Imatinib as Pre-operative Anti-Colon Cancer Targeted Therapy

NCT ID: NCT02685046

Last Updated: 2019-10-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-04-30
• Study Completion Date: 2019-09-01

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.

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.

Conditions

Colonic Neoplasms

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Imatinib

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Gleevec; STI571

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Meander Medical Center

OTHER

Sponsor Role: collaborator

Erasmus Medical Center

OTHER

Sponsor Role: collaborator

Hubrecht Institute

UNKNOWN

Sponsor Role: collaborator

UMC Utrecht

OTHER

Sponsor Role: lead

Responsible Party

Prof dr I.H.M. Borel Rinkes

Chief Surgical Specialities

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

I HM Borel Rinkes, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

UMC Utrecht

Locations

Meander Medical Center

Amersfoort, Utrecht, Netherlands

Diakonessenhuis

Utrecht, , Netherlands

University Medical Center Utrecht

Utrecht, , Netherlands

Countries

Netherlands

References

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.

Reference Type: DERIVED

PMID: 28424071 (View on PubMed)

Other Identifiers

NL50620.041.15

Identifier Type: REGISTRY

Identifier Source: secondary_id

2014-003965-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CC-TT-IMA-14

Identifier Type: -

Identifier Source: org_study_id