Overview

This trial is active, not recruiting.

Conditions colorectal cancer, colorectal carcinoma, colorectal tumors, neoplasms, colorectal
Treatments panitumumab, irinotecan, everolimus
Phase phase 1/phase 2
Targets EGFR, mTOR, FKBP-12
Sponsor The Queen Elizabeth Hospital
Collaborator Amgen
Start date June 2010
End date August 2015
Trial size 49 participants
Trial identifier NCT01139138, AU-2009-0003/CRAD001CAU06T

Summary

This study will assess the safety of panitumumab, irinotecan and everolimus when given in combination to treat advanced colorectal cancer

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
panitumumab Vectibix
Panitumumab 6mg/kg IV every 14 days
irinotecan
Irinotecan 200mg/m2 IV every 14 days
everolimus RAD001
Everolimus daily po (dosage varies with cohort)

Primary Outcomes

Measure
Dose limiting toxicities
time frame: at end of cycle 2 (each cycle is 14 days)

Secondary Outcomes

Measure
Safety & toxicity
time frame: Approximately 24 weeks
Response rate
time frame: Assessed every 6 weeks until disease progression
Progression free survival
time frame: Until disease progression, occurrence of new disease or death
Overall Survival
time frame: Assessed 3 monthly until death

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Age > 18 years - Histological diagnosis of colorectal cancer that is KRAS wild type - Metastatic disease not amenable to resection - Measurable disease as assessed by CT scan using RECIST criteria - Received and failed fluoropyrimidine therapy - Radiographically documented disease progression per RECIST criteria - For phase 1b group only, ECOG PS 0-1 - For phase 2 group only, ECOG PS 0-2 - Adequate bone marrow function with haemoglobin > 100 g/L, platelets > 100 X 109/l; neutrophils > 1.5 X 109/l within 7 days of enrolment - Adequate renal function, with calculated creatinine clearance >40 ml/min (Cockcroft and Gault) within 7 days of enrolment - Adequate hepatic function with serum total bilirubin < 1.25 X upper limit of normal range and ALT or AST<2.5xULN (<5xULN if liver metastases present) within 7 days of enrolment - Magnesium ≥ lower limit of normal within 7 days of enrolment. - Fasting serum cholesterol ≤ 7.75mmol/L AND fasting triglycerides ≤ 2.5 x ULN. Note: In case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication. - Life expectancy of at least 12 weeks - Negative pregnancy test ≤ 72 hours before commencing study treatment (women of childbearing potential only). - Written informed consent including consent for biomarker studies Exclusion Criteria: - Presence of KRAS mutation in tumour sample - For Phase 1b group only, patients with prior pelvic radiotherapy. - Systemic chemotherapy, immunotherapy, approved proteins/antibodies or any investigational agent within 4 weeks prior to commencing study treatment - Radiotherapy within 14 days of commencing study treatment. - Unresolved toxicities from prior systemic therapy or radiotherapy - Medical or psychiatric conditions that compromise the patient's ability to give informed consent or to complete the protocol - Prior treatment with drugs targeting EGFR such as cetuximab, panitumumab or erlotinib - Prior therapy with mTOR inhibitors (sirolimus, temsirolimus, everolimus) - Prior therapy with irinotecan - CYP3A4 enzyme inducing anti-convulsant medication ≤ 14 days prior to study treatment. - Ketoconazole ≤ 7 days before study treatment. - Uncontrolled diabetes mellitus defined by fasting glucose >1.5 x ULN. - Known cirrhosis, chronic active hepatitis, or chronic persistent hepatitis - Patients with known interstitial lung disease or severely impaired lung function - Patients with active bleeding diatheses. - Any uncontrolled clinically significant cardiac disease, arrhythmias or angina pectoris - Active inflammatory bowel disease or other bowel disease causing chronic diarrhoea - Chronic treatment with immunosuppressives - Patients with a known history of HIV seropositivity - Patients who have any severe and/or uncontrolled medical conditions or infections - Untreated or symptomatic CNS metastases - Patients who have a history of another primary malignant disease - Pregnancy or lactation. - Women and partners of women of childbearing potential who are not using effective contraception.

Additional Information

Official title A Phase IB/II Study of Second Line Therapy With Panitumumab, Irinotecan and Everolimus (PIE) in Metastatic Colorectal Cancer With KRAS WT
Principal investigator Amanda Townsend, MBBS
Description This is an open label uncontrolled phase IB/II study to determine the maximum tolerated dose (MTD) and assess the efficacy of everolimus, irinotecan and panitumumab when given in combination for patients with metastatic colorectal cancer and KRAS wild-type (WT). Patients with metastatic colorectal cancer (mCRC) that have failed fluorouracil based first line therapy will be included. It is anticipated that approximately 50 patients will be enrolled over a period of 24 months
Trial information was received from ClinicalTrials.gov and was last updated in February 2016.
Information provided to ClinicalTrials.gov by The Queen Elizabeth Hospital.