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Imatinib as Pre-operative Anti-Colon Cancer Targeted Therapy (ImPACCT)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2016 by UMC Utrecht
Sponsor:
Collaborators:
Meander Medical Center
Erasmus Medical Center
Hubrecht Institute
Information provided by (Responsible Party):
Prof dr I.H.M. Borel Rinkes, UMC Utrecht
ClinicalTrials.gov Identifier:
NCT02685046
First received: February 9, 2016
Last updated: October 24, 2016
Last verified: October 2016
  Purpose
In this proof-of-concept trial the investigators will study the effects of imatinib treatment on the biology of mesenchymal-type colon cancers.

Condition Intervention Phase
Colonic Neoplasms
Drug: Imatinib
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Targeted Therapy With Imatinib for Treatment of Poor Prognosis Mesenchymal-type Resectable Colon Cancer: a Proof-of-concept Study in the Preoperative Window Period.

Resource links provided by NLM:


Further study details as provided by UMC Utrecht:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.

  • Correlation between plasma imatinib trough levels on day 14 and intratumoural concentration of imatinib in the resection specimen [ Time Frame: 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 ]
  • Change in plasma CEA-concentrations [ Time Frame: 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) ]
  • 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.

  • 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).


Estimated Enrollment: 27
Study Start Date: April 2016
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02685046

Contacts
Contact: Inge Ubink, MD, MSc i.ubink-3@umcutrecht.nl
Contact: Haiko J Bloemendal, MD, PhD hj.bloemendal@meandermc.nl

Locations
Netherlands
Meander Medical Center Recruiting
Amersfoort, Utrecht, Netherlands, 3813TZ
Contact: Haiko J Bloemendal       hj.bloemendal@meandermc.nl   
Principal Investigator: H J Bloemendal, MD         
Sub-Investigator: M A Brink, MD         
Sub-Investigator: M P Schwartz, MD         
Sponsors and Collaborators
UMC Utrecht
Meander Medical Center
Erasmus Medical Center
Hubrecht Institute
Investigators
Principal Investigator: I HM Borel Rinkes, MD, PhD UMC Utrecht
  More Information

Responsible Party: Prof dr I.H.M. Borel Rinkes, Chief Surgical Specialities, UMC Utrecht
ClinicalTrials.gov Identifier: NCT02685046     History of Changes
Other Study ID Numbers: CC-TT-IMA-14
NL50620.041.15 ( Registry Identifier: CCMO )
2014-003965-11 ( EudraCT Number )
Study First Received: February 9, 2016
Last Updated: October 24, 2016
Individual Participant Data  
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
Colonic Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Imatinib Mesylate
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 28, 2017