Glioblastoma - a primary brain tumour MedDRA version: 9.1 Level: LLT Classification code 10018337 Term: Glioblastoma multiforme
Conditions
Interventions
Product Name: cediranib
Product Code: AZD2171
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: cediranib
CAS Number: 288383-20-0
Current Sponsor code: AZD2171
Concentration unit: mg millig
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of informed consent 2. Age =18 years 3. Life expectancy = 12 weeks 4. Histological/cytological confirmation of glioblastoma 5. Patients with measurable disease (contrast-enhancing tumour =10 mm by shortest diameter on 2 axial slices) by MRI imaging within 4 weeks prior to enrolment (Visit 1). Or patients who have undergone a resection without measurable disease prior to enrolment. 6. Patients must have been on no steroids or a stable dose of steroids for at least 5 days before the baseline MRI (Visit 2) 7. Patients must have failed standard frontline treatment for glioblastoma including surgery (with exception, if patient does not receive surgery as part of frontline treatment due to anatomical location, based on neurosurgeon’s assessment), cranial radiotherapy and chemotherapy with temozolomide. The last dose of temozolomide must be more than 28 days from randomization. Gliadel® wafers are permitted, if it is part of local treatment. 8. Patients must have a Karnofsky Performance Score of 70 or above 9. Patients must have a mini-mental status examination score of 15 or greater 10. 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. 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: 1. Patients on enzyme-inducing anti-epileptic drugs within 2 weeks prior to randomisation. - 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. 2. 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 3. Serum bilirubin = 1.5 x ULRR (except for patients with known documented cases of Gilbert’s Syndrome) 4. ALT or AST = 2.5 x ULRR. 5. Serum creatinine > 1.5 x ULRR or a creatinine clearance of = 50mL/min calculated by Cockcroft-Gault 6. 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. 9. Any evidence of severe or uncontrolled diseases (eg, unstable or uncompensated respiratory, cardiac, hepatic or renal disease) 10. Unresolved toxicity > CTCAE grade 1 from previous anti-cancer therapy (including radiotherapy) except alopecia (if applicable) 11. Mean QTc with Bazetts correction >470msec in screening ECG or history of familial, long QT syndrome 12. Significant haemorrhage (>30mL bleeding/episode in previous 3 months) or haemoptysis (>5mL fresh blood in previous 4 weeks) 13. Recent (<14 days) major thoracic or abdominal surgery or brain biopsy. Recent craniotomy(<28 days) prior to first dose, or a surgical incision that is not fully healed. 14. Pregnant or breast-feeding women or women of childbearing potential with a positive pregnancy test prior to receiving study medication 15. Known hypersensitivity to cediranib or any of its excipients 16. 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. 17. Known infection with hepatitis B or C or HIV 18. Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or staff at the study site) 19. Previous enrolment or randomisation of treatment in the present study. 20. Treatment with an investigational drug within 30 days prior to the first dose of cediranib 21. Other concomitant anti-cancer therapy except steroids 22. Previous anti-angiogenesis (eg bevacizumab, sorafenib, sunitinib) therapy 23. Patients with evidence of any intratumoral or peritumoral haemorrhage deemed significant by the treating physician 24. Patients who have received any form of cranial radiation within 3 months prior to study entry. 25. Known hypersensitivity to lomustine or any of its excipients 26. Patients with a baseline below 70% of the predicted Forced Vital Capacity (FVC) or Carbon Monoxide Diffusing Capacity (DLCO). However, patients with values less than these for either FVC or DLCO may still be eligible for enrolment provided that lung pathology has been excluded after
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to determine the relative efficacy of cediranib (either in monotherapy or in combination with oral lomustine ) compared to oral lomustine alone by assessment of progression free survival (PFS) as assessed by independent radiographic radiological review.;Secondary Objective: 1. To determine the relative efficacy of cediranib (either in monotherapy or in combination with oral lomustine) compared to oral lomustine alone by assessment of Overall Survival (OS) 2. To determine the relative efficacy of cediranib (either in monotherapy or in combination with oral lomustine) compared to oral lomustine alone by assessment of radiographic Response Rate (RR). 3. To determine the relative efficacy of cediranib (either in monotherapy or in combination with oral lomustine ) compared to oral lomustine alone by assessment of alive and progression free rate at 6 months defined as 24 weeks (APF6), after randomisation 4. To determine the steroid sparing effects of cediranib (either in monotherapy or in combination with oral lomustine) compared to oral lomustine alone by assessment of average daily steroid dosage change from baseline until progression and average number of progression/steroid free days. ;Primary end point(s): The primary outcome variable is PFS. The end of study is defined as the date when 270 subjects have died. | — |
Countries
Austria, Belgium, Czech Republic, France, Germany, Netherlands, United Kingdom
Outcome results
None listed