Feasibility Study of Biomarker Development for Response Prediction by Large Scale DNA Mutational Analysis of Metastatic Lesions

P.O. Witteveen3 sites in 1 country79 target enrollmentMay 2011

ConditionsNeoplasm Metastasis

Overview

Phase: Not Applicable
Intervention: Not specified
Conditions: Neoplasm Metastasis
Sponsor: P.O. Witteveen
Enrollment: 79
Locations: 3
Primary Endpoint: 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.
Status: Terminated
Last Updated: 8 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

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.

Registry

clinicaltrials.gov

Start Date

May 2011

End Date

August 2016

Last Updated

8 years ago

Study Type

Observational

Sex

All

Investigators

Sponsor

P.O. Witteveen

Responsible Party

Sponsor Investigator

Principal Investigator

P.O. Witteveen

Investigator

UMC Utrecht

Eligibility Criteria

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

Exclusion Criteria

•Patients not meeting all of the above inclusion criteria.

Outcomes

Primary Outcomes

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)

Secondary Outcomes

Exploration of the correlation between the mutational profile and radiological response according to RECIST-criteria after the first two cycles of chemotherapy.(Analysis 6 weeks after initiation of treatment)
Exploration of the correlation between the mutational profile and progression free survival and overall survival.(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.(Analysis after progressive disease, on average after 3 months.)
Correlate response to pharmacokinetics of SN-38(After progressive disease and subsequent post-treatment biopsy, in general after 3 months of treatment)
Differences in mutational profile of metastasis prior to and after exposure to 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(2 years)
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(After progressive disease and subsequent post-treatment biopsy, in general after 3 months of treatment)
Determine clinical applicability of the midazolam phenotyping probe(After first cycle of irinotecan, at three weeks)
Number and nature of all (serious) adverse events of study related procedures(14 days after baseline biopsy and 14 days after post-treatment biopsy (approximately after 3 months of treatment))