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

Sponsor

The Queen Elizabeth Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT01139138

Collaborator

Amgen (Industry), Novartis (Industry)

Enrollment

Location

Arm

Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer Colorectal Carcinoma Colorectal Tumors Neoplasms, Colorectal	Drug: Panitumumab Drug: Irinotecan Drug: Everolimus	Phase 1/Phase 2

Detailed 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

Study Design

Study Type:

Interventional

Actual Enrollment :

49 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase IB/II Study of Second Line Therapy With Panitumumab, Irinotecan and Everolimus (PIE) in Metastatic Colorectal Cancer With KRAS WT

Study Start Date :

Jun 1, 2010

Actual Primary Completion Date :

Aug 1, 2015

Actual Study Completion Date :

Jun 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Panitumumab + Irinotecan + Everolimus	Drug: Panitumumab Panitumumab 6mg/kg IV every 14 days Other Names: Vectibix Drug: Irinotecan Irinotecan 200mg/m2 IV every 14 days Drug: Everolimus Everolimus daily po (dosage varies with cohort) Other Names: RAD001

Arm

Intervention/Treatment

Experimental: Panitumumab + Irinotecan + Everolimus

Drug: Panitumumab

Panitumumab 6mg/kg IV every 14 days

Other Names:

Vectibix

Drug: Irinotecan

Irinotecan 200mg/m2 IV every 14 days

Drug: Everolimus

Everolimus daily po (dosage varies with cohort)

Other Names:

RAD001

Outcome Measures

Primary Outcome Measures

Dose limiting toxicities [at end of cycle 2 (each cycle is 14 days)]
To determine the maximum tolerated dose (MTD)of everolimus, irinotecan and panitumumab when given in combination for patients with Kras WT mCRC

Secondary Outcome Measures

Safety & toxicity [Approximately 24 weeks]
Safety and toxicity assessed weekly during the phase Ib component (as per NCI CTCAE version 3.0) and fortnightly during the phase II component
Response rate [Assessed every 6 weeks until disease progression]
Objective tumour response as per RECIST criteria V1.0
Progression free survival [Until disease progression, occurrence of new disease or death]
Overall Survival [Assessed 3 monthly until death]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.