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.
연구 개요
상태
상세 설명
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.
연구 유형
등록 (실제)
단계
- 2 단계
연락처 및 위치
연구 장소
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Maastricht, 네덜란드, 6229 HX
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Herlev, 덴마크, 2730
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Arizona
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Litchfield Park, Arizona, 미국, 85340
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Tucson, Arizona, 미국, 85724
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Arkansas
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Hot Springs, Arkansas, 미국, 71913
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Little Rock, Arkansas, 미국, 72205
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California
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Campbell, California, 미국, 95008
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Los Angeles, California, 미국, 90095
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Murrieta, California, 미국, 92562
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Santa Maria, California, 미국, 93454
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Connecticut
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New Haven, Connecticut, 미국, 06520
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Stamford, Connecticut, 미국, 06902
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Florida
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Orlando, Florida, 미국, 32804
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Minnesota
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Robbinsdale, Minnesota, 미국, 55422
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Nevada
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Henderson, Nevada, 미국, 89052
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New Hampshire
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Lebanon, New Hampshire, 미국, 03756
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Nashua, New Hampshire, 미국, 03061
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New Jersey
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Edison, New Jersey, 미국, 08820
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Mountain Lakes, New Jersey, 미국, 07046
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North Carolina
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Asheville, North Carolina, 미국, 28806
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Charlotte, North Carolina, 미국, 28203
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Pennsylvania
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Hershey, Pennsylvania, 미국, 17033
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Philadelphia, Pennsylvania, 미국, 19106
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South Carolina
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Columbia, South Carolina, 미국, 29210
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Texas
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Richardson, Texas, 미국, 75080
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San Antonio, Texas, 미국, 78229
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Sugar Land, Texas, 미국, 77479
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Utah
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Ogden, Utah, 미국, 84403
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Leuven, 벨기에, 3000
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Liege, 벨기에, 4000
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Wilrijk, 벨기에, 2610
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Madrid, 스페인, 28033
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AndalucÃ-a
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Jaén, AndalucÃ-a, 스페인, 23007
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Cataluña
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Sabadell, Cataluña, 스페인, 08208
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Galicia
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Santiago de Compostela, Galicia, 스페인, 15706
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Guildford, 영국, GU2 7XX
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Leicester, 영국, LE1 5WW
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London, 영국, W6 8RF
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London, 영국, NW1 2PG
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Manchester, 영국, M20 4BX
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Northwood, 영국, HA6 2RN
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Nottingham, 영국, NG5 1PB
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Innsbruck, 오스트리아, 6020
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Wels, 오스트리아, 4600
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Wien, 오스트리아, 1090
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Karnataka
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Bangalore, Karnataka, 인도, 560 029
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Maharashtra
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Miraj, Maharashtra, 인도, 416 410
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Mumbai, Maharashtra, 인도, 400 012
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Nagpur, Maharashtra, 인도, 440 012
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Pune, Maharashtra, 인도, 411 001
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Rajasthan
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Jaipur, Rajasthan, 인도, 302 013
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Jaipur, Rajasthan, 인도, 302 004
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Gdansk, 폴란드, 80-952
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Lubin, 폴란드, 59-300
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Poznan, 폴란드, 61-485
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Warszawa, 폴란드, 02-781
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Warszawa, 폴란드, 04-141
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Wroclaw, 폴란드, 53-413
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La Roche Sur Yon Cedex 9, 프랑스, 85925
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Lyon, 프랑스, 69008
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Marseille, 프랑스, 13009
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Montpellier Cedex 5, 프랑스, 34298
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Paris Cedex 20, 프랑스, 75020
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Paris Cedex 5, 프랑스, 75248
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Toulouse Cedex, 프랑스, 31052
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Vandoeuvre les Nancy, 프랑스, 54511
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Helsinki, 핀란드, 00029
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Gyula, 헝가리, 5700
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Kaposvar, 헝가리, 7400
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Szombathely, 헝가리, 9700
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Veszprem, 헝가리, 8200
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South Australia
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Kurralta Park, South Australia, 호주, 5037
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Victoria
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Epping, Victoria, 호주, 3076
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Fitzroy, Victoria, 호주, 3065
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Footscray, Victoria, 호주, 3011
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Malvern, Victoria, 호주, 3144
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Western Australia
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Perth, Western Australia, 호주, 6000
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
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
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 네 배로
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
실험적: A
Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 10 mg/kg IV QW
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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)
|
|
실험적: D
Paclitaxel 90 mg/m² IV QW (3 on/1 off) + Open Label AMG 386 10 mg/kg IV QW
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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)
|
|
실험적: 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)
|
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활성 비교기: C
Paclitaxel 90 mg/m² IV QW (3 on/1 off) + bevacizumab 10 mg/kg IV Q2W + AMG 386 placebo IV QW
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Bevacizumab 10mg/kg IV Q2W
Paclitaxel 90mg/m2 IV QW (3 on/1 0ff)
AMG 386 Placebo [blinded]
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
기간 |
|---|---|
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Progression-free survival (PFS)
기간: 3 YEARS
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3 YEARS
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2차 결과 측정
결과 측정 |
기간 |
|---|---|
|
Objective Response (OR)
기간: 3 YEARS
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3 YEARS
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Duration of Response (DOR)
기간: 3 YEARS
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3 YEARS
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Time to response
기간: 3 YEARS
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3 YEARS
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Overall Survival
기간: 3 YEARS
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3 YEARS
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Time to progression (TTP)
기간: 3 YEARS
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3 YEARS
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Incidence of AEs and significant laboratory changes
기간: 3 YEARS
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3 YEARS
|
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AMG 386 Pharmakokinetic parameters
기간: 3 YEARS
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3 YEARS
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Incidence of the occurrence of anti-AMG 386 antibody formation
기간: 3 YEARS
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3 YEARS
|
공동 작업자 및 조사자
스폰서
간행물 및 유용한 링크
연구 기록 날짜
연구 주요 날짜
연구 시작
기본 완료 (실제)
연구 완료 (실제)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (추정)
연구 기록 업데이트
마지막 업데이트 게시됨 (추정)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
키워드
추가 관련 MeSH 약관
기타 연구 ID 번호
- 20060341
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .
AMG 386에 대한 임상 시험
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Amgen완전한암종 | 암 | 난소 암 | 나팔관암 | 고형 종양 | 종양학 | 종양 | 전이 | 부인과 악성종양벨기에, 미국, 호주
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National Cancer Institute (NCI)완전한
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Amgen완전한암 | 유방암 | 유방 신생물 | 전이성 암 | 유방 종양 | 고형 종양 | 종양학 | 종양 | 전이 | 국소 재발성 및 전이성 유방암미국, 벨기에, 프랑스
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Chong Kun Dang Pharmaceutical알려지지 않은
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National Cancer Institute (NCI)완전한
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Amgen완전한난소 암 | 나팔관암 | 원발성 복막암미국, 프랑스, 이탈리아, 스페인, 영국, 벨기에, 캐나다, 폴란드, 스위스, 대한민국, 러시아 연방, 홍콩, 포르투갈, 남아프리카, 이스라엘, 루마니아, 불가리아, 그리스, 호주, 스웨덴, 일본, 라트비아, 에스토니아, 인도, 브라질, 칠레, 크로아티아, 체코 공화국, 말레이시아, 멕시코, 페루, 슬로베니아