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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2011 by The Queen Elizabeth Hospital
Sponsor:
Collaborators:
Amgen
Novartis
Information provided by:
The Queen Elizabeth Hospital
ClinicalTrials.gov Identifier:
NCT01139138
First received: May 28, 2010
Last updated: August 4, 2011
Last verified: July 2011
  Purpose

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


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

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by The Queen Elizabeth Hospital:

Primary Outcome Measures:
  • Dose limiting toxicities [ Time Frame: at end of cycle 2 (each cycle is 14 days) ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Approximately 24 weeks ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Assessed every 6 weeks until disease progression ] [ Designated as safety issue: No ]
    Objective tumour response as per RECIST criteria V1.0

  • Progression free survival [ Time Frame: Until disease progression, occurrence of new disease or death ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: Assessed 3 monthly until death ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: June 2010
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Panitumumab + Irinotecan + Everolimus Drug: Panitumumab
Panitumumab 6mg/kg IV every 14 days
Other Name: Vectibix
Drug: Irinotecan
Irinotecan 200mg/m2 IV every 14 days
Drug: Everolimus
Everolimus daily po (dosage varies with cohort)
Other Name: RAD001

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 WT. Patients with metastatic colorectal cancer that have failed 5FU and oxaliplatin will be included. It is anticipated that approximately 50 patients will be enrolled over a period of 12 months

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  • Received and failed oxaliplatin 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.
  Contacts and Locations
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

Contacts
Contact: Pam Cooper +61 88222 7411 pamela.cooper@health.sa.gov.au
Contact: Amanda Townsend, MBBS +61 88222 7096 amanda.townsend@health.sa.gov.au

Locations
Australia, South Australia
The Queen Elizabeth Hospital Recruiting
Adelaide, South Australia, Australia, 5011
Contact: Louise Pirc    08 8222 7411      
Sponsors and Collaborators
The Queen Elizabeth Hospital
Amgen
Novartis
Investigators
Principal Investigator: Amanda Townsend, MBBS Queen Elizabeth Hospital
  More Information

No publications provided

Responsible Party: Dr Amanda Townsend, The Queen Elizabeth Hospital
ClinicalTrials.gov Identifier: NCT01139138     History of Changes
Other Study ID Numbers: AU-2009-0003/CRAD001CAU06T
Study First Received: May 28, 2010
Last Updated: August 4, 2011
Health Authority: 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:
Colorectal Cancer
Colorectal Carcinoma
Colorectal Tumors
Neoplasms, Colorectal

Additional relevant MeSH terms:
Colorectal Neoplasms
Carcinoma
Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Rectal Diseases
Antibodies, Monoclonal
Everolimus
Irinotecan
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 21, 2014