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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00784667




Registration number
NCT00784667
Ethics application status
Date submitted
3/11/2008
Date registered
4/11/2008
Date last updated
30/11/2010

Titles & IDs
Public title
Dual Inhibition of EGFR Signalling Using the Combination of Cetuximab and Erlotinib
Scientific title
Dual Inhibition of EGFR Signalling Using the Combination of Cetuximab (Erbitux) and Erlotinib (Tarceva) in Patients With Chemotherapy-refractory Colorectal Cancer
Secondary ID [1] 0 0
H2008/03282
Universal Trial Number (UTN)
Trial acronym
Dux
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Colorectal Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cetuximab
Treatment: Drugs - Erlotinib

Treatment: Drugs: Cetuximab
400mg/m2 intravenously week 1, then 250 mg/m2 weekly intravenously

Treatment: Drugs: Erlotinib
100mg orally daily continuously
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
6 weekly
Secondary outcome [1] 0 0
Toxicity
Timepoint [1] 0 0
Weekly
Secondary outcome [2] 0 0
Progression free survival
Timepoint [2] 0 0
6 weekly
Secondary outcome [3] 0 0
Overall survival
Timepoint [3] 0 0
Weekly

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
UNKNOWN
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/10/2008
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/02/2011
Actual
Sample size
Target
50
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Royal North Shore Hospital - Sydney
Recruitment hospital [2] 0 0
Queen Elizabeth Hospital - Adelaide
Recruitment hospital [3] 0 0
Ballarat Base Hospital - Ballarat
Recruitment hospital [4] 0 0
Austin Health - Melbourne
Recruitment postcode(s) [1] 0 0
- Sydney
Recruitment postcode(s) [2] 0 0
- Adelaide
Recruitment postcode(s) [3] 0 0
- Ballarat
Recruitment postcode(s) [4] 0 0
3084 - Melbourne

Funding & Sponsors
Primary sponsor type
Government body
Name
Austin Health
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Ballarat Health Services
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Queen Elizabeth Hospital, Adelaide
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Royal North Shore Hospital
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00784667
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00784667