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Biomarker Development for Response Prediction by DNA Mutational Analysis (CPCT-01)

2018년 3월 7일 업데이트: 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.

연구 개요

상태

종료됨

정황

개입 / 치료

연구 유형

관찰

등록 (실제)

79

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 장소

  • 네덜란드
      • Utrecht, 네덜란드, 3584 CX
        • University Medical Center Utrecht
    • North Holland
      • Amsterdam, North Holland, 네덜란드, 1066 CX
        • Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
    • South Holland
      • Rotterdam, South Holland, 네덜란드, 3075 EA
        • Erasmsus Medical Center - Daniël den Hoed clinic

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

샘플링 방법

확률 샘플

연구 인구

Patients with a metastatic solid tumor who are eligible for (standard of care) treatment with irinotecan.

설명

Inclusion Criteria:

  1. Patients with a metastatic solid tumor who have failed at least one line of palliative chemotherapy and are irinotecan naïve.
  2. Patients who are, as per local protocol, eligible for palliative treatment with (standard of care) irinotecan.
  3. Measurable metastatic lesion(s), according to RECIST 1.1 criteria.

  4. Radiological measurable metastatic lesion(s) of which a histological biopsy can safely be obtained:

    1. Patients with safely accessible metastases.
    2. Patients not known with bleeding disorders (such as hemophilia) or bleeding complications from biopsies, dental procedures or surgeries.
    3. 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.

    4. 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
    5. Biopsies should be performed at least four weeks after last bevacizumab administration.
  5. 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.

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

코호트 및 개입

그룹/코호트
개입 / 치료
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:

  • pharmacogenetics
  • pharmacokinetics of SN-38
  • carboxylesterase activity in the index lesion
  • midazolam clearance test (only in Rotterdam patients)
절차: Biopsy
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.
다른 이름들:
  • Histological biopsy
절차: Blood samples
Blood samples will be taken at baseline to determine patient's genetic background variation (germline DNA).
다른 이름들:
  • 채혈
절차: Pharmacokinetics
Blood samples will be taken for pharmacokinetic analysis of the active irinotecan metabolite (SN-38).
다른 이름들:
  • PK
  • Pharmacokinetic analysis
  • Pharmacokinetic analyses
절차: Midazolam clearance test
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.
다른 이름들:
  • MCT

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
기간
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.
기간: 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)
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)

2차 결과 측정

결과 측정
기간
Exploration of the correlation between the mutational profile and radiological response according to RECIST-criteria after the first two cycles of chemotherapy.
기간: Analysis 6 weeks after initiation of treatment
Analysis 6 weeks after initiation of treatment
Exploration of the correlation between the mutational profile and progression free survival and overall survival.
기간: Overall survival approximately after 2 years of first cycle of irinotecan. Progression free survival approximately 3 months after first irinotecan
Overall survival approximately after 2 years of first cycle of irinotecan. Progression free survival approximately 3 months after first irinotecan
Exploration of the correlation between the mutational profile of the index lesion and patient's germline DNA background variation.
기간: Analysis after progressive disease, on average after 3 months.
Analysis after progressive disease, on average after 3 months.
Differences in mutational profile of metastasis prior to and after exposure to treatment.
기간: Analysis after progressive disease and subsequent post-treatment biopsy, on average after 3 months of treatment
Analysis after progressive disease and subsequent post-treatment biopsy, on average after 3 months of treatment
Determine reliable and valid strategies for statistical analysis for biomarker discovery
기간: 2 years
2 years
Correlate response to pharmacokinetics of SN-38
기간: After progressive disease and subsequent post-treatment biopsy, in general after 3 months of treatment
After progressive disease and subsequent post-treatment biopsy, in general after 3 months of treatment
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
기간: After progressive disease and subsequent post-treatment biopsy, in general after 3 months of treatment
After progressive disease and subsequent post-treatment biopsy, in general after 3 months of treatment
Determine clinical applicability of the midazolam phenotyping probe
기간: After first cycle of irinotecan, at three weeks
After first cycle of irinotecan, at three weeks
Number and nature of all (serious) adverse events of study related procedures
기간: 14 days after baseline biopsy and 14 days after post-treatment biopsy (approximately after 3 months of treatment)
14 days after baseline biopsy and 14 days after post-treatment biopsy (approximately after 3 months of treatment)

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

P.O. Witteveen

협력자

Erasmus Medical Center
The Netherlands Cancer Institute

수사관

  • 수석 연구원: Marlies Langenberg, MD/PhD, UMC Utrecht
  • 수석 연구원: Neeltje Steeghs, MD/PhD, Netherlands Cancer Institute - Antoni van Leeuwenhoek hospital, Amsterdam
  • 수석 연구원: Ron Mathijssen, MD/PhD, Erasmus Medical Center - Daniël den Hoed clinic, Rotterdam

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

2011년 5월 1일

기본 완료 (실제)

2015년 11월 1일

연구 완료 (실제)

2016년 8월 1일

연구 등록 날짜

최초 제출

2011년 8월 1일

QC 기준을 충족하는 최초 제출

2013년 5월 13일

처음 게시됨 (추정)

2013년 5월 16일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2018년 3월 9일

QC 기준을 충족하는 마지막 업데이트 제출

2018년 3월 7일

마지막으로 확인됨

2018년 3월 1일

추가 정보

이 연구와 관련된 용어

키워드

추가 관련 MeSH 약관

기타 연구 ID 번호

  • NL35198.041.11

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