Entinostat, Lapatinib Ditosylate and Trastuzumab in Treating Patients With Locally Recurrent or Distant Relapsed Metastatic Breast Cancer Previously Treated With Trastuzumab Only
2019년 5월 17일 업데이트: National Cancer Institute (NCI)
Phase I and Phase I Trastuzumab Cohort Study of Entinostat, Lapatinib and Trastuzumab in Patients With HER2-Positive Metastatic Breast Cancer in Whom Trastuzumab Has Failed
This phase I trial studies the side effects and best dose of entinostat when given together with lapatinib ditosylate and trastuzumab in treating patients with breast cancer that has spread from the original (primary) tumor to distant organs or distant lymph nodes or has recurred (come back) at or near the same place as the original (primary) tumor, usually after a period of time during which the cancer could not be detected.
Entinostat and lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Monoclonal antibodies, such as trastuzumab, may interfere with the ability of tumor cells to grow and spread.
Giving entinostat together with lapatinib ditosylate and trastuzumab may kill more tumor cells.
연구 개요
상태
완전한
상세 설명
PRIMARY OBJECTIVES:
I. To determine the recommended phase II dose (RP2D) for entinostat in combination with lapatinib (lapatinib ditosylate) in patients whom trastuzumab has failed for human epidermal growth factor receptor 2+ (HER2+) metastatic breast cancer (Phase I).
II. To determine the maximum tolerated dose (MTD) for entinostat in combination with lapatinib and trastuzumab in patients whom trastuzumab has failed for HER2+ metastatic breast cancer (Phase I Trastuzumab Cohort).
SECONDARY OBJECTIVES:
I. To determine the toxicity of combination therapy with entinostat and lapatinib in patients whom trastuzumab has failed for HER2+ metastatic breast cancer (Phase I).
II. To determine the toxicity of entinostat in combination with lapatinib and trastuzumab in patients whom trastuzumab has failed for HER2+ metastatic breast cancer (Phase I Trastuzumab Cohort).
EXPLORATORY OBJECTIVES:
I. Determine whether the 2-drug combination modulates the expression of HER2, phosphorylated HER2 (pHER), epidermal growth factor receptor (EGFR), phosphorylated EGFR (pEGFR), v-akt murine thymoma viral oncogene homolog 1 (Akt), and phosphorylated Akt (pAkt) in breast tumors and/or circulating tumor cells (CTCs).
OUTLINE: This is a dose-escalation study of entinostat.
Patients receive entinostat orally (PO) on days 1 and 15 and lapatinib tosylate PO on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients in the Phase I trastuzumab cohort also receive maintenance dose of trastuzumab intravenously (IV) over 30-90 minutes every 3 weeks.
After completion of study treatment, patients are followed up for 28 days or until toxicities are resolved.
연구 유형
중재적
등록 (실제)
37
단계
- 1단계
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 장소
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Texas
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Houston, Texas, 미국, 77030
- M D Anderson Cancer Center
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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
18년 이상 (성인, 고령자)
건강한 자원 봉사자를 받아들입니다
아니
연구 대상 성별
모두
설명
Inclusion Criteria:
- Patients have histological confirmation of invasive breast carcinoma
- Patients have locally recurrent or distant relapsed metastatic disease
- Patients have positive HER2 expression by immunohistochemistry (IHC) (3+) or fluorescence in situ hybridization (FISH) testing (> 2.0 ratio)
- Patients are able to swallow and retain oral medication (i.e., no uncontrolled vomiting, inability to swallow, or diagnosis of chronic malabsorption)
- Patients have Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Patients must have received prior trastuzumab for > 2 month period before disease recurrence or recurrence or progression while on trastuzumab-based therapy
- Patients have ability and willingness to sign written informed consent
- Female patients of childbearing potential (a female not free from menses > 2 years or not surgically sterilized) must be willing to use an adequate barrier method of contraception to prevent pregnancy or agree to abstain from heterosexual activity throughout the study; male patients who are able to father children must use an adequate barrier method of contraception
- Female patients of childbearing potential must have negative serum pregnancy test within 14 days of starting protocol therapy
- Patients with brain metastasis have no signs of progressive disease 4 months after the completion of brain metastasis treatment (radiation therapy, surgery, etc.) do not require anticonvulsants or corticosteroids, and have been off such drugs for at least 7 days
- Both men and women and members of all races and ethnic groups are eligible for this trial
Exclusion Criteria:
- Patients are receiving concurrent anti-cancer therapy (chemotherapy, immunotherapy, biological therapy and hormonal therapy) while taking study medication
- Serum bilirubin >= 1.5 x upper limit of normal (ULN)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >= 3 x ULN (with or without liver metastasis [mets])
- Absolute neutrophil count (ANC) < 1.5
- Hemoglobin =< 9
- Platelet =< 140,000
- Patients have an active infection and require intravenous (IV) or oral antibiotics
- Cardiac arrhythmia requiring maintenance medication
- History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug
- Patients have a concurrent disease or condition that would make them inappropriate for study participation, or any serious medical disorder that would interfere with patients' safety
- Serum creatinine > 2.0 mg/dL
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 |
|---|---|
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실험적: Treatment (entinostat, lapatinib ditosylate and trastuzumab)
Patients receive entinostat PO on days 1 and 15 and lapatinib tosylate PO on days 1-28.
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients in the Phase I Trastuzumab Cohort also receive maintenance dose of trastuzumab IV over 30-90 minutes every 3 weeks.
|
상관 연구
주어진 IV
다른 이름들:
주어진 PO
다른 이름들:
주어진 PO
다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
기간 |
|---|---|
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RP2D for entinostat in combination with lapatinib ditosylate defined as the highest dose level in which 6 patients have been treated with at most 1 patient experiencing dose limiting toxicity
기간: Up to 28 days
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Up to 28 days
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2차 결과 측정
결과 측정 |
기간 |
|---|---|
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Incidence of grade III or IV toxicities, graded according to Common Terminology Criteria for Adverse Events version 4
기간: Up to 28 days
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Up to 28 days
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기타 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Changes in CTCs levels before and after the combination treatment of entinostat, lapatinib ditosylate and trastuzumab
기간: Baseline up to 28 days after completion of study treatment
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Summary statistics (mean, standard deviation, median, quartiles) will be summarized for these changes in CTCs and biomarkers by patient tumor response status (yes vs. no).
Changes will be compared between the two groups of patients (yes vs. no tumor response) using the two-sample t-test.
If the data is skewed, Wilcoxon rank-sum test will be used.
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Baseline up to 28 days after completion of study treatment
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Changes in phosphorylated Akt levels before and after the combination treatment of entinostat, lapatinib ditosylate and trastuzumab.
기간: Baseline up to 28 days after completion of study treatment
|
Summary statistics (mean, standard deviation, median, quartiles) will be summarized for these changes in CTCs and biomarkers by patient tumor response status (yes vs. no).
Changes will be compared between the two groups of patients (yes vs. no tumor response) using the two-sample t-test.
If the data is skewed, Wilcoxon rank-sum test will be used.
|
Baseline up to 28 days after completion of study treatment
|
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Changes in phosphorylated HER2 levels before and after the combination treatment of entinostat, lapatinib ditosylate and trastuzumab
기간: Baseline up to 28 days after completion of study treatment
|
Summary statistics (mean, standard deviation, median, quartiles) will be summarized for these changes biomarkers by patient tumor response status (yes vs. no).
Changes will be compared between the two groups of patients (yes vs. no tumor response) using the two-sample t-test.
If the data is skewed, Wilcoxon rank-sum test will be used.
|
Baseline up to 28 days after completion of study treatment
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Changes in phosphorylated EGFR levels before and after the combination treatment of entinostat, lapatinib ditosylate and trastuzumab
기간: Baseline up to 28 days after completion of study treatment
|
Summary statistics (mean, standard deviation, median, quartiles) will be summarized for these changes biomarkers by patient tumor response status (yes vs. no).
Changes will be compared between the two groups of patients (yes vs. no tumor response) using the two-sample t-test.
If the data is skewed, Wilcoxon rank-sum test will be used.
|
Baseline up to 28 days after completion of study treatment
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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)
2012년 1월 10일
기본 완료 (실제)
2016년 2월 16일
연구 완료 (실제)
2016년 2월 16일
연구 등록 날짜
최초 제출
2011년 9월 13일
QC 기준을 충족하는 최초 제출
2011년 9월 13일
처음 게시됨 (추정)
2011년 9월 14일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2019년 5월 20일
QC 기준을 충족하는 마지막 업데이트 제출
2019년 5월 17일
마지막으로 확인됨
2019년 5월 1일
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- NCI-2011-03222 (레지스트리 식별자: CTRP (Clinical Trial Reporting Program))
- P30CA016672 (미국 NIH 보조금/계약)
- UM1CA186688 (미국 NIH 보조금/계약)
- U01CA062461 (미국 NIH 보조금/계약)
- 8871 (기타 식별자: CTEP)
- NCI 8871
- 2010-0842 (기타 식별자: M D Anderson Cancer Center)
- CDR0000710891
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