None listed
Conditions
Brief summary
The purpose of this study is to investigate the effectiveness of a combination of two drugs, called AMG 102 and panitumumab, for patients with brain tumours that have returned after previous treatment. In addition, the study will investigate the side-effects that might be associated with the combination of these two drugs when treating brain tumours. Research has shown that AMG 102 is effective at treating brain tumours in a small proportion of patients, and preliminary results in the laboratory show that panitumumab could make AMG 102 more effective at treating brain tumours. Therefore this study will be testing this combination of drugs. The combination of AMG 102 and panitumumab has previously been tested in 8 patients with bowel cancer, and is continuing to be tested in an ongoing bowel cancer study, but has not previously been tested in patients with brain tumours. Because very few patients have been treated with the combination of AMG 102 and panitumumab, the study will be conducted in two phases. Initially 3 patients will be treated at least one week apart. Once these 3 patients have completed 4 weeks of treatment each, and if there are no concerns with side effects, a further 3 patients will be treated at the same dose. If unacceptable side effects are observed, a lower dose will be tested, again treating 3 patients at least one week apart. If unacceptable side effects are still observed at the lower dose, an even lower dose will be tested. Using this system, the dose for the second phase will be identified, or if an acceptable dose cannot be identified, the study will not continue. A total of 6 to 18 patients will participate in the first phase of the study. The second phase of the study will enrol patients until a total of 42 patients have been treated at the dose identified in the first phase.
Interventions
All patients will receive both AMG 102 and panitumumab, administered by intravenous infusion on day 1 and day 15 of every 28 day treatment cycle, repeated for 6 cycles, unless stopped earlier due to disease progression or unacceptable toxicity. The doses to be used in the phase II component of the study will be determined in the phase I component of the study. The phase I will test doses of AMG 102 of 10 mg/kg and 5 mg/kg, and doses of panitumumab of 6 mg/kg and 4.8 mg/kg.
Sponsors
University of Sydney
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
1. Patients must have clinically or histologically proven recurrent supratentorial glioblastoma (Astrocytoma World Health Organisation (WHO) Grade IV, including GBM subtypes, e.g. gliosarcoma). 2. Measurable disease at either initial diagnosis or at recurrence. 3. >=18 years of age; 4. Tumour tissue specimens must be available; 5. Stable or decreasing dose of steroids for >=7 days prior to registration; 6. Patients must have had prior treatment with radiotherapy and temozolomide; 7. Phase I: Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1; Phase II: ECOG Performance Status 0-2; 8. Patients must have a mini-mental state examination (MMSE) of >=15; 9. Adequate hepatic, renal and bone marrow function; 10. Written informed consent must be obtained.
Exclusion criteria
1. Treatment with chemotherapy, biologic agents or anti-coagulants within 30 days prior to registration, or prior treatment with an anti-Epidermal Growth Factor Receptor (EGFR) agent at any time; 2. Have had any surgery or brain biopsy within 4 weeks prior to registration or who have not fully recovered from this intervention; 3. History of other malignancy; 4. History of coagulation disorder associated with bleeding; 5. Thrombosis or vascular ischemic events within one year prior to registration; 6. Concurrent illness; 7. Inability to undergo Gd-MRI; 8. Clinically significant cardiovascular disease within one year prior to registration; 9. History of interstitial lung disease.
Outcome results
None listed