Nab-Paclitaxel and Bevacizumab Followed By Bevacizumab and Erlotinib in Metastatic Breast Cancer
2018년 11월 6일 업데이트: Jennifer Specht, University of Washington
Combined Targeted Therapies for Triple Negative Advanced Breast Cancer - A Phase II Trial of Weekly Nab-Paclitaxel and Bevacizumab Followed by Maintenance Targeted Therapy With Bevacizumab and Erlotinib
This phase II trial studies how well giving paclitaxel albumin-stabilized nanoparticle (Nab-paclitaxel) formulation together with bevacizumab followed by bevacizumab and erlotinib hydrochloride work in treating patients with metastatic breast cancer.
Drugs used in chemotherapy, such as paclitaxel albumin-stabilized nanoparticle formulation, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.
Monoclonal antibodies, such as bevacizumab, can prevent cancer growth by blocking the ability of cancer cells to grow and spread.
Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
This trial evaluates a maintenance treatment with erlotinib and bevacizumab after Nab-paclitaxel and bevacizumab which may control cancer growth with biologic therapies.
연구 개요
상태
완전한
상세 설명
PRIMARY OBJECTIVES:
I. Progression free survival.
SECONDARY OBJECTIVES:
I. Response rate.
II. Overall survival.
III. Safety and toxicity.
IV. Exploratory biomarkers will be assessed as potential predictors of response to treatment including: expression of epidermal growth factor receptor (EGFR) and secreted protein acidic and rich in cysteine (SPARC) in the primary tumor and changes in levels of circulating tumor cells (CTCs) and circulating endothelial cells (CECs).
OUTLINE:
INDUCTION THERAPY: Patients receive paclitaxel albumin-stabilized nanoparticle formulation intravenously (IV) on days 1, 8, and 15 and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
MAINTENANCE THERAPY: Patients achieving complete response, partial response, or stable disease after completion of induction therapy will receive bevacizumab IV over 30-90 minutes once every 14 or 21 days and erlotinib hydrochloride orally (PO) once daily (QD) in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up per physician discretion.
연구 유형
중재적
등록 (실제)
59
단계
- 2 단계
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 장소
-
-
Alaska
-
Anchorage, Alaska, 미국, 99508
- Anchorage Oncology Centre
-
Anchorage, Alaska, 미국, 99508
- Katmai Oncology Group
-
Anchorage, Alaska, 미국, 99508
- Providence Alaska Medical Center
-
-
Arizona
-
Yuma, Arizona, 미국, 85364
- Yuma Cancer Center
-
-
Idaho
-
Lewiston, Idaho, 미국, 83501
- Saint Joseph Regional Medical Center
-
-
Montana
-
Bozeman, Montana, 미국, 59715
- Bozeman Deaconess Hospital
-
Kalispell, Montana, 미국, 59901
- Kalispell Regional Medical Center
-
-
Oregon
-
Bend, Oregon, 미국, 97701
- Bend Memorial Clinic
-
-
Washington
-
Kennewick, Washington, 미국, 99336
- Kadlec Clinic Hematology and Oncology
-
Kirkland, Washington, 미국, 98033
- Evergreen Hospital Medical Center
-
Mount Vernon, Washington, 미국, 98273
- Skagit Valley Hospital Regional Cancer Care Center
-
Redmond, Washington, 미국, 98052
- Group Health Cooperative, Redmond
-
Seattle, Washington, 미국, 98109
- Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
-
Sequim, Washington, 미국, 98384
- Olympic Medical Cancer Care Center
-
Spokane, Washington, 미국, 99208
- Spokane Valley Cancer Center-Mayfair
-
Tacoma, Washington, 미국, 98405
- Multicare Medical Oncology Hematology
-
Wenatchee, Washington, 미국, 98801
- Wenatchee Valley Medical Center
-
-
참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
- 어린이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
아니
연구 대상 성별
여성
설명
Inclusion Criteria:
- Have histologically confirmed invasive breast cancer that is estrogen receptor (ER) negative (=< 10%), progesterone receptor (PR) negative (=< 10%) and human epidermal growth factor receptor 2 (HER2) normal (=< 10% of cells) by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH)
- Be receiving first-line therapy for metastatic disease
- Measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST) criteria; X-rays, scans or physical examinations used for tumor measurement must have been completed within 28 days prior to registration; X-rays, scans or other tests for assessment of non-measurable disease must have been performed within 42 days prior to registration
- OR non-measurable disease only, with rising serum cancer antigen (CA)15-3 or CA 27.29 or carcinoembryonic antigen (CEA) documented by two consecutive measurements taken at least 14 days apart with the most recent measurement being within 42 days prior to registration; the second CA 15-3 or CA 27.29 or CEA value must have at least a 20% increase over the first and for CA 15-3 or CA 27.29 be greater than or equal to 40 units/mL or for CEA be greater than or equal to 4 ng/mL
- Subjects with brain metastases as their first site of disease recurrence may be eligible if treated by definitive radiation (stereotactic radiosurgery or whole brain) with clinically controlled neurologic symptoms for a period of 21 days prior to study treatment
- Bilirubin =< 1.5 mg/dL
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 X upper limit of normal, unless bone metastasis is present in the absence of liver metastasis
- Alkaline phosphatase =< 2.5 X upper limit of normal, unless bone metastasis is present in the absence of liver metastasis
- Platelets > 100,000 cells/mm^3
- Hemoglobin > 9.0 g/dL
- Absolute neutrophil count (ANC) >= 1,500 cells/mm^3
- Creatinine =< 1.5 mg/dL is recommended; however, institutional norms are acceptable
- If of childbearing potential must have a negative pregnancy test and use an effective method to avoid pregnancy for the duration of the trial and for at least 6 months after completion of study therapy
- Pre-existing peripheral neuropathy, if present, must be < grade 2 (per Common Terminology Criteria for Adverse Events [CTCAE] version 3.0)
- Patients must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional standards and federal guidelines
Exclusion Criteria:
- Recurrent disease within 12 months after completion of adjuvant chemotherapy containing a weekly taxane
- Central nervous system (CNS) metastases that are symptomatic and/or requiring steroids
- Pre-existing nephritic syndrome
- Serious intercurrent medical or psychiatric illness including serious active infection
- Inadequately controlled hypertension (defined as systolic blood pressure > 150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications)
- Any prior history of hypertensive crisis or hypertensive encephalopathy
- New York Heart Association (NYHA) grade II or greater congestive heart failure
- History of myocardial infarction or unstable angina within 6 months prior to study enrollment
- History of stroke or transient ischemic attack within 6 months prior to study enrollment
- Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
- Symptomatic peripheral vascular disease
- Evidence of bleeding diathesis or coagulopathy
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study
- Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
- Serious, non-healing wound, ulcer, or bone fracture
Proteinuria at screening as demonstrated by either:
- Urine protein:creatinine (UPC) ratio >= 1.0 at screening OR
- Urine dipstick for proteinuria > 2+ (patients discovered to have > 2+ proteinuria on dipstick urinalysis at baseline must have a UPC ratio done that is < 1.0 to be eligible; if the UPC ratio is >= 1.0 then the patient should undergo a 24-hour urine collection which must demonstrate =< 1 g of protein in 24 hours for the patient to be eligible)
- Known hypersensitivity to any component of bevacizumab or to nab-paclitaxel (paclitaxel albumin-stabilized nanoparticle formulation)
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
실험적: Tx (chemo, MoAb, and enzyme inhibitor)
INDUCTION THERAPY: Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV on days 1, 8, and 15 and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients achieving complete response, partial response, or stable disease after completion of induction therapy will receive bevacizumab IV over 30-90 minutes once every 14 or 21 days and erlotinib hydrochloride PO QD in the absence of disease progression or unacceptable toxicity. |
주어진 IV
다른 이름들:
주어진 PO
다른 이름들:
주어진 IV
다른 이름들:
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Progression-free Survival (PFS)
기간: Time from date of registration to date of first documentation of progression or symptomatic deterioration or death due to any cause, assessed up to 8 years
|
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.
Kaplan-Meier survival curves will be used.
A 95% confidence interval for the median PFS will be calculated.
A lower bound greater than 8 months would be strong evidence that Nab-Paclitaxel- bevacizumab induction therapy followed by bevacizumab-erlotinib hydrochloride maintenance therapy is superior to paclitaxel and bevacizumab.
However, a median PFS of 13 months or greater (regardless of whether the 95% confidence interval for the median extends below 8 months) could also indicate promising results.
|
Time from date of registration to date of first documentation of progression or symptomatic deterioration or death due to any cause, assessed up to 8 years
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Overall Survival
기간: Time from date of registration to date of death due to any cause, assessed up to 8 years
|
Kaplan-Meier survival curves will be used.
|
Time from date of registration to date of death due to any cause, assessed up to 8 years
|
|
Percentage of Participants With Response
기간: Up to 8 years
|
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) 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.
|
Up to 8 years
|
|
Incidence of Adverse Events as Assessed by National Cancer Institute CTCAE Version 3.0
기간: Up to 30 days after treatment discontinuation
|
Adverse events that meet severity grade 2 or greater will be collected and reported.
The number and percent of subjects reporting adverse events (all, severe or worse, serious and related) will be summarized for all patients, and stratified by center and other subgroups of interest.
|
Up to 30 days after treatment discontinuation
|
|
EGFR and SPARC Expression in the Primary Tumor
기간: Up to 8 years
|
Up to 8 years
|
|
|
Changes in Levels of Circulating Tumor Cells
기간: Baseline to up to 8 years
|
Descriptive statistics, such as mean, standard deviation, and range, will be summarized for circulating tumor cells at baseline and last visit.
|
Baseline to up to 8 years
|
|
Changes in Levels of Circulating Endothelial Cells
기간: Baseline to up to 8 years
|
Descriptive statistics, such as mean and standard deviation, will be summarized for circulating endothelial cells at baseline and last visit.
|
Baseline to up to 8 years
|
공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작 (실제)
2008년 4월 23일
기본 완료 (실제)
2017년 7월 5일
연구 완료 (실제)
2017년 9월 28일
연구 등록 날짜
최초 제출
2008년 8월 12일
QC 기준을 충족하는 최초 제출
2008년 8월 12일
처음 게시됨 (추정)
2008년 8월 13일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2018년 12월 4일
QC 기준을 충족하는 마지막 업데이트 제출
2018년 11월 6일
마지막으로 확인됨
2018년 11월 1일
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- 6628 (Fred Hutchinson Cancer Research Center/UW Consortium)
- P30CA015704 (미국 NIH 보조금/계약)
- NCI-2010-00041 (레지스트리 식별자: CTRP (Clinical Trial Reporting Program))
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. .