- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02685046
Imatinib as Pre-operative Anti-Colon Cancer Targeted Therapy (ImPACCT)
October 9, 2019 updated by: Prof dr I.H.M. Borel Rinkes, UMC Utrecht
Targeted Therapy With Imatinib for Treatment of Poor Prognosis Mesenchymal-type Resectable Colon Cancer: a Proof-of-concept Study in the Preoperative Window Period.
In this proof-of-concept trial the investigators will study the effects of imatinib treatment on the biology of mesenchymal-type colon cancers.
Study Overview
Detailed Description
Tumor biopsies from patients with newly diagnosed colon cancer will be pre-screened with an RT-qPCR test to identify tumors of the mesenchymal subtype.
Patients with mesenchymal-type tumors that meet the in- and exclusion criteria will be treated with imatinib during the "window period" that normally precedes surgery.
Immediately following tumor resection, biopsies will be taken from the surgical specimen.
Gene and protein expression of the pre- and post-treatments biopsies will be compared to assess the effects of imatinib therapy on PDGFR- and cKIT-signalling and on the mesenchymal gene expression profile.
Study Type
Interventional
Enrollment (Actual)
5
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Utrecht, Netherlands, 3584CX
- University Medical Center Utrecht
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Utrecht, Netherlands, 3582KE
- Diakonessenhuis
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Utrecht
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Amersfoort, Utrecht, Netherlands, 3813TZ
- Meander Medical Center
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Male or female aged ≥18 years
- Histologically proven adenocarcinoma of the colon;
- Completed cancer staging with CT-abdomen and CT-thorax/X-thorax according to hospital's standard of care;
- Confirmed eligibility for surgery with curative intent as deemed by the hospital's multidisciplinary board (MDB) review;
- An intratumoural gene expression profile of PDGFR-α, PDGFR-β, PDGF-C and KIT, indicative of the mesenchymal phenotype, according to our diagnostic RT-qPCR test (i.e. more than 50% chance of having the mesenchymal phenotype);
- Minimum of four properly stored pre-treatment biopsies for gene expression analysis/ELISA;
- WHO performance status 0 or 1;
Adequate haematology status and organ function, defined as:
- Normal creatinine clearance (≥60 ml/min (MRDR))
- ALAT within 2.5x upper limit of normal (ULN)
- PT-INR < 1.5
- Leukocytes > 1,5*10^9/L; Hb > 6.0 mmol/L; platelets > 100*10^9/L
- Willingness and ability to comply with scheduled visits, treatment plans and laboratory tests;
- Written informed consent.
Exclusion Criteria:
- The presence of synchronous distant metastases;
- Current hospital standard of care dictates that subject should undergo any neoadjuvant therapy;
- Concurrent participation in another clinical trial using any medicinal product, or participation in such a trial in the period of three months prior to the current trial;
- Women who are pregnant, plan to become pregnant or are lactating during the study or for up to 30 days after the last dose of imatinib;
- Known HIV or Hepatitis B/C infection;
- Known symptomatic congestive heart failure;
- Co-morbidity requiring concomitant treatment with drugs that act as strong inducers of CYP3A4 or with drugs with a narrow therapeutic range influenced by imatinib
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Intervention
Subjects will be treated with the medicinal product imatinib, which will be administered orally in tablets of 400mg, once per day, during two weeks prior to tumor resection.
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Subjects will be treated with the medicinal product imatinib, which will be administered orally in tablets of 400mg, once per day, during two weeks prior to tumor resection.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Effects of treatment on the mesenchymal gene expression profile
Time Frame: period from diagnostic colonoscopy until surgical resection (~5 weeks)
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To assess the extent of change in the mesenchymal phenotype, gene expression arrays will be generated from pre- and post-treatment tissue samples and the expression of genes associated with the poor-prognosis mesenchymal subtype will be compared.
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period from diagnostic colonoscopy until surgical resection (~5 weeks)
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Extent of targeted inhibition of PDGFR and KIT phosphorylation in cancer cells
Time Frame: period from diagnostic colonoscopy until surgical resection (~5 weeks)
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I. Measurement of PDGFR and cKIT inhibition by comparison of the fraction of autophosphorylated PDGFR and cKIT pre-treatment versus post-treatment, measured with ELISA on tissue samples derived from diagnostic biopsies and surgery.
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period from diagnostic colonoscopy until surgical resection (~5 weeks)
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Correlation between plasma imatinib trough levels on day 14 and intratumoural concentration of imatinib in the resection specimen
Time Frame: at time of surgery
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at time of surgery
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Correlation between the extent of PDGFR and cKIT inhibition and systemic and intratumoural imatinib and CGP74588 concentration
Time Frame: at time of surgery
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at time of surgery
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Change in plasma CEA-concentrations
Time Frame: period between diagnostic colonoscopy until surgical resection (~5 weeks)
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period between diagnostic colonoscopy until surgical resection (~5 weeks)
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Change in plasma levels of circulating tumor DNA
Time Frame: period between diagnostic colonoscopy until surgical resection (~5 weeks)
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period between diagnostic colonoscopy until surgical resection (~5 weeks)
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Effects of imatinib on the ability of cancer cells to form in vitro 3D cell cultures (organoids)
Time Frame: at time of surgery
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V. The ability to establish organoids from imatinib-treated tumours will be compared with the general success rate of organoid formation from colon tumours at the Hubrecht Institute.
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at time of surgery
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Number of participants with treatment-related adverse events as assessed by CTCAEv4.02
Time Frame: from start of treatment until 2 weeks after last dose imatinib
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The occurrence, frequency and severity of adverse events during preoperative treatment with imatinib, peroperatively or in the postoperative period (up to 14 days after tumour resection).
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from start of treatment until 2 weeks after last dose imatinib
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: I HM Borel Rinkes, MD, PhD, UMC Utrecht
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
April 1, 2016
Primary Completion (Actual)
September 1, 2019
Study Completion (Actual)
September 1, 2019
Study Registration Dates
First Submitted
February 9, 2016
First Submitted That Met QC Criteria
February 12, 2016
First Posted (Estimate)
February 18, 2016
Study Record Updates
Last Update Posted (Actual)
October 14, 2019
Last Update Submitted That Met QC Criteria
October 9, 2019
Last Verified
October 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Colorectal Neoplasms
- Colonic Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Imatinib Mesylate
Other Study ID Numbers
- CC-TT-IMA-14
- NL50620.041.15 (Registry Identifier: CCMO)
- 2014-003965-11 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
UNDECIDED
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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