Dual Inhibition of EGFR Signalling Using the Combination of Cetuximab and Erlotinib - Full Text View

Sponsors and Collaborators:	Austin Health Ballarat Health Services Queen Elizabeth Hospital, Adelaide Royal North Shore Hospital, Sydney
Information provided by:	Austin Health
ClinicalTrials.gov Identifier:	NCT00784667

Purpose

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.

Condition	Intervention	Phase
Metastatic Colorectal Cancer	Drug: Cetuximab Drug: Erlotinib	Phase II

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Erlotinib Erlotinib hydrochloride Cetuximab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Efficacy Study
Official Title:	Dual Inhibition of EGFR Signalling Using the Combination of Cetuximab (Erbitux) and Erlotinib (Tarceva) in Patients With Chemotherapy-Refractory Colorectal Cancer

Further study details as provided by Austin Health:

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 [ Time Frame: 6 weekly ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Toxicity [ Time Frame: Weekly ] [ Designated as safety issue: Yes ]
Progression free survival [ Time Frame: 6 weekly ] [ Designated as safety issue: No ]
Overall survival [ Time Frame: Weekly ] [ Designated as safety issue: No ]

Estimated Enrollment:	50
Study Start Date:	October 2008
Estimated Study Completion Date:	July 2010
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Intervention Details:

400mg/m2 intravenously week 1, then 250 mg/m2 weekly intravenously

100mg orally daily continuously

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
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00784667

Contacts

Contact: Niall C Tebbutt, BM BCh PhD

+61 3 9496 5763

niall.tebbutt@ludwig.edu.au

Locations

Australia, New South Wales
Royal North Shore Hospital	Not yet recruiting
Sydney, New South Wales, Australia
Principal Investigator: Nick Pavlakis, MBBS FRACP
Australia, South Australia
Queen Elizabeth Hospital	Not yet recruiting
Adelaide, South Australia, Australia
Principal Investigator: Timothy Price, MBBS FRACP
Australia, Victoria
Austin Health	Recruiting
Melbourne, Victoria, Australia, 3084
Principal Investigator: Niall C Tebbutt, BM BCh PhD FRACP
Ballarat Base Hospital	Not yet recruiting
Ballarat, Victoria, Australia
Principal Investigator: Geoffrey Chong, MBBS FRACP

Sponsors and Collaborators

Austin Health

Ballarat Health Services

Queen Elizabeth Hospital, Adelaide

Royal North Shore Hospital, Sydney

More Information

Responsible Party:	Austin Health ( Dr Niall Tebbutt )
Study ID Numbers:	H2008/03282
Study First Received:	November 3, 2008
Last Updated:	November 3, 2008
ClinicalTrials.gov Identifier:	NCT00784667
Health Authority:	Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Austin Health:

Colorectal neoplasm
Metastasis

Study placed in the following topic categories:

Erlotinib
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Cetuximab
Colonic Diseases

Neoplasm Metastasis
Gastrointestinal Neoplasms
Intestinal Diseases
Rectal Diseases
Intestinal Neoplasms
Colorectal Neoplasms

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Site
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

Therapeutic Uses
Enzyme Inhibitors
Protein Kinase Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009