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

7 marzo 2018 aggiornato da: 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.

Panoramica dello studio

Stato

Terminato

Condizioni

Intervento / Trattamento

Tipo di studio

Osservativo

Iscrizione (Effettivo)

79

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

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

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

18 anni e precedenti (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Metodo di campionamento

Campione di probabilità

Popolazione di studio

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

Descrizione

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.

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

Coorti e interventi

Gruppo / Coorte
Intervento / Trattamento
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)
Procedura: 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.
Altri nomi:
  • Histological biopsy
Procedura: Blood samples
Blood samples will be taken at baseline to determine patient's genetic background variation (germline DNA).
Altri nomi:
  • Prelievo di sangue
Procedura: Pharmacokinetics
Blood samples will be taken for pharmacokinetic analysis of the active irinotecan metabolite (SN-38).
Altri nomi:
  • PK
  • Pharmacokinetic analysis
  • Pharmacokinetic analyses
Procedura: 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.
Altri nomi:
  • MCT

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Lasso di tempo
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.
Lasso di tempo: 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)

Misure di risultato secondarie

Misura del risultato
Lasso di tempo
Exploration of the correlation between the mutational profile and radiological response according to RECIST-criteria after the first two cycles of chemotherapy.
Lasso di tempo: 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.
Lasso di tempo: 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.
Lasso di tempo: 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.
Lasso di tempo: 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
Lasso di tempo: 2 years
2 years
Correlate response to pharmacokinetics of SN-38
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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)

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

P.O. Witteveen

Collaboratori

Erasmus Medical Center
The Netherlands Cancer Institute

Investigatori

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

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio

1 maggio 2011

Completamento primario (Effettivo)

1 novembre 2015

Completamento dello studio (Effettivo)

1 agosto 2016

Date di iscrizione allo studio

Primo inviato

1 agosto 2011

Primo inviato che soddisfa i criteri di controllo qualità

13 maggio 2013

Primo Inserito (Stima)

16 maggio 2013

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

9 marzo 2018

Ultimo aggiornamento inviato che soddisfa i criteri QC

7 marzo 2018

Ultimo verificato

1 marzo 2018

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • NL35198.041.11

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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