None listed
Conditions
Brief summary
New approaches to the treatment of advanced oesophago-gastric cancer are likely to involve biologically relevant targets, which either alone or in combination with chemotherapy, may result in prolonged disease stabilisation or tumour response, hence improving patient outcomes (QOL, symptom control and survival). One such biological target is the epidermal growth factor receptor (EGFR). The role of EGFR in advanced oesophago-gastric cancer is unknown although high EGFR expression is known to occur in around 60-80% of patients and is associated with an adverse prognosis and resistance to chemotherapy. Furthermore, responses have been observed using agents targeting EGFR in advanced oesophago-gastric cancer. Cetuximab is a well-characterised, relatively non-toxic antibody directed against EGFR. Cetuximab has been used as a single agent and in combination with chemotherapy in a variety of cancers. Hence it seems appropriate to examine the role of cetuximab in advanced oesophago-gastric cancer. Considering the fact that docetaxel based regimens appear highly active in advanced oesophago-gastric cancer, there is a strong rationale for combining docetaxel with cetuximab. Synergy between taxanes and other agents targeting the family of EGFRs has been observed in other types of cancer. Therefore we have developed this Phase II study of cetuximab plus docetaxel in patients with advanced (recurrent or metastatic) oesophago-gastric cancer who are refractory to docetaxel therapy. This is an optional extension study for patients who have participated in ATTAX (AG0603) (all of whom receive docetaxel) and who have progressed either during or within 6 months of docetaxel based chemotherapy.
Interventions
Weekly docetaxel (30mg/m2 on day 1 and day 8 of a 3 week cycle) plus Cetuximab (initial dose 400mg/m2 over 2 hours followed by weekly doses of 250mg/m2). Treatment will continue for 8 cycles (24 weeks) or until tumour progression.
Sponsors
Australian Gastro-Intestinal Trials Group
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
a) Participation in the ATTAX studyb) Progression during ATTAX or within 6 months of docetaxel based chemotherapy as assessed using RECIST criteria.c) Consent has been provided for EGFR testing (any level of EGFR expression including EGFR negative tumours is allowed)d) WHO performance status of 0, 1 or 2 (Patients who are PS 2 should have serum albumin >30 g/L).e) Adequate bone marrow function with platelets > 100 X 109/l, and neutrophils > 1.5 X 109/l.f) Normal renal function, with serum creatinine <1.5x upper limit institutional normal range.g) Adequate hepatic function with serum total bilirubin < 1.25 X upper limit of normal range and ALT/AST <2.5x upper limit of normal range.h) No concurrent uncontrolled medical conditions.i) Negative pregnancy test and adequate contraceptive precautions if relevant.j) Written informed consent.
Exclusion criteria
a) Medical or psychiatric conditions that compromise the patient’s ability to give informed consent or comply with the study protocol.b) Metastatic disease to the central nervous system. If CNS metastases are suspected they should be fully investigated by CT scan, MRI scan or CSF cytology.c) Allergy or hypersensitivity to docetaxel.d) Pregnancy or breast feeding.e) Clinical evidence of >grade 2 peripheral neuropathy, ie. affecting activities of daily living.f) Clinically significant cardiac disease comprising recent myocardial infarction, unstable angina or cardiac failure.g) Participation in any investigational drug study within the previous 4 weeks, except for ATTAX.h) Previous exposure to EGFR-targeting therapy.
Outcome results
None listed