Multi-centre, randomised, double-blind phase II study comparing cediranib (AZD2171) plus gefitinib (Iressa, ZD1839) with cediranib plus placebo in subjects with recurrent/progressive glioblastoma (DORIC Trial) - Phase II trial of cediranib +/- gefitinib for recurrent glioblastoma
- Conditions
- GlioblastomaMedDRA version: 13.1 Level: PT Classification code 10018336 Term: Glioblastoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
- Registration Number
- EUCTR2010-021531-13-GB
- Lead Sponsor
- Joint UCLH and UCL Biomedical Research Unit
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 38
•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
•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 <1.5g in a 24 hr period or UPC (Urine Protein: Creatinine) ratio <1.5
•History of significant gastrointestinal impairment, as judged by the investigator, that would significantly affect the absorption of cediranib or gefitinib, including the ability to swallow the tablet whole
•Patients with a history of poorly controlled hypertension with resting blood pressure >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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method