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

• Status: Completed
• Trial end date: 2011-06-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Vejle Hospital
• Treatments: Camptothecin; Everolimus; Irinotecan; Sirolimus

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