Safety Study of the Combination of Panitumumab, Irinotecan and Everolimus in the Treatment of Advanced Colorectal Cancer

• Status: Completed
• Trial end date: 2017-06-01
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: The Queen Elizabeth Hospital
• Collaborators: Amgen; Novartis
• Treatments: Antibodies, Monoclonal; Camptothecin; Everolimus; Irinotecan; Panitumumab; Sirolimus

Criteria

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.