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

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
5

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • Netherlands
      • Utrecht, Netherlands, 3584CX
        • University Medical Center Utrecht
      • Utrecht, Netherlands, 3582KE
        • Diakonessenhuis
    • Utrecht
      • Amersfoort, Utrecht, Netherlands, 3813TZ
        • Meander Medical Center

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Male or female aged ≥18 years
  2. Histologically proven adenocarcinoma of the colon;
  3. Completed cancer staging with CT-abdomen and CT-thorax/X-thorax according to hospital's standard of care;
  4. Confirmed eligibility for surgery with curative intent as deemed by the hospital's multidisciplinary board (MDB) review;
  5. 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);
  6. Minimum of four properly stored pre-treatment biopsies for gene expression analysis/ELISA;
  7. WHO performance status 0 or 1;

  8. 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
  9. Willingness and ability to comply with scheduled visits, treatment plans and laboratory tests;
  10. Written informed consent.

Exclusion Criteria:

  1. The presence of synchronous distant metastases;
  2. Current hospital standard of care dictates that subject should undergo any neoadjuvant therapy;
  3. 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;
  4. 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;
  5. Known HIV or Hepatitis B/C infection;
  6. Known symptomatic congestive heart failure;
  7. 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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.
Drug: Imatinib
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:
  • Gleevec
  • STI571

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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)
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.
period from diagnostic colonoscopy until surgical resection (~5 weeks)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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)
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.
period from diagnostic colonoscopy until surgical resection (~5 weeks)
Correlation between plasma imatinib trough levels on day 14 and intratumoural concentration of imatinib in the resection specimen
Time Frame: at time of surgery
at time of surgery
Correlation between the extent of PDGFR and cKIT inhibition and systemic and intratumoural imatinib and CGP74588 concentration
Time Frame: at time of surgery
at time of surgery
Change in plasma CEA-concentrations
Time Frame: period between diagnostic colonoscopy until surgical resection (~5 weeks)
period between diagnostic colonoscopy until surgical resection (~5 weeks)
Change in plasma levels of circulating tumor DNA
Time Frame: period between diagnostic colonoscopy until surgical resection (~5 weeks)
period between diagnostic colonoscopy until surgical resection (~5 weeks)
Effects of imatinib on the ability of cancer cells to form in vitro 3D cell cultures (organoids)
Time Frame: at time of surgery
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.
at time of surgery
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
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).
from start of treatment until 2 weeks after last dose imatinib

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
UMC Utrecht

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Erasmus Medical Center
Meander Medical Center
Hubrecht Institute

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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.

General Publications

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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 9, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 12, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 18, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 14, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 9, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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