Imatinib as Pre-operative Anti-Colon Cancer Targeted Therapy

NCT02685046 | Terminated Phase 2 DMC

• 3 other identifiers: CC-TT-IMA-14NL50620.041.152014-003965-11
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 3

Brief Summary

In this proof-of-concept trial the investigators will study the effects of imatinib treatment on the biology of mesenchymal-type colon cancers.

Conditions

Colonic Neoplasms

Outcome Measures

Primary Outcomes (1)

• Effects of treatment on the mesenchymal gene expression profile

  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 Outcomes (7)

• Extent of targeted inhibition of PDGFR and KIT phosphorylation in cancer cells

  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

  at time of surgery

• Correlation between the extent of PDGFR and cKIT inhibition and systemic and intratumoural imatinib and CGP74588 concentration

  at time of surgery

• Change in plasma CEA-concentrations

  period between diagnostic colonoscopy until surgical resection (~5 weeks)

• Change in plasma levels of circulating tumor DNA

  period between diagnostic colonoscopy until surgical resection (~5 weeks)

Study Arms (1)

Intervention

EXPERIMENTAL

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

Interventions

Imatinib DRUG

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.

Also known as: Gleevec, STI571

Intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• UMC Utrecht: lead
• Meander Medical Center: collaborator
• Erasmus Medical Center: collaborator
• Hubrecht Institute: collaborator

Study Sites (3)

Meander Medical Center

Amersfoort, Utrecht, 3813TZ, Netherlands

Location

Diakonessenhuis

Utrecht, 3582KE, Netherlands

Location

University Medical Center Utrecht

Utrecht, 3584CX, Netherlands

Location

Related Publications (1)

• Ubink I, Bloemendal HJ, Elias SG, Brink MA, Schwartz MP, Holierhoek YCW, Verheijen PM, Boerman AW, Mathijssen RHJ, de Leng WWJ, de Weger RA, van Grevenstein WMU, Koopman M, Lolkema MP, Kranenburg O, Borel Rinkes IHM. Imatinib treatment of poor prognosis mesenchymal-type primary colon cancer: a proof-of-concept study in the preoperative window period (ImPACCT). BMC Cancer. 2017 Apr 19;17(1):282. doi: 10.1186/s12885-017-3264-y.

  PMID: 28424071 DERIVED

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

Imatinib Mesylate

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• I HM Borel Rinkes, MD, PhD

  UMC Utrecht

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Surgical Specialities

Study Record Dates

• First Submitted: February 9, 2016
• First Posted: February 18, 2016
• Study Start: April 1, 2016
• Primary Completion: September 1, 2019
• Study Completion: September 1, 2019
• Last Updated: October 14, 2019

Record last verified: 2019-10

Locations

NL (3)