Safety Study of the Combination of Panitumumab, Irinotecan and Everolimus in the Treatment of Advanced Colorectal Cancer (PIE)
Primary Purpose
Colorectal Cancer, Colorectal Carcinoma, Colorectal Tumors
Status
Completed
Phase
Phase 1
Locations
Australia
Study Type
Interventional
Intervention
Panitumumab
Irinotecan
Everolimus
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer focused on measuring Colorectal Cancer, Colorectal Carcinoma, Colorectal Tumors, Neoplasms, Colorectal
Eligibility 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.
Sites / Locations
- The Queen Elizabeth Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Panitumumab + Irinotecan + Everolimus
Arm Description
Outcomes
Primary Outcome Measures
Dose limiting toxicities
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
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
Objective tumour response as per RECIST criteria V1.0
Progression free survival
Overall Survival
Full Information
NCT ID
NCT01139138
First Posted
May 28, 2010
Last Updated
November 2, 2017
Sponsor
The Queen Elizabeth Hospital
Collaborators
Amgen, Novartis
1. Study Identification
Unique Protocol Identification Number
NCT01139138
Brief Title
Safety Study of the Combination of Panitumumab, Irinotecan and Everolimus in the Treatment of Advanced Colorectal Cancer
Acronym
PIE
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 Type
Interventional
2. Study Status
Record Verification Date
November 2017
Overall Recruitment Status
Completed
Study Start Date
June 2010 (undefined)
Primary Completion Date
August 2015 (Actual)
Study Completion Date
June 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The Queen Elizabeth Hospital
Collaborators
Amgen, Novartis
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study will assess the safety of panitumumab, irinotecan and everolimus when given in combination to treat advanced colorectal cancer
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer, Colorectal Carcinoma, Colorectal Tumors, Neoplasms, Colorectal
Keywords
Colorectal Cancer, Colorectal Carcinoma, Colorectal Tumors, Neoplasms, Colorectal
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
49 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Panitumumab + Irinotecan + Everolimus
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Panitumumab
Other Intervention Name(s)
Vectibix
Intervention Description
Panitumumab 6mg/kg IV every 14 days
Intervention Type
Drug
Intervention Name(s)
Irinotecan
Intervention Description
Irinotecan 200mg/m2 IV every 14 days
Intervention Type
Drug
Intervention Name(s)
Everolimus
Other Intervention Name(s)
RAD001
Intervention Description
Everolimus daily po (dosage varies with cohort)
Primary Outcome Measure Information:
Title
Dose limiting toxicities
Description
To determine the maximum tolerated dose (MTD)of everolimus, irinotecan and panitumumab when given in combination for patients with Kras WT mCRC
Time Frame
at end of cycle 2 (each cycle is 14 days)
Secondary Outcome Measure Information:
Title
Safety & toxicity
Description
Safety and toxicity assessed weekly during the phase Ib component (as per NCI CTCAE version 3.0) and fortnightly during the phase II component
Time Frame
Approximately 24 weeks
Title
Response rate
Description
Objective tumour response as per RECIST criteria V1.0
Time Frame
Assessed every 6 weeks until disease progression
Title
Progression free survival
Time Frame
Until disease progression, occurrence of new disease or death
Title
Overall Survival
Time Frame
Assessed 3 monthly until death
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Amanda Townsend, MBBS
Organizational Affiliation
The Queen Elizabeth Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Queen Elizabeth Hospital
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5011
Country
Australia
12. IPD Sharing Statement
Learn more about this trial
Safety Study of the Combination of Panitumumab, Irinotecan and Everolimus in the Treatment of Advanced Colorectal Cancer
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