Glioblastoma MedDRA version: 13.1 Level: PT Classification code 10018336 Term: Glioblastoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Cediranib
Product Code: AZD2171
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Cediranib
CAS Number: 288383-
Sponsors
Joint UCLH and UCL Biomedical Research Unit
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Provision of informed consent • Age =18 years • Life expectancy = 12 weeks • Histological/cytological confirmation of glioblastoma (WHO grade IV) • Patients with measurable disease (contrast-enhancing tumour =10 mm by shortest diameter on 2 axial slices) by MRI imaging within 7 days prior to enrolment. (If patients have recently had a routine MRI scan, this should be assessed before deciding whether or not to screen the patient, and booking the screening/baseline MRI.) • Patients must have been on no steroids or a stable dose of steroids (dexamethasone) for at least 5 days before the baseline MRI • Patients must have completed standard first-line treatment for glioblastoma including surgery (with exception, if patient does not receive surgery as part of first-line treatment due to anatomical location, based on neurosurgeon’s assessment), cranial radiotherapy and chemotherapy with concomitant temozolomide. It is not essential that the entire Stupp regimen of 6 cycles of adjuvant temozolomide following chemoradiotherapy has been completed. The last dose of temozolomide must be more than 28 days from enrolment. Gliadel® wafers are permitted, as it is part of local treatment. No other previous treatment for glioblastoma is permitted (other than steroids). • Patients must have a Karnofsky Performance Score of 70 or above • Patients must have a mini-mental status examination score of 15 or greater • Patients who require either oral anticoagulants (coumadin, warfarin) or low molecular weight heparin are eligible provided there is increased vigilance with respect to monitoring INR. For inclusion in this genetic research, patients must fulfil the following criterion: • Provision of informed consent for genetic research (separate consent required for tumour biopsy, blood sample, and post mortem donations) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Patients on enzyme-inducing anti-epileptic drugs within 2 weeks prior to study enrolment. Note: Patients are eligible if they switched to non-enzyme inducing agents and discontinued enzyme-inducing agents for more than or equal to 2 weeks prior to randomisation • Inadequate bone marrow reserve as demonstrated by an absolute neutrophil count =1.5 x 109 /L or platelet count =100 x 109 /L or requiring regular blood transfusions to maintain haemoglobin >9g/dL • Serum bilirubin =1.5 x ULRR (Upper Limit of the Reference Range)(except for patients with known documented cases of Gilbert’s Syndrome) • ALT or AST =5 x ULRR • Serum creatinine >1.5 x ULRR or a creatinine clearance of =50mL/min calculated by Cockcroft-Gault • Greater than +1 proteinuria on two consecutive dipsticks taken no less than 1 week apart unless urinary protein 150/100mmHg in the presence or absence of a stable regimen of anti-hypertensive therapy, or patients who are requiring maximal doses of calcium channel blockers to stabilise blood pressure • Any evidence of severe or uncontrolled diseases (e.g. unstable or uncompensated respiratory, cardiac, hepatic or renal disease) • Unresolved toxicity >CTC AE grade 1 from previous anti-cancer therapy (including radiotherapy) except alopecia (if applicable) • Mean QTc with Bazetts correction >470msec in screening ECG or history of familial, long QT syndrome • Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy • Significant haemorrhage (>30mL bleeding/episode in previous 3 months) or haemoptysis (>5mL fresh blood in previous 4 weeks) • Recent (<14 days) major surgery or brain biopsy. Recent craniotomy (<28 days) prior to first dose, or a surgical incision that is not fully healed • Pregnant or breast-feeding women or women of childbearing potential with a positive pregnancy test prior to receiving study medication • Known hypersensitivity to cediranib, gefitinib or any of its excipients • History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ) within 5 years, unless the patient has been disease free for 2 years and they have tissue diagnosis of the target lesion • Known infection with hepatitis B or C or HIV • Involvement in the planning and conduct of the study (applies to both UCL CTC, AstraZeneca staff and staff at the study site) • Past medical history of interstitial lung disease, idiopathic pulmonary fibrosis, drug-induced interstitial disease, radiation pneumonitis which required steroid treatment or any evidence of clinically active interstitial lung disease • Previous enrolment as part of the present study • Treatment with an investigational drug within 30 days prior to the first dose of cediranib/gefitinib
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy of cediranib in combination with oral gefitinib with cediranib alone. The primary outcome variable will be progression free survival as defined as the date from randomisation to the date of first progression or death due to any cause, whichever one comes first.; Secondary Objective: • To document the safety and tolerability of cediranib in combination with oral gefitinib and cediranib alone. • To compare cediranib in combination with oral gefitinib and cediranib alone in terms of steroid sparing effects • To document the quality of life and neurological symptoms reported by patients taking cediranib in combination with oral gefitinib and cediranib alone. • To investigate the relationship between the effects of cediranib (+/- gefitinib) on levels of soluble angiogenesis biomarkers and clinical efficacy • To investigate the relationship between the patient’s genetic profile and efficacy of cediranib (+/- gefitinib) ; Primary end point(s): Progression free survival (PFS) defined as the time from the date of randomisation to the date of first progression or death due to any cause, whichever one comes first. Progression will be determined using site determination of performance status and a central review of the MRI scans, and by working to a modified version of the RANO criteria (Response Assessment in Neuro-oncology), see Wen et al 2010, as described in the protocol. Wen PY, Macdonald DR, Reardon DA et al. Updated response criteria for highgrade gliomas: response assessment in neurooncology working group. J Clinical Oncology 2010: 28: 19631972 | — |
Countries
United Kingdom
Outcome results
None listed