Docetaxel, Cisplatin, Irinotecan and Bevacizumab (TPCA) in Metastatic Esophageal and Gastric Cancer
2017年7月5日 更新者：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.
調査の概要
詳細な説明
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.
研究の種類
介入
入学 (実際)
38
段階
- フェーズ2
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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Massachusetts
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Boston、Massachusetts、アメリカ、02115
- Dana-Farber Cancer Institute
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Boston、Massachusetts、アメリカ、02114
- Massachusetts General Hospital
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Boston、Massachusetts、アメリカ、02115
- Beth Israel Deaconess Medical Center
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年歳以上 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
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
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的：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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他の名前：
他の名前：
他の名前：
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
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10-month Progression-Free Survival Rate
時間枠：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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Best Response
時間枠：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
時間枠：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
時間枠：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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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
捜査官
- 主任研究者：Peter Enzinger, MD、Dana-Farber Cancer Institute
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始
2006年9月1日
一次修了 (実際)
2008年11月1日
研究の完了 (実際)
2016年10月1日
試験登録日
最初に提出
2006年10月31日
QC基準を満たした最初の提出物
2006年10月31日
最初の投稿 (見積もり)
2006年11月1日
学習記録の更新
投稿された最後の更新 (実際)
2017年8月1日
QC基準を満たした最後の更新が送信されました
2017年7月5日
最終確認日
2017年7月1日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- 06-100
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
いいえ
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