Temsirolimus and Irinotecan for Treatment Resistant Patients With Metastatic Colorectal Cancer and KRAS Mutations (TIRASMUS)

This study has been completed.
Sponsor:
Information provided by:
Vejle Hospital
ClinicalTrials.gov Identifier:
NCT00827684
First received: January 22, 2009
Last updated: June 7, 2011
Last verified: June 2011
  Purpose

The purpose of this study is to investigate the safety and efficacy of temsirolimus as a single drug, and of temsirolimus in combination with irinotecan in chemotherapy resistant patients with KRAS mutated colorectal cancer.


Condition Intervention Phase
Metastatic Colorectal Cancer
Drug: Irinotecan
Drug: Temsirolimus
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Primary Purpose: Treatment
Official Title: Phase II Study of Temsirolimus and Irinotecan in Chemotherapy Refractory Patients With KRAS Mutated Metastatic Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by Vejle Hospital:

Primary Outcome Measures:
  • Objective response rates

Secondary Outcome Measures:
  • Progression free survival
  • Overall survival
  • Translational Research

Estimated Enrollment: 50
Study Start Date: March 2009
Study Completion Date: June 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Response or stable disease
will receive Temsirolimus
Drug: Temsirolimus
Experimental: Progression
Will receive a combination of Temsirolimus and Irinotecan
Drug: Irinotecan Drug: Temsirolimus

Detailed Description:

Chemotherapy resistance is a major challenge in metastatic colorectal cancer (mCRC), and EGFR inhibitors have been introduced as 3rd line treatment to chemotherapy refractory patients. However, it has recently been established that response to treatment with irinotecan and cetuximab is confined to patients with wtKRAS tumors. Therefore, downstream targets are being proposed as potential inhibitors of the EGFR signalling in tumours with KRAS mutations. mTOR is a central intracellular signalling molecule and a rational approach for potential reversion of chemotherapy resistance in these patients.

Preclinical data suggest that different solid tumors could respond to mTOR inhibitors and report on enhanced antitumor activity in combination with different traditional cytostatic drugs. Furthermore recent preclinical data suggest that mTOR inhibition may induce tumor reduction in colon cancer xenographs. Temsirolimus (CCI-779) has been widely investigated in different clinical settings and is presently registered for treatment of renal cell carcinomas. Furthermore, is has recently shown response in metastatic breast cancer patients, but at present there are no clinical data on efficacy or safety in metastatic colorectal cancer patients.

The present study aims at investigating the safety and efficacy of monotherapy temsirolimus and a combination of temsirolimus and irinotecan in chemotherapy resistant, KRAS mutated colorectal adenocarcinomas.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically verified colorectal adenocarcinomas
  • Age > 18 years and < 70
  • Metastatic colorectal cancer refractory 5-FU, oxaliplatin and irinotecan containing treatment regimes
  • KRAS mutation detected by DxS kit in primary tumor or metastatic lesion.
  • Measurable disease according to RECIST
  • ECOG performance status 0, 1 or 2
  • Adequate renal, hepatic and haematological function
  • Normal serum cholesterol and triglycerides
  • Blood samples and available paraffin embedded tumor material for translational research studies
  • Fertile males and females (< 2 years after last period for women) must use effective birth control
  • Signed Informed consent

Exclusion Criteria:

  • Clinically significant heart disease, active severe infections or other concurrent disease
  • Other malignant diseases within 5 years of inclusion in the study, except basal cell squamous cell carcinoma of the skin and cervical carcinoma-in-situ
  • Prior radiotherapy within 30 days of treatment start
  • Other experimental therapy within 30 days of treatment initiation
  • Patients who are breast feeding, childbearing or of childbearing potential without using dual effective contraception
  • Clinical or radiological evidence of CNS metastasis
  • Completed any major surgery, excision biopsy or significant traumatic lesion ≥ 4 weeks from start of treatment and completed any minor surgery ≥ 1 week prior to start of treatment

    • Insertion of a vascular access device is not considered major or minor surgery from the viewpoint of protocol eligibility
    • Patients must have fully recovered from the procedure and have a fully healed incision
  • Planned radiation therapy against target-lesions
  • Patients with significant non-healing wounds or ulcers
  • History or evidence of thrombotic or hemorrhagic disorders

    • Significant haemorrhage (> 30 ml/bleeding episode in previous 3 months)
    • Haemoptysis (> 5 ml fresh blood in previous 4 weeks)
  • Patients on full-dose anticoagulation (e.g., warfarin) are eligible provided that both of the following criteria are met:

    • The patient has an in-range INR (usually between 2 and 3) on a stable dose of oral anticoagulant or is on a stable dose of low molecular weight heparin
    • The patient has no active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
  • Previous Cerebro-Vascular Accident (CVA), Transient Ischemic Attack (TIA) or Sub-Arachnoid Hemorrhage (SAH) within 12 months prior to randomization
  • No known or history of HIV seropositivity
  • The use of ACE inhibitors is not permitted during the study
  • Known allergy to temsirolimus, sirolimus, polysorbate 80 or included agents.
  • Agents with strong CYP3A4-inhibitory potential
  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: NCT00827684

Locations
Denmark
Rigshospitalet, Department of Oncology
Copenhagen, Denmark, DK-2100
Vejle Hospital, Dept. of Oncology
Vejle, Denmark
Sponsors and Collaborators
Vejle Hospital
Investigators
Study Chair: Anders Jakobsen, MD, DMSc Vejle Hospital
Principal Investigator: Karen-Lise G Spindler, MD, PhD Vejle Hospital
  More Information

No publications provided

Responsible Party: Professor, MD, DMSc Andes Jakobsen, Dept. of Oncology, Vejle Hospital
ClinicalTrials.gov Identifier: NCT00827684     History of Changes
Other Study ID Numbers: 2008-007665-22
Study First Received: January 22, 2009
Last Updated: June 7, 2011
Health Authority: Denmark: Ethics Committee
Denmark: Danish Medicines Agency
Denmark: Danish Dataprotection Agency

Keywords provided by Vejle Hospital:
KRAS mutation

Additional relevant MeSH terms:
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Everolimus
Irinotecan
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses
Topoisomerase I Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on October 29, 2014