Dual Inhibition of EGFR Signalling Using the Combination of Cetuximab and Erlotinib (Dux)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2008 by Austin Health.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborators:
Ballarat Health Services
Queen Elizabeth Hospital, Adelaide
Royal North Shore Hospital
Information provided by:
Austin Health
ClinicalTrials.gov Identifier:
NCT00784667
First received: November 3, 2008
Last updated: November 29, 2010
Last verified: November 2008
  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 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Dual Inhibition of EGFR Signalling Using the Combination of Cetuximab (Erbitux) and Erlotinib (Tarceva) in Patients With Chemotherapy-refractory Colorectal Cancer

Resource links provided by NLM:


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: February 2011
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Cetuximab
    400mg/m2 intravenously week 1, then 250 mg/m2 weekly intravenously
    Other Name: Erbitux
    Drug: Erlotinib
    100mg orally daily continuously
    Other Name: Tarceva
  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
  • k-ras mutant tumours now excluded
  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: NCT00784667

Locations
Australia, New South Wales
Royal North Shore Hospital
Sydney, New South Wales, Australia
Australia, South Australia
Queen Elizabeth Hospital
Adelaide, South Australia, Australia
Australia, Victoria
Ballarat Base Hospital
Ballarat, Victoria, Australia
Austin Health
Melbourne, Victoria, Australia, 3084
Sponsors and Collaborators
Austin Health
Ballarat Health Services
Queen Elizabeth Hospital, Adelaide
Royal North Shore Hospital
  More Information

No publications provided

Responsible Party: Dr Niall Tebbutt, Austin Health
ClinicalTrials.gov Identifier: NCT00784667     History of Changes
Other Study ID Numbers: H2008/03282
Study First Received: November 3, 2008
Last Updated: November 29, 2010
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Austin Health:
Colorectal neoplasm
Metastasis

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Cetuximab
Erlotinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014