Cediranib maleate with or without gefitinib in treating patients with recurrent or progressive glioblastoma
- Conditions
- Brain TumourCancerMalignant neoplasm of brain
- Registration Number
- ISRCTN00549973
- Lead Sponsor
- niversity College London (UK)
- Brief Summary
2016 Results article in https://www.ncbi.nlm.nih.gov/pubmed/27232884 results
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 38
1. Provision of informed consent
2. Age =18 years
3. Life expectancy = 12 weeks
4. Histological/cytological confirmation of glioblastoma (WHO grade IV)
5. 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.)
6. Patients must have been on no steroids or a stable dose of steroids (dexamethasone) for at least 5 days before the baseline MRI
7. 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
7.1. It is not essential that the entire Stupp regimen of 6 cycles of adjuvant temozolomide following chemoradiotherapy has been completed
7.2. The last dose of temozolomide must be more than 28 days from enrolment
7.3. Gliadel® wafers are permitted, as it is part of local treatment
7.4. No other previous treatment for glioblastoma is permitted (other than steroids)
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.
11. For inclusion in the genetic research, patients must fulfil the following criterion:
11.1. Provision of informed consent for genetic research (separate consent required for tumour biopsy, blood sample, and post mortem donations)
11.2. If a patient declines to participate in any of the genetic research, there will be no penalty or loss of benefit to the patient
11.3. The patient will not be excluded from other aspects of the study described in this Clinical Study Protocol, so long as they consent to the main study
1. 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
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 =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 <1.5g in a 24 hr period or UPC (Urine Protein: Creatinine) ratio <1.5
7. 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
8. 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
9. Any evidence of severe or uncontrolled diseases (e.g. unstable or uncompensated respiratory, cardiac, hepatic or renal disease)
10. Unresolved toxicity >CTC AE 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. Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy
13. Significant haemorrhage (>30mL bleeding/episode in previous 3 months) or haemoptysis (>5mL fresh blood in previous 4 weeks)
14. Recent (<14 days) major surgery or brain biopsy
15. Recent craniotomy (<28 days) prior to first dose, or a surgical incision that is not fully healed
16. Pregnant or breast-feeding women or women of childbearing potential with a positive pregnancy test prior to receiving study medication
17. Known hypersensitivity to cediranib, gefitinib or any of its excipients
18. 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
19. Known infection with hepatitis B or C or HIV
20. Involvement in the planning and conduct of the study (applies to both UCL CTC, AstraZeneca staff and staff at the study site)
21. 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
22. Previous enrolment as part of the present study
23. Treatment with an investigational drug within 30 days prior to the first dose of cediranib/gefitinib
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method