- ICH GCP
- 미국 임상 시험 레지스트리
- 임상시험 NCT00915603
Trial of Paclitaxel/Bevacizumab +/- Everolimus for Patients With HER2-Negative Metastatic Breast Cancer
A Randomized, Double-Blind, Placebo-Controlled Phase II Trial of Weekly Paclitaxel/Bevacizumab +/- Everolimus as First-Line Chemotherapy for Patients With HER2-Negative Metastatic Breast Cancer (MBC)
This randomized, double blind, placebo controlled trial will evaluate the impact of adding everolimus to the combination of weekly paclitaxel plus bevacizumab in the first-line treatment of women with HER2-negative metastatic breast cancer. Patients will be randomized (1:1) to receive either paclitaxel/bevacizumab/everolimus (Treatment Arm 1) or paclitaxel/ bevacizumab/placebo (Treatment Arm 2). Patients will be evaluated for response to treatment every 8 weeks; responding and/or stable patients will continue treatment, with re-evaluations every 8 weeks, until tumor progression or
intolerable toxicity occurs. Outcomes will be assessed for each treatment arm
separately. This trial is not intended to compare treatment arms primarily. Any such analyses are exploratory and will be conducted without adjustment for multiple hypothesis testing.
연구 개요
상태
정황
연구 유형
등록 (실제)
단계
- 2 단계
연락처 및 위치
연구 장소
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California
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LaVerne, California, 미국, 91750
- Wilshire Oncology Medical Group
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Connecticut
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Norwich, Connecticut, 미국, 06360
- Eastern Connecticut Hematology Oncology
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Florida
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Aventura, Florida, 미국, 33180
- Aventura Medical Center
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Fort Myers, Florida, 미국, 33901
- Florida Cancer Specialists
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Maine
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Portland, Maine, 미국, 04101
- Mercy Hospital
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Maryland
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Bethesda, Maryland, 미국, 20817
- Center for Cancer and Blood Disorders
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Bethesda, Maryland, 미국, 20817
- National Capital Clinical Research Associates
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Ohio
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Cincinnati, Ohio, 미국, 45242
- Oncology Hematology Care
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Columbus, Ohio, 미국, 43219
- Mid Ohio Oncology/Hematology, Inc./ The Mark H. Zangmeister Center
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South Carolina
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Columbia, South Carolina, 미국, 29210
- South Carolina Oncology Associates, PA
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Tennessee
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Chattanooga, Tennessee, 미국, 37404
- Chattanooga Oncology Hematology Associates
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Nashville, Tennessee, 미국, 37023
- Tennessee Oncology, PLLC
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Texas
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Dallas, Texas, 미국, 75246
- Texas Oncology
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Virginia
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Fairfax, Virginia, 미국, 22031
- Fairfax Northern Virginia Hem-Onc
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Richmond, Virginia, 미국, 23235
- Virginia Cancer Institute
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
- Female or male patients >=18 years of age.
- Histologically confirmed invasive breast cancer, locally unresectable or metastatic.
No prior chemotherapy for MBC. Patients may have received adjuvant or
neoadjuvant chemotherapy (including taxanes and/or bevacizumab) as long as
treated was completed >12 months prior to relapse. Prior hormonal therapy in the
adjuvant or metastatic setting will be permitted.
- Prior hormonal therapy in the adjuvant or metastatic setting is permitted. Estrogen receptor positive patients should be considered candidates for chemotherapy.
HER2-negative breast cancer, defined as follows:
- FISH-negative (FISH ratio <2.2), or
- IHC 0-1+, or
- IHC 2-3+ AND FISH-negative (FISH ratio <2.2).
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
Adequate hematologic function, defined by:
· Absolute neutrophil count (ANC) >1500/mm3
- Platelet count >=100,000/mm3
- Hemoglobin >9 g/dL
Adequate liver function, defined by:
· AST and ALT <=2.5 x the upper limit of normal (ULN) or <=5 x ULN in
presence of liver metastases
- Total bilirubin <=1.5 x ULN
Adequate renal function, defined by:
· Serum creatinine <=1.5 x ULN or calculated creatinine clearance of
>=40 ml/min
International normalized ratio (INR) <=1.5 or prothrombin time (PT)/partial
thromboplastin time (PTT) within normal limits (WNL) of the institution (if patient is not on anti-coagulation therapy). Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin are eligible if the INR is stable and within the therapeutic range prior to study treatment initiation.
- Adequate lipid profile: total cholesterol <=300 mg/dL OR <=7.75 mmol/L and fasting triglyceride 2.5 x ULN. Note: In case one or both of these thresholds are exceeded,the patient can only be included after initiation of appropriate lipid lowering medication.
Patients with proteinuria at screening as demonstrated by either:
· Urine protein creatinine (UPC) ration >1.0 at screening
or
- Urine dipstick for proteinuria >=2+ (patients discovered to have
>=2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour
urine collection and must demonstrate <1 g of protein in 24 hours to be
eligible).
- Measurable disease by RECIST criteria.
- Life expectancy >=12 weeks.
- Ability to swallow oral medications.
Adequate cardiac function, defined by baseline left ventricular ejection fraction (LVEF) value >= normal per institutional guidelines by MUGA scan or
echocardiogram (ECHO).
Adequate recovery from recent surgery.
- Major surgical procedure >28 days from study entry
- Minor surgical procedure >7 days from study entry (Portacath placement
excepted - patients can start treatment <7 days after portacath placement.)
- Patients with previous history of invasive cancers (including breast cancer) are eligible if definitive treatment was completed more than 5 years prior to initiating current study treatment, and there is no evidence of recurrent disease.
- Patient must be accessible for treatment and follow-up.
All patients must be able to understand the investigational nature of the study and give written informed consent prior to study entry.
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Exclusion Criteria:
- Patients with active brain metastases or meningeal metastases. Patients who have had brain metastases resected, or have received brain radiation therapy >4 weeks prior to study entry are eligible, if they meet all of the following criteria: 1) residual symptoms < grade 2, 2) no dexamethasone requirement, and 3) follow-up MRI shows regression of lesions after treatment and no new lesions appearing.
Previous treatment with an m-TOR inhibitor (sirolimus, temsirolimus, everolimus) or anti-angiogenesis agent unless:
- in the adjuvant setting, and
- >=12 months prior to recurrence.
- Previous radiotherapy for metastatic disease completed <2 weeks prior to study treatment initiation.
Patients who are current receiving systemic cancer therapy or have received
previous systemic therapy within 4 weeks of the start of study drug (e.g.
chemotherapy, antibody therapy, targeted agents).
- Women who are pregnant or lactating. All patients with reproductive potential must agree to use effective contraception from time of study entry until at least 3 months after the last administration of study drug.
Uncontrolled hypertension defined as systolic blood pressure >150 mmHg or
diastolic pressure >100 mmHg, despite optimal medical management.
- Concurrent use of CYP3A4 inhibitors and inducers from 72 hours prior to initiation of study treatment until the end of treatment with everolimus.
- Cardiac disease, including: congestive heart failure (CHF) > Class II per New York Heart Association (NYHA) classification; unstable angina (anginal symptoms at rest) or new-onset angina (i.e., began within the last 3 months), or myocardial infarction within the past 6 months; symptomatic CHF, unstable angina pectoris, or cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
History of stroke or transient ischemic attack within 6 months prior to first
bevacizumab dose.
- Patients with any non-healing wound, ulcer, or long-bone fracture.
- Patients with clinical history of hemoptysis or hematemesis.
- Patients with any history of a bleeding diathesis or coagulopathy.
- Patients with a PEG or G tube cannot be enrolled into this trial.
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to beginning bevacizumab.
- Patients with an impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
Patients who have any severe and/or uncontrolled medical conditions or other
conditions that could affect their participation such as:
- severe impaired lung functions as defined as spirometry and DLCO that is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air
- uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN.
- History of any other disease, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug, or that might affect interpretation of the results of this study, or render the subject at high risk for treatment complications.
- History of hypersensitivity to Cremophor EL (polyoxyethylated castor oil) or a drug formulated in Cremophor EL, such as paclitaxel.
- Patients may not receive any other investigational or anti-cancer treatments while participating in this study.
- Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent. Topical or inhaled corticosteroids are allowed.
- Patients should not receive immunization with attenuated live vaccines within one week of study entry or during study period.
- Concurrent severe, uncontrolled infection or intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.
- Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus) or its excipients.
Patients with a known HIV seropositivity.
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공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 삼루타
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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활성 비교기: paclitaxel/bevacizumab/everolimus
Systemic Therapy
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Everolimus 10mg PO daily continuously for all 28 days of a cycle
다른 이름들:
Bevacizumab 10mg/kg IV Days 1 and 15 of 28 day cycle
다른 이름들:
Paclitaxel 90mg/m2 1-hour IV infusion Days 1, 8 and 15 of 28 day cycle.
Patients will receive standard pre-medication before each paclitaxel treatment to prevent a hypersensitivity reaction.
다른 이름들:
Bevacizumab 10mg/kg IV days 1 and 15 of 28 day cycle
다른 이름들:
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위약 비교기: paclitaxel/bevacizumab/placebo
Systemic Therapy
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Bevacizumab 10mg/kg IV Days 1 and 15 of 28 day cycle
다른 이름들:
Paclitaxel 90mg/m2 1-hour IV infusion Days 1, 8 and 15 of 28 day cycle.
Patients will receive standard pre-medication before each paclitaxel treatment to prevent a hypersensitivity reaction.
다른 이름들:
Bevacizumab 10mg/kg IV days 1 and 15 of 28 day cycle
다른 이름들:
Placebo PO daily continuously for all 28 days of a cycle
다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
---|---|---|
Progression-Free Survival (PFS)
기간: every 8 weeks until progressive disease, expected average of 18 months
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Progression-free survival will be measured from Day 1 of study drug administration to disease progression defined by Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1) 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
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every 8 weeks until progressive disease, expected average of 18 months
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
---|---|---|
Number of Patients With Treatment-related Adverse Events (AEs) as a Measure of Safety and Tolerability
기간: every 4 weeks until intolerable toxicity occurs
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Assessments will be made based on the analysis of reported incidence of treatment-emergent AEs
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every 4 weeks until intolerable toxicity occurs
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Overall Response Rate (ORR)
기간: every 8 weeks until treatment discontinuation, expected average of 18 months
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The number of patients with observed complete response [CR] or partial response [PR].
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by 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
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every 8 weeks until treatment discontinuation, expected average of 18 months
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Duration of Response (DOR)
기간: every 8 weeks until treatment discontinuation, expected average 6 months
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Defined as time between date of objective response and date of response to disease progression or death, as defined by RECIST v1.1 criteria.
Objective response is defined as either complete response [CR] or partial response [PR].
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions.
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), 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
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every 8 weeks until treatment discontinuation, expected average 6 months
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Overall Survival (OS)
기간: every 8 weeks until treatment discontinuation, expected average 6 months
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Assessed from Day 1 of study drug administration to date of death due to any cause.
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every 8 weeks until treatment discontinuation, expected average 6 months
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공동 작업자 및 조사자
협력자
수사관
- 연구 의자: Denise A. Yardley, M.D., SCRI Development Innovations, LLC
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 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. .
전이성 유방암에 대한 임상 시험
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Georgetown UniversityNational Cancer Institute (NCI); American Cancer Society, Inc.; Susan G. Komen Breast Cancer...완전한
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University of UtahNational Cancer Institute (NCI)모병피로 | 좌식 생활 | 전이성 전립선암 | IV기 전립선암 AJCC(American Joint Committee on Cancer) v8 | IVA기 전립선암 AJCC(American Joint Committee on Cancer) v8 | IVB기 전립선암 AJCC(American Joint Committee on Cancer) v8미국
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Jonsson Comprehensive Cancer Center아직 모집하지 않음전립선암 | IVB기 전립선암 American Joint Committee on Cancer(AJCC) v8미국
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Rashmi Verma, MDNational Cancer Institute (NCI)모병거세저항성 전립선암 | 전이성 전립선 선암종 | IVB기 전립선암 American Joint Committee on Cancer(AJCC) v8미국
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Jonsson Comprehensive Cancer Center빼는전립선 선암종 | 2기 전립선암 AJCC v8 | IIC기 전립선암 AJCC v8 | IIA기 전립선암 AJCC v8 | IIB기 전립선암 AJCC v8 | 1기 전립선암 American Joint Committee on Cancer(AJCC) v8미국
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Jonsson Comprehensive Cancer CenterMiraDX모집하지 않고 적극적으로전립선 선암종 | 2기 전립선암 AJCC v8 | IIC기 전립선암 AJCC v8 | IIA기 전립선암 AJCC v8 | IIB기 전립선암 AJCC v8 | 1기 전립선암 American Joint Committee on Cancer(AJCC) v8미국
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Jonsson Comprehensive Cancer Center종료됨거세저항성 전립선암 | 전이성 전립선암 | IVA기 전립선암 AJCC v8 | IVB기 전립선암 AJCC v8 | IV기 전립선암 American Joint Committee on Cancer(AJCC) v8미국
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Jonsson Comprehensive Cancer CenterProgenics Pharmaceuticals, Inc.종료됨2기 전립선암 AJCC v8 | IIIA기 전립선암 AJCC v8 | IIIB기 전립선암 AJCC v8 | IIC기 전립선암 AJCC v8 | 3기 전립선암 AJCC v8 | IIIC기 전립선암 AJCC v8 | IIA기 전립선암 AJCC v8 | IIB기 전립선암 AJCC v8 | 1기 전립선암 American Joint Committee on Cancer(AJCC) v8미국
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Jonsson Comprehensive Cancer Center종료됨생화학적으로 재발하는 전립선암 | 전이성 전립선암 | 뼈의 전이성 악성 신생물 | IVA기 전립선암 AJCC v8 | IVB기 전립선암 AJCC v8 | IV기 전립선암 American Joint Committee on Cancer(AJCC) v8미국
Everolimus에 대한 임상 시험
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Novartis Pharmaceuticals완전한
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Yonsei University알려지지 않은
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Abbott Medical Devices완전한관상동맥 질환 | 관상 동맥 질환 | 관상동맥 재협착아일랜드, 네덜란드, 싱가포르, 스페인, 중국, 벨기에, 스위스, 태국, 이스라엘, 독일, 뉴질랜드, 영국, 이탈리아, 말레이시아, 캐나다, 인도, 오스트리아, 프랑스, 남아프리카, 포르투갈, 체코 공화국, 그리스, 스웨덴
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Yonsei University알려지지 않은
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Ajou University School of Medicine알려지지 않은