- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01855061
Biomarker Development for Response Prediction by DNA Mutational Analysis (CPCT-01)
Feasibility Study of Biomarker Development for Response Prediction by Large Scale DNA Mutational Analysis of Metastatic Lesions
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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-
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Utrecht, Netherlands, 3584 CX
- University Medical Center Utrecht
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North Holland
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Amsterdam, North Holland, Netherlands, 1066 CX
- Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
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South Holland
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Rotterdam, South Holland, Netherlands, 3075 EA
- Erasmsus Medical Center - Daniël den Hoed clinic
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
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.
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
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.
Other Names:
Blood samples will be taken at baseline to determine patient's genetic background variation (germline DNA).
Other Names:
Blood samples will be taken for pharmacokinetic analysis of the active irinotecan metabolite (SN-38).
Other Names:
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.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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.
Time Frame: 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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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Exploration of the correlation between the mutational profile and radiological response according to RECIST-criteria after the first two cycles of chemotherapy.
Time Frame: 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.
Time Frame: 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.
Time Frame: 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.
Time Frame: 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
Time Frame: 2 years
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2 years
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Correlate response to pharmacokinetics of SN-38
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Marlies Langenberg, MD/PhD, UMC Utrecht
- Principal Investigator: Neeltje Steeghs, MD/PhD, Netherlands Cancer Institute - Antoni van Leeuwenhoek hospital, Amsterdam
- Principal Investigator: Ron Mathijssen, MD/PhD, Erasmus Medical Center - Daniël den Hoed clinic, Rotterdam
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms
- Neoplastic Processes
- Neoplasm Metastasis
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Anesthetics, Intravenous
- Anesthetics, General
- Anesthetics
- Tranquilizing Agents
- Psychotropic Drugs
- Hypnotics and Sedatives
- Adjuvants, Anesthesia
- Anti-Anxiety Agents
- GABA Modulators
- GABA Agents
- Midazolam
Other Study ID Numbers
- NL35198.041.11
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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