Trial Outcomes & Findings for Cediranib Maleate With or Without Gefitinib in Treating Patients With Recurrent or Progressive Glioblastoma (NCT NCT01310855)

Last Updated: 2017-05-31

Results Overview

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. The progression definition will be based on modified RANO criteria (Wen 2010), such that progression will be defined as the earliest time that at least one of the following occurs: 1. Clinical deterioration 2. Failure to return for evaluation as a result of death or deteriorating condition Or, by retrospective radiographic central review: 3. Any new lesion 4. Increase in ≥25% of sum of the products of perpendicular diameters of enhancing lesions compared with baseline scan, on stable or increasing doses of steroids (dexamethasone) compared to baseline (T1 post-contrast scan) 5. Clear progression of non-measureable disease 6. Significant increase in T2/FLAIR non-enhancing lesion - on stable or increasing steroids (dexamethasone) compared with baseline or best response not caused by co-morbid events.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

38 participants

Primary outcome timeframe

from the date of randomisation to the date of first progression or death due to any cause, until 6 months from the date the last patient finished trial treatment (the day after the date that the last trial drug was taken)

Results posted on

2017-05-31

Participant Flow

Trial closed prematurely because cediranib manufacture was discontinued by AZ. Only 38 patients were recruited

Participant milestones

Participant milestones
Measure	Cediranib & Gefitinib Cediranib maleate 30mg od orally and gefitinib 500mg od orally. Each cycle of treatment lasts 6 weeks. Treatment will continue until confirmation of progression, patient decision or the development of unacceptable toxicity (if there is radiological progression only treatment can continue if the investigator has the opinion that the patient is receiving benefit. cediranib maleate gefitinib	Cediranbib & Placebo Cediranib maleate 30mg od orally and placebo 500mg od orally. Each cycle of treatment lasts 6 weeks. Treatment will continue until confirmation of progression, patient decision or the development of unacceptable toxicity (if there is radiological progression only treatment can continue if the investigator has the opinion that the patient is receiving benefit. cediranib maleate Placebo
Overall Study STARTED	19	19
Overall Study COMPLETED	19	19
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Cediranib Maleate With or Without Gefitinib in Treating Patients With Recurrent or Progressive Glioblastoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cediranib & Gefitinib n=19 Participants Cediranib maleate 30mg od orally and gefitinib 500mg od orally. Each cycle of treatment lasts 6 weeks. Treatment will continue until confirmation of progression, patient decision or the development of unacceptable toxicity (if there is radiological progression only treatment can continue if the investigator has the opinion that the patient is receiving benefit. cediranib maleate gefitinib	Cediranbib & Placebo n=19 Participants Cediranib maleate 30mg od orally and placebo 500mg od orally. Each cycle of treatment lasts 6 weeks. Treatment will continue until confirmation of progression, patient decision or the development of unacceptable toxicity (if there is radiological progression only treatment can continue if the investigator has the opinion that the patient is receiving benefit. cediranib maleate Placebo	Total n=38 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Categorical Between 18 and 65 years	15 Participants n=99 Participants	15 Participants n=107 Participants	30 Participants n=206 Participants
Age, Categorical >=65 years	4 Participants n=99 Participants	4 Participants n=107 Participants	8 Participants n=206 Participants
Age, Continuous	54.4 years n=99 Participants	56.9 years n=107 Participants	55.7 years n=206 Participants
Sex: Female, Male Female	13 Participants n=99 Participants	14 Participants n=107 Participants	27 Participants n=206 Participants
Sex: Female, Male Male	6 Participants n=99 Participants	5 Participants n=107 Participants	11 Participants n=206 Participants
Region of Enrollment United Kingdom	19 participants n=99 Participants	19 participants n=107 Participants	38 participants n=206 Participants

PRIMARY outcome

Timeframe: from the date of randomisation to the date of first progression or death due to any cause, until 6 months from the date the last patient finished trial treatment (the day after the date that the last trial drug was taken)

Outcome measures

Outcome measures
Measure	Cediranib & Gefitinib n=19 Participants Cediranib maleate 30mg od orally and gefitinib 500mg od orally. Each cycle of treatment lasts 6 weeks. Treatment will continue until confirmation of progression, patient decision or the development of unacceptable toxicity (if there is radiological progression only treatment can continue if the investigator has the opinion that the patient is receiving benefit. cediranib maleate gefitinib	Cediranbib & Placebo n=19 Participants Cediranib maleate 30mg od orally and placebo 500mg od orally. Each cycle of treatment lasts 6 weeks. Treatment will continue until confirmation of progression, patient decision or the development of unacceptable toxicity (if there is radiological progression only treatment can continue if the investigator has the opinion that the patient is receiving benefit. cediranib maleate Placebo
Progression-free Survival	3.6 months Interval 2.8 to 4.1	2.8 months Interval 2.1 to 3.4

SECONDARY outcome

Timeframe: from date of randomization to date of Death due to any cause.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from baseline scan to six week and 12 week scans

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from the date of randomisation to 6 months

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from randomization to first increase in dexamethasone dose

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from date of randomization to the date of first neurological status worsening in comparison to baseline (first of 2 confirmatory reports at 2 consecutive visits, 6 weeks apart) as assessed by the clinician, or until date of death, whichever is first.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from date of randomisation to death

Outcome measures

Outcome data not reported

Adverse Events

Cediranib & Gefitinib

Serious events: 5 serious events

Other events: 16 other events

Deaths: 0 deaths

Cediranbib & Placebo

Serious events: 7 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cediranib & Gefitinib n=18 participants at risk Cediranib maleate 30mg od orally and gefitinib 500mg od orally. Each cycle of treatment lasts 6 weeks. Treatment will continue until confirmation of progression, patient decision or the development of unacceptable toxicity (if there is radiological progression only treatment can continue if the investigator has the opinion that the patient is receiving benefit. Due to the early discontinuation of Cediranib by AZ, the trial was discontinued early so that only 38 patients (19 per arm) were recruited. One patient in the Cediranib arm did not complete their patient diary, and it was not known how much of the trial treatment they had. Therefore the adverse events reported by the patient could not be attributed to the trial treatment and they were excluded from all analyses.	Cediranbib & Placebo n=19 participants at risk Cediranib maleate 30mg od orally and placebo 500mg od orally. Each cycle of treatment lasts 6 weeks. Treatment will continue until confirmation of progression, patient decision or the development of unacceptable toxicity (if there is radiological progression only treatment can continue if the investigator has the opinion that the patient is receiving benefit. Due to the early discontinuation of Cediranib by AZ, the trial was discontinued early so that only 38 patients (19 per arm) were recruited.
Vascular disorders Pulmonary embolism	5.6% 1/18	0.00% 0/19
Vascular disorders Thromboembolic event	11.1% 2/18	5.3% 1/19
Injury, poisoning and procedural complications Fall	0.00% 0/18	10.5% 2/19
Investigations Alanine aminotransferase increased	0.00% 0/18	5.3% 1/19
Cardiac disorders Sinus tachycardia	0.00% 0/18	5.3% 1/19
Nervous system disorders Ataxia	11.1% 2/18	0.00% 0/19
Nervous system disorders Cognitive disturbance	5.6% 1/18	0.00% 0/19
Nervous system disorders dysphasia	5.6% 1/18	0.00% 0/19
Nervous system disorders headache	5.6% 1/18	0.00% 0/19
Nervous system disorders movement involuntary	5.6% 1/18	0.00% 0/19
Nervous system disorders other, hemispatial neglect of right arm	5.6% 1/18	0.00% 0/19
Nervous system disorders other - right arm numbness	5.6% 1/18	0.00% 0/19
Nervous system disorders other - right homonymous hemiopia	5.6% 1/18	0.00% 0/19
Nervous system disorders other - reduced mobility	5.6% 1/18	0.00% 0/19
Nervous system disorders other - weakness in right arm	5.6% 1/18	0.00% 0/19
Nervous system disorders seizure	11.1% 2/18	0.00% 0/19
Nervous system disorders stroke	5.6% 1/18	0.00% 0/19
Psychiatric disorders confusion	5.6% 1/18	0.00% 0/19
Infections and infestations other	0.00% 0/18	5.3% 1/19
Infections and infestations lung infection	0.00% 0/18	5.3% 1/19
Infections and infestations sepsis	11.1% 2/18	0.00% 0/19
Infections and infestations skin infection	5.6% 1/18	0.00% 0/19
Infections and infestations wound infection	5.6% 1/18	0.00% 0/19
Endocrine disorders cushingoid	0.00% 0/18	5.3% 1/19

Other adverse events

Other adverse events
Measure	Cediranib & Gefitinib n=18 participants at risk Cediranib maleate 30mg od orally and gefitinib 500mg od orally. Each cycle of treatment lasts 6 weeks. Treatment will continue until confirmation of progression, patient decision or the development of unacceptable toxicity (if there is radiological progression only treatment can continue if the investigator has the opinion that the patient is receiving benefit. Due to the early discontinuation of Cediranib by AZ, the trial was discontinued early so that only 38 patients (19 per arm) were recruited. One patient in the Cediranib arm did not complete their patient diary, and it was not known how much of the trial treatment they had. Therefore the adverse events reported by the patient could not be attributed to the trial treatment and they were excluded from all analyses.	Cediranbib & Placebo n=19 participants at risk Cediranib maleate 30mg od orally and placebo 500mg od orally. Each cycle of treatment lasts 6 weeks. Treatment will continue until confirmation of progression, patient decision or the development of unacceptable toxicity (if there is radiological progression only treatment can continue if the investigator has the opinion that the patient is receiving benefit. Due to the early discontinuation of Cediranib by AZ, the trial was discontinued early so that only 38 patients (19 per arm) were recruited.
Vascular disorders hypertension	27.8% 5/18	5.3% 1/19
Vascular disorders thromboembolic event	5.6% 1/18	5.3% 1/19
General disorders fatigue	22.2% 4/18	31.6% 6/19
Psychiatric disorders cognitive disburbance	11.1% 2/18	0.00% 0/19
Psychiatric disorders confusion	5.6% 1/18	0.00% 0/19
Injury, poisoning and procedural complications fall	0.00% 0/18	10.5% 2/19
Investigations lymphopenia	16.7% 3/18	10.5% 2/19
Investigations alanine aminotransferase increased	0.00% 0/18	10.5% 2/19
Investigations cholesterol high	0.00% 0/18	5.3% 1/19
Investigations hypertrigylceridomia	0.00% 0/18	5.3% 1/19
Investigations GGT increased	0.00% 0/18	5.3% 1/19
Blood and lymphatic system disorders haemorrage	0.00% 0/18	5.3% 1/19
Nervous system disorders dysphasia	5.6% 1/18	10.5% 2/19
Nervous system disorders headache	11.1% 2/18	5.3% 1/19
Nervous system disorders pain	5.6% 1/18	5.3% 1/19
Nervous system disorders seizure	5.6% 1/18	0.00% 0/19
Nervous system disorders other	5.6% 1/18	0.00% 0/19
Nervous system disorders movements involuntary	5.6% 1/18	0.00% 0/19
Nervous system disorders paresthesia	5.6% 1/18	0.00% 0/19
Eye disorders eye disorder	11.1% 2/18	0.00% 0/19
Eye disorders blurred vision	5.6% 1/18	0.00% 0/19
Gastrointestinal disorders diarrhoea	5.6% 1/18	0.00% 0/19
Gastrointestinal disorders mucositis oral	5.6% 1/18	0.00% 0/19
Gastrointestinal disorders stomatitis	0.00% 0/18	5.3% 1/19
Skin and subcutaneous tissue disorders skin ulceration	5.6% 1/18	0.00% 0/19
Musculoskeletal and connective tissue disorders muscle weakness right handed	5.6% 1/18	0.00% 0/19
Musculoskeletal and connective tissue disorders generalised muscle weakness	5.6% 1/18	0.00% 0/19
Musculoskeletal and connective tissue disorders musculoskeletal and connective tissue disorder	5.6% 1/18	0.00% 0/19
Endocrine disorders cushingoid	0.00% 0/18	5.3% 1/19
Metabolism and nutrition disorders anorexia	5.6% 1/18	15.8% 3/19
Metabolism and nutrition disorders hyperglycemia	5.6% 1/18	5.3% 1/19
Infections and infestations rash pustular	11.1% 2/18	5.3% 1/19
Infections and infestations sepsis	11.1% 2/18	0.00% 0/19
Infections and infestations infection	5.6% 1/18	0.00% 0/19
Investigations aspartate aminotransferase increased	0.00% 0/18	5.3% 1/19

Additional Information

Mark Phillips

UCL and CTC Cancer Trials Centre

Phone: 0207 679 9139

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The excerpts below are present on all site agreements between site staff (including PI) and the sponsor: * The Site shall ensure that only those of its employees or officers directly concerned with the conduct of the Trial at the Site shall have access to the Confidential Information relating to the Trial. * The Site agrees it will not publish any information, data or results without the express written permission of the TMG, such permission not to be unreasonably withheld.
Publication restrictions are in place

Restriction type: OTHER