Imatinib as Pre-operative Anti-Colon Cancer Targeted Therapy

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.

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.

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