Clinical trial NCT01855061: Biomarker Development for Response Prediction by DNA Mutational Analysis
Official title: Feasibility Study of Biomarker Development for Response Prediction by Large Scale DNA Mutational Analysis of Metastatic Lesions
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Neoplasm Metastasis
Keywords: Feasibility studies
Sequence analysis, DNA
Biological markers
Solid tumors
Neoplasm metastasis
Irinotecan
Pharmacokinetics SN-38
Carboxylesterase activity within metastasis
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
Collaborators: name: Erasmus Medical Center
name: The Netherlands Cancer Institute
First posted: 2013-05-16
Enrollment: 79
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with a metastatic solid tumor who are eligible for (standard of care) treatment with irinotecan.

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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: 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:
measure: Exploration of the correlation between the mutational profile and radiological response according to RECIST-criteria after the first two cycles of chemotherapy.
timeFrame: Analysis 6 weeks after initiation of treatment
measure: Exploration of the correlation between the mutational profile and progression free survival and overall survival.
timeFrame: Overall survival approximately after 2 years of first cycle of irinotecan. Progression free survival approximately 3 months after first irinotecan
measure: Exploration of the correlation between the mutational profile of the index lesion and patient's germline DNA background variation.
timeFrame: Analysis after progressive disease, on average after 3 months.
measure: Differences in mutational profile of metastasis prior to and after exposure to treatment.
timeFrame: Analysis after progressive disease and subsequent post-treatment biopsy, on average after 3 months of treatment
measure: Determine reliable and valid strategies for statistical analysis for biomarker discovery
timeFrame: 2 years
measure: Correlate response to pharmacokinetics of SN-38
timeFrame: After progressive disease and subsequent post-treatment biopsy, in general after 3 months of treatment
measure: 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
timeFrame: After progressive disease and subsequent post-treatment biopsy, in general after 3 months of treatment
measure: Determine clinical applicability of the midazolam phenotyping probe
timeFrame: After first cycle of irinotecan, at three weeks
measure: Number and nature of all (serious) adverse events of study related procedures
timeFrame: 14 days after baseline biopsy and 14 days after post-treatment biopsy (approximately after 3 months of treatment)
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
state: North Holland
city: Rotterdam
country: Netherlands
facility: Erasmsus Medical Center - Daniël den Hoed clinic
state: South Holland
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
Study officials:
affiliation: UMC Utrecht
name: Marlies Langenberg, MD/PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Netherlands Cancer Institute - Antoni van Leeuwenhoek hospital, Amsterdam
name: Neeltje Steeghs, MD/PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Erasmus Medical Center - Daniël den Hoed clinic, Rotterdam
name: Ron Mathijssen, MD/PhD
role: PRINCIPAL_INVESTIGATOR
References: