 weeks) of study treatment.
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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Arizona
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Litchfield Park、Arizona、アメリカ、85340
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Tucson、Arizona、アメリカ、85724
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Arkansas
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Hot Springs、Arkansas、アメリカ、71913
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Little Rock、Arkansas、アメリカ、72205
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California
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Campbell、California、アメリカ、95008
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Los Angeles、California、アメリカ、90095
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Murrieta、California、アメリカ、92562
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Santa Maria、California、アメリカ、93454
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Connecticut
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New Haven、Connecticut、アメリカ、06520
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Stamford、Connecticut、アメリカ、06902
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Florida
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Orlando、Florida、アメリカ、32804
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Minnesota
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Robbinsdale、Minnesota、アメリカ、55422
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Nevada
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Henderson、Nevada、アメリカ、89052
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New Hampshire
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Lebanon、New Hampshire、アメリカ、03756
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Nashua、New Hampshire、アメリカ、03061
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New Jersey
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Edison、New Jersey、アメリカ、08820
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Mountain Lakes、New Jersey、アメリカ、07046
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North Carolina
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Asheville、North Carolina、アメリカ、28806
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Charlotte、North Carolina、アメリカ、28203
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Pennsylvania
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Hershey、Pennsylvania、アメリカ、17033
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Philadelphia、Pennsylvania、アメリカ、19106
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South Carolina
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Columbia、South Carolina、アメリカ、29210
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Texas
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Richardson、Texas、アメリカ、75080
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San Antonio、Texas、アメリカ、78229
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Sugar Land、Texas、アメリカ、77479
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Utah
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Ogden、Utah、アメリカ、84403
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Guildford、イギリス、GU2 7XX
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Leicester、イギリス、LE1 5WW
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London、イギリス、W6 8RF
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London、イギリス、NW1 2PG
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Manchester、イギリス、M20 4BX
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Northwood、イギリス、HA6 2RN
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Nottingham、イギリス、NG5 1PB
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Karnataka
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Bangalore、Karnataka、インド、560 029
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Maharashtra
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Miraj、Maharashtra、インド、416 410
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Mumbai、Maharashtra、インド、400 012
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Nagpur、Maharashtra、インド、440 012
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Pune、Maharashtra、インド、411 001
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Rajasthan
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Jaipur、Rajasthan、インド、302 013
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Jaipur、Rajasthan、インド、302 004
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Maastricht、オランダ、6229 HX
- Research Site
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South Australia
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Kurralta Park、South Australia、オーストラリア、5037
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Victoria
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Epping、Victoria、オーストラリア、3076
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Fitzroy、Victoria、オーストラリア、3065
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Footscray、Victoria、オーストラリア、3011
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Malvern、Victoria、オーストラリア、3144
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Western Australia
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Perth、Western Australia、オーストラリア、6000
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Innsbruck、オーストリア、6020
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Wels、オーストリア、4600
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Wien、オーストリア、1090
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Madrid、スペイン、28033
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AndalucÃ-a
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Jaén、AndalucÃ-a、スペイン、23007
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Cataluña
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Sabadell、Cataluña、スペイン、08208
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Galicia
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Santiago de Compostela、Galicia、スペイン、15706
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Herlev、デンマーク、2730
- Research Site
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Gyula、ハンガリー、5700
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Kaposvar、ハンガリー、7400
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Szombathely、ハンガリー、9700
- Research Site
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Veszprem、ハンガリー、8200
- Research Site
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Helsinki、フィンランド、00029
- Research Site
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La Roche Sur Yon Cedex 9、フランス、85925
- Research Site
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Lyon、フランス、69008
- Research Site
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Marseille、フランス、13009
- Research Site
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Montpellier Cedex 5、フランス、34298
- Research Site
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Paris Cedex 20、フランス、75020
- Research Site
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Paris Cedex 5、フランス、75248
- Research Site
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Toulouse Cedex、フランス、31052
- Research Site
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Vandoeuvre les Nancy、フランス、54511
- Research Site
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Leuven、ベルギー、3000
- Research Site
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Liege、ベルギー、4000
- Research Site
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Wilrijk、ベルギー、2610
- Research Site
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Gdansk、ポーランド、80-952
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Lubin、ポーランド、59-300
- Research Site
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Poznan、ポーランド、61-485
- Research Site
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Warszawa、ポーランド、02-781
- Research Site
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Warszawa、ポーランド、04-141
- Research Site
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Wroclaw、ポーランド、53-413
- Research Site
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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:
- Subjects must have histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease. Locally recurrent disease must not be amenable to resection with curative intent.
- Measurable or non-measurable disease per modified RECIST guidelines
- ECOG of 0 or 1 (within 14 days prior to randomization)
Adequate organ and hematological function as evidenced by the following laboratory studies within 14 days prior to randomization:
• Cardiac function, as follows:
- Normal sinus rhythm (no significant ECG changes)
- Left ventricular ejection fraction ≥ LLN, as determined by echocardiogram or MUGA scan, according to institutional standards within 28 days prior to randomization
Exclusion Criteria:
- Inflammatory Breast Cancer
- Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 peripheral neuropathy > grade 1 at randomization
- History of arterial or venous thrombosis, including transient ischemic attack (TIA), within 1 year prior to randomization
- Adjuvant or neoadjuvant taxane treatment within 12 months of randomization. Any other adjuvant chemotherapy regimen must be discontinued at least 21 days prior to randomization
- Prior chemotherapy, vaccine, or biological therapy for locally recurrent or metastatic breast cancer (prior endocrine therapy is permitted)
- Prior radiation therapy, radiofrequency ablation, percutaneous cryotherapy or hepatic chemoembolization on all sites of disease unless disease progression was subsequently documented 14 days prior to randomization.
- Overexpression of HER-2 (gene amplification by FISH or 3+ over expression by immunohistochemistry).
- Current or prior history of central nervous system metastasis
- History of bleeding diathesis or clinically significant bleeding within 6 months prior to randomization
- Major surgical procedure within 28 days prior to randomization
- Open breast biopsy within 14 days prior to randomization
- Minor surgical procedure, placement of access device, or fine needle aspiration within 7 days of first dose
- Prior malignancy (other than thyroid cancer, in situ cervical cancer, or basal cell cancer of the skin, treated with curative intent and without evidence of disease for ≥ 3 years prior to randomization)
- Clinically significant cardiac disease within 12 months prior to randomization, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication
- Non-healing wound, ulcer or fracture
- Known hypersensitivity to paclitaxel or drugs using the vehicle cremophor
- Known hypersensitivity to bacterial proteins, or any of the drugs required in this study
- Known positive test for human immunodeficiency virus (HIV), hepatitis C, or hepatitis B surface antigen
- Known active or chronic hepatitis
- Uncontrolled hypertension as defined as systolic blood pressure ≥ 150 mm Hg and diastolic blood pressure ≥ 90 mm Hg. Anti-hypertensive medications are allowed if the subject is stable on their current dose at the time of randomization
- Currently or previously treated with any VEGF or VEGFr inhibitor, including but not limited to, bevacizumab, SU11248 (sunitinib), PTK787 (vatalinib), AZD 2171, AEE-788, BAY 43-9006 (sorafenib) and AMG 706.
- Treatment with coumarin-type anticoagulants, (other than low dose prophylaxis for central venous catheters ≤ 1mg/day) within 7 days prior to randomization
- Currently or previously treated with angiopoietin inhibitors, or inhibitors of TIE-1 or TIE-2 including, but not limited to, AMG 386, XL880, XL820
- Treatment with immune modulators such as cyclosporine and tacrolimus within 30 days prior to randomization
- Concomitant therapy with any hormonal agent such as raloxifene, tamoxifen, or other selective estrogen receptor modulators (SERMS), given for breast cancer prevention or for osteoporosis. Subjects must have discontinued these agents 28 days prior to randomization
- Pregnant (ie, positive beta-human chorionic gonadotropin test) or is breast feeding
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：ランダム化
- 介入モデル：並列代入
- マスキング：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：A
Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 10 mg/kg IV QW
|
AMG 386 3mg/kg IV QW [blinded]
Bevacizumab 10mg/kg IV Q2W
AMG 386 10mg/kg IV QW [Open-Label]
AMG 386 10mg/kg IV QW [blinded]
Paclitaxel 90mg/m2 IV QW (3 on/1 0ff)
|
|
実験的：D
Paclitaxel 90 mg/m² IV QW (3 on/1 off) + Open Label AMG 386 10 mg/kg IV QW
|
AMG 386 3mg/kg IV QW [blinded]
AMG 386 10mg/kg IV QW [Open-Label]
AMG 386 10mg/kg IV QW [blinded]
Paclitaxel 90mg/m2 IV QW (3 on/1 0ff)
|
|
実験的：B
Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 3 mg/kg IV QW
|
AMG 386 3mg/kg IV QW [blinded]
Bevacizumab 10mg/kg IV Q2W
AMG 386 10mg/kg IV QW [Open-Label]
AMG 386 10mg/kg IV QW [blinded]
Paclitaxel 90mg/m2 IV QW (3 on/1 0ff)
|
|
アクティブコンパレータ：C
Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 placebo IV QW
|
Bevacizumab 10mg/kg IV Q2W
Paclitaxel 90mg/m2 IV QW (3 on/1 0ff)
AMG 386 Placebo [blinded]
|
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 |
|---|---|
|
Progression-free survival (PFS)
時間枠：3 YEARS
|
3 YEARS
|
二次結果の測定
結果測定 |
時間枠 |
|---|---|
|
Objective Response (OR)
時間枠：3 YEARS
|
3 YEARS
|
|
Duration of Response (DOR)
時間枠：3 YEARS
|
3 YEARS
|
|
Time to response
時間枠：3 YEARS
|
3 YEARS
|
|
Overall Survival
時間枠：3 YEARS
|
3 YEARS
|
|
Time to progression (TTP)
時間枠：3 YEARS
|
3 YEARS
|
|
Incidence of AEs and significant laboratory changes
時間枠：3 YEARS
|
3 YEARS
|
|
AMG 386 Pharmakokinetic parameters
時間枠：3 YEARS
|
3 YEARS
|
|
Incidence of the occurrence of anti-AMG 386 antibody formation
時間枠：3 YEARS
|
3 YEARS
|
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
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- 20060341
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。
AMG 386の臨床試験
-
Amgen完了がん | 癌 | 卵巣がん | 卵管がん | 固形腫瘍 | 腫瘍学 | 腫瘍 | 転移 | 婦人科悪性腫瘍ベルギー, アメリカ, オーストラリア
-
National Cancer Institute (NCI)完了
-
Amgen完了癌 | 乳がん | 乳房腫瘍 | 転移性がん | 乳房腫瘍 | 固形腫瘍 | 腫瘍学 | 腫瘍 | 転移 | 局所再発および転移性乳がんアメリカ, ベルギー, フランス
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National Cancer Institute (NCI)完了
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Amgen完了卵巣がん | 卵管がん | 原発性腹膜がんアメリカ, フランス, イタリア, スペイン, イギリス, ベルギー, カナダ, ポーランド, スイス, 大韓民国, ロシア連邦, 香港, ポルトガル, 南アフリカ, イスラエル, ルーマニア, ブルガリア, ギリシャ, オーストラリア, スウェーデン, 日本, ラトビア, エストニア, インド, ブラジル, チリ, クロアチア, チェコ共和国, マレーシア, メキシコ, ペルー, スロベニア
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Chong Kun Dang Pharmaceutical完了
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Chong Kun Dang Pharmaceutical完了