Back to resultsDual Inhibition of EGFR Signalling Using the Combination of Cetuximab and Erlotinib (Dux)
Primary Purpose
Metastatic Colorectal Cancer
Status
Unknown status
Phase
Phase 2
Locations
Australia
Study Type
Interventional
Intervention
Cetuximab
Erlotinib
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Colorectal Cancer focused on measuring Colorectal neoplasm, Metastasis
Eligibility Criteria
Inclusion Criteria:
- Age>18 years
- Histological diagnosis of colorectal cancer
- Metastatic disease not amenable to resection
- Measurable disease as assessed by CT scan using RECIST criteria
- Received and failed fluoropyrimidine therapy, where failure is defined as radiological progression after therapy for metastatic disease, prior adjuvant therapy, or toxicity limiting further therapy
- Received and failed oxaliplatin therapy, where failure is defined as radiological progression after therapy for metastatic disease, prior adjuvant therapy ,or toxicity (including neuro-toxicity) limiting further therapy
- Received and failed irinotecan therapy, where failure is defined as radiological progression after therapy for metastatic disease or toxicity limiting further therapy
- ECOG PS 0-1
- Adequate bone marrow function with platelets > 100 X 109/l; neutrophils > 1.5 X 109/l
- Adequate renal function, with calculated creatinine clearance >40 ml/min (Cockcroft and Gault).
- 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)
- Life expectancy of at least 12 weeks
- No other concurrent uncontrolled medical conditions
- No other malignant disease apart from non-melanotic skin cancer or carcinoma in situ of the uterine cervix or any other cancer treated with curative intent >2 years previously without evidence of relapse
- Women and partners of women of childbearing potential must agree to use adequate contraception
- Written informed consent including consent for biomarker studies
Exclusion Criteria:
- 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
- Participation in any investigational drug study within the previous 4 weeks
- Patients with uncontrolled clinically significant cardiac disease, arrhythmias or angina pectoris
- Untreated CNS metastases
- Pregnancy or lactation
- k-ras mutant tumours now excluded
Sites / Locations
- Royal North Shore Hospital
- Queen Elizabeth Hospital
- Ballarat Base Hospital
- Austin Health
Outcomes
Primary Outcome Measures
To determine the response rate (RECIST criteria). Responses will be evaluated for the whole patient group and separately for k-ras wild-type and k-ras mutant tumours
Secondary Outcome Measures
Toxicity
Progression free survival
Overall survival
Full Information
NCT ID
NCT00784667
First Posted
November 3, 2008
Last Updated
November 29, 2010
Sponsor
Austin Health
Collaborators
Ballarat Health Services, Queen Elizabeth Hospital, Adelaide, Royal North Shore Hospital
1. Study Identification
Unique Protocol Identification Number
NCT00784667
Brief Title
Dual Inhibition of EGFR Signalling Using the Combination of Cetuximab and Erlotinib
Acronym
Dux
Official Title
Dual Inhibition of EGFR Signalling Using the Combination of Cetuximab (Erbitux) and Erlotinib (Tarceva) in Patients With Chemotherapy-refractory Colorectal Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
November 2008
Overall Recruitment Status
Unknown status
Study Start Date
October 2008 (undefined)
Primary Completion Date
January 2010 (Actual)
Study Completion Date
February 2011 (Anticipated)
3. Sponsor/Collaborators
Name of the Sponsor
Austin Health
Collaborators
Ballarat Health Services, Queen Elizabeth Hospital, Adelaide, Royal North Shore Hospital
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a clinical trial investigating the effectiveness and safety of the combination of the study drugs cetuximab and erlotinib in patients with advanced (metastatic) refractory colorectal (bowel) cancer. If bowel cancer has spread to other organs (metastatic colorectal cancer), it is usually incurable and life-expectancy without treatment is less then 6 months on average. Currently, chemotherapy has been shown to have a significant impact in advanced colorectal cancer in terms of maintenance of quality of life and extension of survival. However, ultimately tumours will develop resistance to chemotherapy. Treatment options and subsequent survival at that stage are very limited. Therefore, new therapeutic approaches are urgently needed.
It is common for colorectal cancer cells to contain growth receptors, like antennae, on their surface which regulate their growth. The drugs used in this trial have been shown to be effective in targeting one of these growth receptors; the epidermal growth factor receptor (EGFR). Cetuximab is an antibody (protein produced by the immune system involved in the defense of the body against infections) against EGFR. Cetuximab has been shown to improve the survival of patients with chemotherapy refractory advanced colorectal cancer. Erlotinib is a protein that prevents activation and hence signaling by EGFR. Erlotinib improves survival in patients with advanced lung cancer. Although, each of these drugs are known to be effective at inhibiting EGFR when they are given alone, at least in some cases, it is hoped that using two drugs that target the same receptor pathway in different ways will provide a more effective treatment.
50 patients from four hospitals in Australia will participate in this trial, with approximately 25 patients being enrolled at Austin Health. All participants will receive the same treatment.
Neither of the study drugs are chemotherapy, and hence it is expected that the treatment would be well tolerated. The most frequent side effect associated with EGFR inhibitors is skin rash. Other possible side effects are diarrhea and low magnesium levels.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer
Keywords
Colorectal neoplasm, Metastasis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
50 (Anticipated)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
Cetuximab
Other Intervention Name(s)
Erbitux
Intervention Description
400mg/m2 intravenously week 1, then 250 mg/m2 weekly intravenously
Intervention Type
Drug
Intervention Name(s)
Erlotinib
Other Intervention Name(s)
Tarceva
Intervention Description
100mg orally daily continuously
Primary Outcome Measure Information:
Title
To determine the response rate (RECIST criteria). Responses will be evaluated for the whole patient group and separately for k-ras wild-type and k-ras mutant tumours
Time Frame
6 weekly
Secondary Outcome Measure Information:
Title
Toxicity
Time Frame
Weekly
Title
Progression free survival
Time Frame
6 weekly
Title
Overall survival
Time Frame
Weekly
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
Metastatic disease not amenable to resection
Measurable disease as assessed by CT scan using RECIST criteria
Received and failed fluoropyrimidine therapy, where failure is defined as radiological progression after therapy for metastatic disease, prior adjuvant therapy, or toxicity limiting further therapy
Received and failed oxaliplatin therapy, where failure is defined as radiological progression after therapy for metastatic disease, prior adjuvant therapy ,or toxicity (including neuro-toxicity) limiting further therapy
Received and failed irinotecan therapy, where failure is defined as radiological progression after therapy for metastatic disease or toxicity limiting further therapy
ECOG PS 0-1
Adequate bone marrow function with platelets > 100 X 109/l; neutrophils > 1.5 X 109/l
Adequate renal function, with calculated creatinine clearance >40 ml/min (Cockcroft and Gault).
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)
Life expectancy of at least 12 weeks
No other concurrent uncontrolled medical conditions
No other malignant disease apart from non-melanotic skin cancer or carcinoma in situ of the uterine cervix or any other cancer treated with curative intent >2 years previously without evidence of relapse
Women and partners of women of childbearing potential must agree to use adequate contraception
Written informed consent including consent for biomarker studies
Exclusion Criteria:
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
Participation in any investigational drug study within the previous 4 weeks
Patients with uncontrolled clinically significant cardiac disease, arrhythmias or angina pectoris
Untreated CNS metastases
Pregnancy or lactation
k-ras mutant tumours now excluded
Facility Information:
Facility Name
Royal North Shore Hospital
City
Sydney
State/Province
New South Wales
Country
Australia
Facility Name
Queen Elizabeth Hospital
City
Adelaide
State/Province
South Australia
Country
Australia
Facility Name
Ballarat Base Hospital
City
Ballarat
State/Province
Victoria
Country
Australia
Facility Name
Austin Health
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
12. IPD Sharing Statement
Learn more about this trial
Dual Inhibition of EGFR Signalling Using the Combination of Cetuximab and Erlotinib
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