Biomarker Development for Response Prediction by DNA Mutational Analysis (CPCT-01)
2018年3月7日 更新者：P.O. Witteveen
Feasibility Study of Biomarker Development for Response Prediction by Large Scale DNA Mutational Analysis of Metastatic Lesions
The purpose of this study is to determine whether it is possible to predict response to chemotherapy in patients with metastatic cancer who are treated with irinotecan by determining the mutational profile of the tumor.
調査の概要
研究の種類
観察的
入学 (実際)
79
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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Utrecht、オランダ、3584 CX
- University Medical Center Utrecht
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North Holland
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Amsterdam、North Holland、オランダ、1066 CX
- Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
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South Holland
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Rotterdam、South Holland、オランダ、3075 EA
- Erasmsus Medical Center - Daniël den Hoed clinic
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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
サンプリング方法
確率サンプル
調査対象母集団
Patients with a metastatic solid tumor who are eligible for (standard of care) treatment with irinotecan.
説明
Inclusion Criteria:
- Patients with a metastatic solid tumor who have failed at least one line of palliative chemotherapy and are irinotecan naïve.
- Patients who are, as per local protocol, eligible for palliative treatment with (standard of care) irinotecan.
- Measurable metastatic lesion(s), according to RECIST 1.1 criteria.
Radiological measurable metastatic lesion(s) of which a histological biopsy can safely be obtained:
- Patients with safely accessible metastases.
- Patients not known with bleeding disorders (such as hemophilia) or bleeding complications from biopsies, dental procedures or surgeries.
- Patients not using any anti-coagulant medication at the time of biopsy: all aspirin derivatives, NSAID's, coumarines, platelet function inhibitors, heparins (including LMWHs) and oral factor Xa inhibitors are not allowed, unless medication can either be safely stopped or counteracted.
Adequate coagulation status on the day of biopsy as measured by:
- PTT < 1.5 x ULN
- APTT < 1.5 x ULN
- Platelet count 100 x 10*9 / L or higher
- PT-INR < 1.6
- HB > 6
- Biopsies should be performed at least four weeks after last bevacizumab administration.
- Patients age 18 years or up, willing and able to comply with the protocol as judged by the investigator with a signed informed consent.
Exclusion Criteria:
Patients not meeting all of the above inclusion criteria.
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
コホートと介入
グループ/コホート |
介入・治療 |
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Irinotecan
Patients will be subjected to a their metastatic solid tumor. Radiological response will be evaluated after each 2 cycles: 1. percentage change in radiological volume of the "index lesion" (radiological measurable lesion that underwent biopsy) after the first two cycles of irinotecan; 2. radiological response according to RECIST 1.1 after each 2 cycles. Patients are intended to receive irinotecan until progressive disease or unacceptable toxicity. Patients will be subjected to another biopsy of the index lesion at definitive discontinuation of irinotecan. Patients will also be subjected to blood draws for determining patient's genetic background variation. Side studies include:
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Histological biopsy of the "index lesion" (a radiological measurable lesion on which biopsy is performed) at baseline, as well as when showing progressive disease.
Histological biopsies will be subjected to DNA sequencing to assess the mutational profile, as well as to analysis of carboxylesterase activity.
他の名前：
Blood samples will be taken at baseline to determine patient's genetic background variation (germline DNA).
他の名前：
Blood samples will be taken for pharmacokinetic analysis of the active irinotecan metabolite (SN-38).
他の名前：
Patients who are being treated in Rotterdam will be subjected to blood draws for validation of the earlier developed midazolam phenotyping test (midazolam clearance test), which may be an indicator for pharmacokinetics of irinotecan.
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 |
時間枠 |
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Exploration of the correlation between the mutational profile and the percentage change in volumetric measurement of the index lesion after the first two cycles of chemotherapy.
時間枠：Change in radiological volume of the index lesion after the first 2 cycles of irinotecan. Radiological response (according to RECIST 1.1) after the first 2 cycles of irinotecan (i.e. after 2 x 3 weeks = 6 weeks)
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Change in radiological volume of the index lesion after the first 2 cycles of irinotecan. Radiological response (according to RECIST 1.1) after the first 2 cycles of irinotecan (i.e. after 2 x 3 weeks = 6 weeks)
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二次結果の測定
結果測定 |
時間枠 |
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Exploration of the correlation between the mutational profile and radiological response according to RECIST-criteria after the first two cycles of chemotherapy.
時間枠：Analysis 6 weeks after initiation of treatment
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Analysis 6 weeks after initiation of treatment
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Exploration of the correlation between the mutational profile and progression free survival and overall survival.
時間枠：Overall survival approximately after 2 years of first cycle of irinotecan. Progression free survival approximately 3 months after first irinotecan
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Overall survival approximately after 2 years of first cycle of irinotecan. Progression free survival approximately 3 months after first irinotecan
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Exploration of the correlation between the mutational profile of the index lesion and patient's germline DNA background variation.
時間枠：Analysis after progressive disease, on average after 3 months.
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Analysis after progressive disease, on average after 3 months.
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Differences in mutational profile of metastasis prior to and after exposure to treatment.
時間枠：Analysis after progressive disease and subsequent post-treatment biopsy, on average after 3 months of treatment
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Analysis after progressive disease and subsequent post-treatment biopsy, on average after 3 months of treatment
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Determine reliable and valid strategies for statistical analysis for biomarker discovery
時間枠：2 years
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2 years
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Correlate response to pharmacokinetics of SN-38
時間枠：After progressive disease and subsequent post-treatment biopsy, in general after 3 months of treatment
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After progressive disease and subsequent post-treatment biopsy, in general after 3 months of treatment
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Determine carboxylesterase activity in metastatic tumor material (pre- and posttreatment) and correlate intra-tumoral carboxylesterase activity to systemic SN-38 pharmacokinetics and to irinotecan response
時間枠：After progressive disease and subsequent post-treatment biopsy, in general after 3 months of treatment
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After progressive disease and subsequent post-treatment biopsy, in general after 3 months of treatment
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Determine clinical applicability of the midazolam phenotyping probe
時間枠：After first cycle of irinotecan, at three weeks
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After first cycle of irinotecan, at three weeks
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Number and nature of all (serious) adverse events of study related procedures
時間枠：14 days after baseline biopsy and 14 days after post-treatment biopsy (approximately after 3 months of treatment)
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14 days after baseline biopsy and 14 days after post-treatment biopsy (approximately after 3 months of treatment)
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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。
スポンサー
捜査官
- 主任研究者：Marlies Langenberg, MD/PhD、UMC Utrecht
- 主任研究者：Neeltje Steeghs, MD/PhD、Netherlands Cancer Institute - Antoni van Leeuwenhoek hospital, Amsterdam
- 主任研究者：Ron Mathijssen, MD/PhD、Erasmus Medical Center - Daniël den Hoed clinic, Rotterdam
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
2011年5月1日
一次修了 (実際)
2015年11月1日
研究の完了 (実際)
2016年8月1日
試験登録日
最初に提出
2011年8月1日
QC基準を満たした最初の提出物
2013年5月13日
最初の投稿 (見積もり)
2013年5月16日
学習記録の更新
投稿された最後の更新 (実際)
2018年3月9日
QC基準を満たした最後の更新が送信されました
2018年3月7日
最終確認日
2018年3月1日
詳しくは
本研究に関する用語
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