Safety Study of the Combination of Panitumumab, Irinotecan and Everolimus in the Treatment of Advanced Colorectal Cancer (PIE)
Verified November 2014 by The Queen Elizabeth Hospital
Information provided by (Responsible Party):
Amanda Townsend, The Queen Elizabeth Hospital
First received: May 28, 2010
Last updated: November 3, 2014
Last verified: November 2014
This study will assess the safety of panitumumab, irinotecan and everolimus when given in combination to treat advanced colorectal cancer
||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||A Phase IB/II Study of Second Line Therapy With Panitumumab, Irinotecan and Everolimus (PIE) in Metastatic Colorectal Cancer With KRAS WT
Primary Outcome Measures:
Secondary Outcome Measures:
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||June 2015 (Final data collection date for primary outcome measure)
Experimental: Panitumumab + Irinotecan + Everolimus
Panitumumab 6mg/kg IV every 14 days
Other Name: Vectibix
Irinotecan 200mg/m2 IV every 14 days
Everolimus daily po (dosage varies with cohort)
Other Name: RAD001
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
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- 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
- 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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01139138
|The Queen Elizabeth Hospital
|Adelaide, South Australia, Australia, 5011 |
|Contact: Pamela Cooper 08 8222 8009 |
The Queen Elizabeth Hospital
||Amanda Townsend, MBBS
||Queen Elizabeth Hospital
No publications provided
||Amanda Townsend, Dr, The Queen Elizabeth Hospital
History of Changes
|Other Study ID Numbers:
|Study First Received:
||May 28, 2010
||November 3, 2014
||Australia: Human Research Ethics Committee
Australia: Department of Health and Ageing Therapeutic Goods Administration
Australia: National Health and Medical Research Council
Keywords provided by The Queen Elizabeth Hospital:
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on October 07, 2015
Digestive System Diseases
Digestive System Neoplasms
Neoplasms by Site
Antineoplastic Agents, Phytogenic
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Topoisomerase I Inhibitors