Docetaxel, Cisplatin, Irinotecan and Bevacizumab (TPCA) in Metastatic Esophageal and Gastric Cancer
2017년 7월 5일 업데이트: Peter C. Enzinger, MD, Dana-Farber Cancer Institute
A Phase II Trial of Docetaxel, Cisplatin, Irinotecan and Bevacizumab (TPCA) in Metastatic Esophageal and Gastric Cancer
The purpose of this research study is to determine if the combination of docetaxel, cisplatin, irinotecan and bevacizumab will help shrink metastatic esophageal or gastric cancer and how the cancer responds to this combination.
Bevacizumab is a new drug that is believed to stop the formation of new blood vessels that carry nutrients to tumors.
Bevacizumab is approved for use in metastatic colon and rectal cancer.
Docetaxel, cisplatin and irinotecan are traditional chemotherapy agents that have been tested together in another clinical trial for esophageal and gastric cancer.
It is hoped that adding bevacizumab to this regimen will make the treatment more effective.
연구 개요
상세 설명
OBJECTIVES:
Primary
To determine the 10-month progression-free survival rate for the combination of TPC and Bevacizumab in patients with metastatic esophageal or gastric cancer
Secondary
- To determine the response rate (RECIST) and median duration of response
- To determine overall survival
- To determine toxicity
Exploratory
- To explore if 7/7 and 7/6 UGT1A1 polymorphisms correlate with grade III/IV irinotecan-related diarrhea and neutropenia when irinotecan is given at relatively low dose to patients with esophageal and gastric cancer
- To correlate expression of tumoral and serum VEGF with response and survival
- To correlate TGF alpha levels and tumor microvessel density with clinical activity
- To examine circulating endothelial cells (CECs) as surrogate markers of antitumor activity of bevacizumab
DESIGN This trial will use a single stage design to differentiate a >/= 50% rate of 10-month progression-free survival from a </= 30% rate. The proposed regimen would be promising if at least 15 of 35 patients were alive and progression-free at 10 months.
연구 유형
중재적
등록 (실제)
38
단계
- 2 단계
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 장소
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Massachusetts
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Boston, Massachusetts, 미국, 02115
- Dana-Farber Cancer Institute
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Boston, Massachusetts, 미국, 02114
- Massachusetts General Hospital
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Boston, Massachusetts, 미국, 02115
- Beth Israel Deaconess Medical 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:
- Histologically confirmed, unresectable esophageal or gastric carcinoma (carcinoma=adenocarcinoma or squamous cell carcinoma)
- Measurable disease greater than or equal to 1 cm (longest diameter) by spiral computed tomography (CT) scan or 2 cm or greater by other radiographic technique
- Lesions must be measurable in at least one dimension
- Bone lesions, ascites, and effusions are not measurable
- 18 years of age or older
- ECOG performance status 0 or 1
- Life expectancy of at least 12 weeks
- Adequate bone marrow function
- Adequate renal function
- Adequate liver function
Exclusion Criteria:
- Prior chemotherapy (except as part of pre- or post-operative therapy, completed more than 1 year prior to start day of this protocol)
- History of severe hypersensitivity to bevacizumab, docetaxel, cisplatin, irinotecan, or drugs formulated with polysorbate 80
- Current, recent (within 4 weeks) or planned participation in an experimental drug study
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of need for major surgical procedure during the course of the study
- Minor surgical procedures, such as fine needle aspirations, port-a-cath placement, or core biopsies within 7 days prior to Day 0 of study
- Myocardial infarction or stroke in past 6 months
- Blood pressure of > 150/100 mmHg
- Unstable angina
- New York Heart Association (NYHA) grade II or greater congestive heart failure
- Clinically significant peripheral vascular disease
- Persistent bleeding from primary tumor, while off anticoagulants, requiring repeated transfusions
- Evidence of bleeding diathesis or coagulopathy
- Uncontrolled serious medical or psychiatric illness
- Uncontrolled diarrhea
- Peripheral neuropathy > grade 1
- Clinically apparent central nervous system metastases or carcinomatous meningitis
- Other active malignancy other than non-melanoma skin cancer or in situ cervical carcinoma.
- Urine protein: creatinine ratio of 1.0 or greater at screening
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 1
- Serious non-healing wound, ulcer, or bone fracture
- Pregnant or breast-feeding
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: Docetaxel, Cisplatin, Irinotecan and Bevacizumab (TPCA)
Patients received bevacizumab 10 mg/kg IV on day 1 every 3 weeks while on study.
Additionally, they received docetaxel 30 mg/m2 IV over 30 minutes, followed by cisplatin 25 mg/m2 IV over 30 minutes, followed by irinotecan 50 mg/m2 IV over 30 minutes on days 1 and 8 of each 3-week cycle until disease progression or unacceptable toxicity.
Dose reductions were not permitted for bevacizumab although treatment could be held up to 2 months.
If bevacizumab was discontinued, treatment with other agents could continue.
When docetaxel, cisplatin, or irinotecan was held on day 1 of a cycle, all agents were held.
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다른 이름들:
다른 이름들:
다른 이름들:
다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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10-month Progression-Free Survival Rate
기간: Disease was evaluated radiologically at baseline and every 2 cycles on treatment; Treatment continued until disease progression or unacceptable toxicity. Relevant for this endpoint was disease status at 10 months.
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10-month progression-free survival rate is the probability of patients remaining alive and progression-free at 10-months from study entry estimated using Kaplan-Meier methods.
Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.
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Disease was evaluated radiologically at baseline and every 2 cycles on treatment; Treatment continued until disease progression or unacceptable toxicity. Relevant for this endpoint was disease status at 10 months.
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Best Response
기간: Disease was evaluated radiologically at baseline and every 2 cycles on treatment. Treatment continued until disease progression or unacceptable toxicity. Treatment duration was a median of 6 cycles/18 weeks given 3-week cycle length (range 1-26 cycles).
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Best response on treatment was based on RECIST 1.0 criteria: Complete Response (CR) is complete disappearance of all target lesions; Partial Response (PR) is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD.
Both require confirmation no fewer than 4 weeks apart.
CR/PR assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.
Progressive disease (PD) is at least a 20% increase in the sum of longest diameter of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.
Stable disease is defined as any condition not meeting above criteria.
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Disease was evaluated radiologically at baseline and every 2 cycles on treatment. Treatment continued until disease progression or unacceptable toxicity. Treatment duration was a median of 6 cycles/18 weeks given 3-week cycle length (range 1-26 cycles).
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Overall Survival
기간: Patients in the study cohort were followed for a median of 12.2 month (up to 40 months).
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Overall survival is defined as the time from study entry to death or date last known alive and estimate using Kaplan-Meier (KM) methods.
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Patients in the study cohort were followed for a median of 12.2 month (up to 40 months).
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Progression-Free Survival
기간: Disease was evaluated radiologically at baseline and every 2 cycles on treatment. Treatment continued until disease progression or unacceptable toxicity. Treatment duration was a median of 6 cycles/18 weeks given 3-week cycle length (range 1-26 cycles).
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Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from the study or death.
Patients alive and progression-free at last follow-up are censored.
Per RECIST 1.0 criteria: progressive disease is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.
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Disease was evaluated radiologically at baseline and every 2 cycles on treatment. Treatment continued until disease progression or unacceptable toxicity. Treatment duration was a median of 6 cycles/18 weeks given 3-week cycle length (range 1-26 cycles).
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공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
수사관
- 수석 연구원: Peter Enzinger, MD, Dana-Farber Cancer Institute
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
2006년 9월 1일
기본 완료 (실제)
2008년 11월 1일
연구 완료 (실제)
2016년 10월 1일
연구 등록 날짜
최초 제출
2006년 10월 31일
QC 기준을 충족하는 최초 제출
2006년 10월 31일
처음 게시됨 (추정)
2006년 11월 1일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2017년 8월 1일
QC 기준을 충족하는 마지막 업데이트 제출
2017년 7월 5일
마지막으로 확인됨
2017년 7월 1일
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- 06-100
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
아니요
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