Neoplasm MetastasisCPCT-01NCT01855061
Biomarker Development for Response Prediction by DNA Mutational Analysis
An observational study of Neoplasm Metastasis, run by P.O. Witteveen at 3 sites in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasm Metastasis
- What is being tested?
- Biopsy, Blood samples and Pharmacokinetics
- Type of treatment
- Surgery or procedure
- How many people
- 79 participants
- Where
- 3 sitesNetherlands
- Study dates
- May 2011to Aug 2016
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with a metastatic solid tumor who are eligible for (standard of care) treatment with irinotecan.
Who may be able to join
- 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.
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- 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.
Who cannot join
- Patients not meeting all of the above inclusion criteria.
Trial locations and contacts
3 sites in 1 country.
Netherlands3 sites
Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital
Amsterdam, North Holland, 1066 CX
Erasmsus Medical Center - Daniël den Hoed clinic
Rotterdam, South Holland, 3075 EA
University Medical Center Utrecht
Utrecht, 3584 CX
About this study
Official title: 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.
- Conditions
- Neoplasm Metastasis
- Being tested
- Biopsy, Blood samples, Pharmacokinetics, Midazolam clearance test
- Keywords
- Feasibility studies, Sequence analysis, DNA, Biological markers, Solid tumors, Neoplasm metastasis, Irinotecan, Pharmacokinetics SN-38, Carboxylesterase activity within metastasis
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BiopsyProcedure or surgery
Also called Histological 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.
Blood samplesProcedure or surgery
Also called Blood sampling
Blood samples will be taken at baseline to determine patient's genetic background variation (germline DNA).
PharmacokineticsProcedure or surgery
Also called PK, Pharmacokinetic analysis, Pharmacokinetic analyses
Blood samples will be taken for pharmacokinetic analysis of the active irinotecan metabolite (SN-38).
Midazolam clearance testProcedure or surgery
Also called MCT
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.
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: Procedure: Biopsy; Procedure: Blood samples; Procedure: Pharmacokinetics; Procedure: Midazolam clearance test |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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 (9)
Exploration of the correlation between the mutational profile and radiological response according to RECIST-criteria after the first two cycles of chemotherapy.
Measured: Analysis 6 weeks after initiation of treatment
Exploration of the correlation between the mutational profile and progression free survival and overall survival.
Measured: 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.
Measured: Analysis after progressive disease, on average after 3 months.
Differences in mutational profile of metastasis prior to and after exposure to treatment.
Measured: 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
Measured: 2 years
Correlate response to pharmacokinetics of SN-38
Measured: 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
Measured: After progressive disease and subsequent post-treatment biopsy, in general after 3 months of treatment
Determine clinical applicability of the midazolam phenotyping probe
Measured: After first cycle of irinotecan, at three weeks
Number and nature of all (serious) adverse events of study related procedures
Measured: 14 days after baseline biopsy and 14 days after post-treatment biopsy (approximately after 3 months of treatment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2013 (estimated)
- Study startMay 2011
- Primary completionNov 2015
- Study completionAug 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neoplasm MetastasisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 79 participants (actual)
Sponsor and investigators
- Lead sponsor
- P.O. Witteveen
- Sponsor type
- University, hospital or other
- Collaborators
- Erasmus Medical Center, The Netherlands Cancer Institute
- Responsible party
- Sponsor-investigator, P.O. Witteveen, UMC Utrecht
- Investigators
- Marlies Langenberg, MD/PhD, Principal investigator, UMC UtrechtNeeltje Steeghs, MD/PhD, Principal investigator, Netherlands Cancer Institute - Antoni van Leeuwenhoek hospital, AmsterdamRon Mathijssen, MD/PhD, Principal investigator, Erasmus Medical Center - Daniël den Hoed clinic, Rotterdam
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01855061
- Sponsor's protocol ID
- NL35198.041.11
- Acronym
- CPCT-01
- Status last verified
- Mar 2018
- First submitted
- 1 Aug 2011
- Last updated
- 9 Mar 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Feasibility Study of Biomarker Development for Response Prediction by Large Scale DNA Mutational Analysis of Metastatic Lesions
- ClinicalTrials.gov ID
- NCT01855061
- Acronym / sponsor ID
- CPCT-01 / NL35198.041.11
- Conditions
- Neoplasm Metastasis
- Keywords
- Feasibility studies, Sequence analysis, DNA, Biological markers, Solid tumors, Neoplasm metastasis, Irinotecan, Pharmacokinetics SN-38, Carboxylesterase activity within metastasis
- Study type
- Observational
- Recruitment status
- Terminated
- Enrolment
- 79 participants (actual)
- Lead sponsor
- P.O. WitteveenUniversity, hospital or other
- Collaborators
- Erasmus Medical Center, The Netherlands Cancer Institute
- Study start
- May 2011
- Primary completion
- Nov 2015 (actual)
- Study completion
- Aug 2016 (actual)
- First posted
- 16 May 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Irinotecan | – | Procedure: Biopsy, Procedure: Blood samples, Procedure: Pharmacokinetics, Procedure: Midazolam clearance testPatients 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) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with a metastatic solid tumor who are eligible for (standard of care) treatment with irinotecan.
Key inclusion criteria (15 listed)
- 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 age 18 years or up, willing and able to comply with the protocol as judged by the investigator with a signed informed consent.
Key exclusion criteria (1 listed)
- Patients not meeting all of the above inclusion criteria.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BiopsyAlso: Histological biopsyHistological 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. | Procedure or surgery | Irinotecan |
| Blood samplesAlso: Blood samplingBlood samples will be taken at baseline to determine patient's genetic background variation (germline DNA). | Procedure or surgery | Irinotecan |
| PharmacokineticsAlso: PK, Pharmacokinetic analysis, Pharmacokinetic analysesBlood samples will be taken for pharmacokinetic analysis of the active irinotecan metabolite (SN-38). | Procedure or surgery | Irinotecan |
| Midazolam clearance testAlso: MCTPatients 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. | Procedure or surgery | Irinotecan |
Primary outcome
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)
9 secondary outcomes
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
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
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.
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
Determine reliable and valid strategies for statistical analysis for biomarker discovery
Time frame: 2 years
Correlate response to pharmacokinetics of SN-38
Time frame: 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
Time frame: After progressive disease and subsequent post-treatment biopsy, in general after 3 months of treatment
Determine clinical applicability of the midazolam phenotyping probe
Time frame: After first cycle of irinotecan, at three weeks
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)
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marlies Langenberg, MD/PhD principal investigator
UMC Utrecht
Neeltje Steeghs, MD/PhD principal investigator
Netherlands Cancer Institute - Antoni van Leeuwenhoek hospital, Amsterdam
Ron Mathijssen, MD/PhD principal investigator
Erasmus Medical Center - Daniël den Hoed clinic, Rotterdam
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Neoplasm Metastasis, run by P.O. Witteveen at 3 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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. (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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2018.