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

This is an interventional treatment trial for Metastatic Colorectal Cancer focused on measuring KRAS mutation Read More

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