Cediranib in Combination with Lomustine Chemotherapy in Recurrent Glioblastoma - REGAL

Study identifier:D8480C00055

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Phase III, Randomised, Parallel Group, Multi-Centre Study in Recurrent Glioblastoma Patients to Compare the Efficacy of Cediranib [RECENTIN™, AZD2171] Monotherapy and the Combination of Cediranib with Lomustine to the Efficacy of Lomustine Alone

Medical condition

Recurrent Glioblastoma

Phase

Phase 3

Healthy volunteers

Study drug

Cediranib, Lomustine Chemotherapy, Placebo Cediranib

Sex

All

Actual Enrollment

423

Study type

Interventional

Age

18 Years - 100 Years

Date

Study Start Date: 01 Oct 2008

Primary Completion Date: 01 Apr 2010

Study Completion Date: 01 Sept 2016

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Oct 2016 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Location

Research Site

Graz, Austria

Location

Research Site

Woodville, Australia

Location

Research Site

Nedlands, Australia

Location

Research Site

Camperdown, Australia

Location

Research Site

Parkville, Australia

Location

Research Site

Heidelberg, Australia

Location

Research Site

St Leonards, Australia

Location

Research Site

Brussels (Woluwé-St-Lambert), Belgium

Arms	Assigned Interventions
Experimental: Cediranib 30mg Cediranib 30mg	Drug: Cediranib 30 mg/day, oral, until progression
Other: Cediranib 20mg + lomustine Cediranib 20mg + lomustine	Drug: Cediranib 20 mg/day, oral, until progression Drug: Lomustine Chemotherapy 110 mg/m2 / Q6W, oral, until progression
Active Comparator: Lomustine and Placebo Cediranib Lomustine and Placebo Cediranib	Drug: Lomustine Chemotherapy 110 mg/m2 / Q6W, oral, until progression Drug: Placebo Cediranib Oral, until progression

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
423 patients were enrolled in to the study but did not start the study. They did not go on to be randomized.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Randomised=Full Analysis Set (ITT): Cediranib 30 mg=131, Cediranib 20 mg + Lomustine=129, Placebo + Lomustine=65; ITT with measurable disease at baseline (based on site review): Cediranib 30 mg=115, Cediranib 20 mg + Lomustine=112, Placebo + Lomustine=55; Safety Set: Cediranib 30 mg=128, Cediranib 20 mg + Lomustine=123, Placebo + Lomustine=64

Reporting Groups

	Description
Cediranib 30mg	Cediranib 30mg/Day
Cediranib 20mg + Lomustine 110mg	Cediranib 20mg/Day + Lomustine 110mg/m2/Day
Lomustine 110mg	Lomustine 110mg/m2/Day + Placebo cediranib

Participant Flow: Overall Study

	Cediranib 30mg	Cediranib 20mg + Lomustine 110mg	Lomustine 110mg
STARTED	131	129	65
COMPLETED	41	46	28
NOT COMPLETED	90	83	37
Lost to Follow-up	1	1	0
Death	85	73	33
Withdrawal by Subject	3	4	3
Incorrect enrol/elig crit not fulfilled	1	5	1

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
Cediranib 30mg	Cediranib 30mg/Day
Cediranib 20mg + Lomustine 110mg	Cediranib 20mg/Day + Lomustine 110mg/m2/Day
Lomustine 110mg	Lomustine 110mg/m2/Day + Placebo cediranib

Baseline Measures

	Cediranib 30mg	Cediranib 20mg + Lomustine 110mg	Lomustine 110mg	Total
Number of Participants [units: Participants]	131	129	65	325
Age Continuous ^[1] [units: years] Mean ± Standard Deviation
Gender, Male/Female ^[2] [units: ]
Female	46	44	24	114
Male	85	85	41	211

Outcome Measures

1. Primary Outcome Measure: Progression free survival (PFS) [ Time Frame: Baseline at 6 weeks and then every 6 weeks to discontinuation ]

Measure Type	Primary
Measure Name	Progression free survival (PFS)
Measure Description	For patients with measurable disease at entry (at least one lesion that has a shortest diameter ≥10 mm at baseline on 2 axial slices), PFS will be defined as the earliest time that: 1. The sum of the products of the largest perpendicular diameters of contrast enhancement for all lesions has increased by a greater than or equal to 25% in comparison to the nadir scan as long as the shortest diameter is ≥15 mm. If the dose of steroids has been reduced within the 10 days prior to the scan being conducted, progression will be based on a follow-up scan performed after the dose of steroids has been stabilized for 10 days. 2. The patient has died from any cause. 3. A new lesion is detected that is outside the original tumor volume and has a shortest diameter ≥10 mm.
Time Frame	Baseline at 6 weeks and then every 6 weeks to discontinuation
Safety Issue?

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No text entered.

2. Secondary Outcome Measure: Overall survival (OS) [ Time Frame: Baseline through to date of death up to 25th April 2010 ]

Measure Type	Secondary
Measure Name	Overall survival (OS)
Measure Description	Number of months from randomisation to the date of death from any cause
Time Frame	Baseline through to date of death up to 25th April 2010
Safety Issue?

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No text entered.

3. Secondary Outcome Measure: Response rate [ Time Frame: Baseline at 6 weeks and then every 6 weeks to discontinuation ]

Measure Type	Secondary
Measure Name	Response rate
Measure Description	An individual visit response of PR was defined as a greater than or equal to 50% reduction in the sum of the products of the largest perpendicular diameters of contrast enhancement for all lesions compared to baseline as long as the steroid dose has not been increased within the previous 10 days and no new lesions are present. An individual visit response of CR was defined as the complete disappearance of all tumor on MRI scan.
Time Frame	Baseline at 6 weeks and then every 6 weeks to discontinuation
Safety Issue?

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No text entered.

4. Secondary Outcome Measure: Alive and progression free rate at 6 months (APF6) [ Time Frame: 6 Months ]

Measure Type	Secondary
Measure Name	Alive and progression free rate at 6 months (APF6)
Measure Description	Proportion of patients alive and progression free at 6 months (based on central review) as estimated from Kaplan-Meier techniques. Values are percentages.
Time Frame	6 Months
Safety Issue?

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No text entered.

5. Secondary Outcome Measure: Daily steroid dose [ Time Frame: Baseline to the date of first documented progression or date of death or study discontinuation, whichever came first, assed up to 2014-April-25 ]

Measure Type	Secondary
Measure Name	Daily steroid dose
Measure Description	The mean steroid dosage prior to treatment will be considered as the patient’s baseline. The percent change in average daily steroid dosage from baseline is calculated by following formula: PC = (md – bm)/bm*100; where PC is the percent change in average daily steroid dosage from baseline; md the mean daily steroid dosage recorded from the first day of therapy to progression; and bm the baseline mean.
Time Frame	Baseline to the date of first documented progression or date of death or study discontinuation, whichever came first, assed up to 2014-April-25
Safety Issue?

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No text entered.

6. Secondary Outcome Measure: Steroid free days [ Time Frame: Baseline to the date of first documented progression or date of death or study discontinuation, whichever came first, assessed up to 2014-April-25 ]

Measure Type	Secondary
Measure Name	Steroid free days
Measure Description	Number of days known not to have used any steroids prior to progression
Time Frame	Baseline to the date of first documented progression or date of death or study discontinuation, whichever came first, assessed up to 2014-April-25
Safety Issue?

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No text entered.

Serious Adverse Events

Time Frame	No text entered.
Additional Description	Adverse events are assessed on all patients who meet the Safety set criteria i.e. all patients who were randomized and received at least one dose of study drug. Safety Set: Cediranib 30 mg=128, Cediranib 20 mg + Lomustine=123, Placebo + Lomustine=64

Reporting Groups

	Description
Cediranib 30mg	Cediranib 30mg/Day
Cediranib 20mg + Lomustine 110mg	Cediranib 20mg/Day + Lomustine 110mg/m2/Day
Lomustine 110mg	Lomustine 110mg/m2/Day + Placebo cediranib

Serious Adverse Events

Cediranib 30mg

Cediranib 20mg + Lomustine 110mg

Lomustine 110mg

Total, serious adverse events

# participants affected / at risk

55/128 (42.97%)

45/123 (36.59%)

26/64 (40.63%)

Blood and lymphatic system disorders

Thrombocytopenia¹,^†

# participants affected / at risk

1/128 (0.78%)

8/123 (6.50%)

2/64 (3.13%)

Blood and lymphatic system disorders

Neutropenia¹,^†

# participants affected / at risk

0/128 (0.00%)

5/123 (4.07%)

0/64 (0.00%)

Blood and lymphatic system disorders

Anaemia¹,^†

# participants affected / at risk

0/128 (0.00%)

3/123 (2.44%)

0/64 (0.00%)

Blood and lymphatic system disorders

Febrile Neutropenia¹,^†

# participants affected / at risk

0/128 (0.00%)

2/123 (1.63%)

0/64 (0.00%)

Blood and lymphatic system disorders

Pancytopenia¹,^†

# participants affected / at risk

0/128 (0.00%)

1/123 (0.81%)

0/64 (0.00%)

Cardiac disorders

Acute Myocardial Infarction¹,^†

# participants affected / at risk

0/128 (0.00%)

1/123 (0.81%)

0/64 (0.00%)

Cardiac disorders

Angina Unstable¹,^†

# participants affected / at risk

0/128 (0.00%)

1/123 (0.81%)

0/64 (0.00%)

Cardiac disorders

Tachycardia¹,^†

# participants affected / at risk

1/128 (0.78%)

0/123 (0.00%)

0/64 (0.00%)

Endocrine disorders

Addison's Disease¹,^†

# participants affected / at risk

0/128 (0.00%)

1/123 (0.81%)

0/64 (0.00%)

Endocrine disorders

Hypothyroidism¹,^†

# participants affected / at risk

1/128 (0.78%)

0/123 (0.00%)

0/64 (0.00%)

Gastrointestinal disorders

Abdominal Pain¹,^†

# participants affected / at risk

2/128 (1.56%)

1/123 (0.81%)

0/64 (0.00%)

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

2/128 (1.56%)

2/123 (1.63%)

1/64 (1.56%)

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

0/128 (0.00%)

2/123 (1.63%)

0/64 (0.00%)

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

0/128 (0.00%)

2/123 (1.63%)

0/64 (0.00%)

Gastrointestinal disorders

Abdominal Pain Upper¹,^†

# participants affected / at risk

0/128 (0.00%)

1/123 (0.81%)

0/64 (0.00%)

Gastrointestinal disorders

Dysphagia¹,^†

# participants affected / at risk

1/128 (0.78%)

0/123 (0.00%)

0/64 (0.00%)

Gastrointestinal disorders

Rectal Haemorrhage¹,^†

# participants affected / at risk

1/128 (0.78%)

0/123 (0.00%)

0/64 (0.00%)

Gastrointestinal disorders

Rectal Perforation¹,^†

# participants affected / at risk

1/128 (0.78%)

0/123 (0.00%)

0/64 (0.00%)

General disorders

General Physical Health Deterioration¹,^†

# participants affected / at risk

2/128 (1.56%)

0/123 (0.00%)

0/64 (0.00%)

General disorders

Death¹,^†

# participants affected / at risk

0/128 (0.00%)

1/123 (0.81%)

0/64 (0.00%)

General disorders

Fatigue¹,^†

# participants affected / at risk

1/128 (0.78%)

1/123 (0.81%)

0/64 (0.00%)

General disorders

Gait Disturbance¹,^†

# participants affected / at risk

0/128 (0.00%)

1/123 (0.81%)

0/64 (0.00%)

General disorders

Pyrexia¹,^†

# participants affected / at risk

0/128 (0.00%)

1/123 (0.81%)

1/64 (1.56%)

Hepatobiliary disorders

Cholecystitis¹,^†

# participants affected / at risk

0/128 (0.00%)

1/123 (0.81%)

0/64 (0.00%)

Hepatobiliary disorders

Hepatic Steatosis¹,^†

# participants affected / at risk

0/128 (0.00%)

1/123 (0.81%)

0/64 (0.00%)

Immune system disorders

Hypersensitivity¹,^†

# participants affected / at risk

0/128 (0.00%)

1/123 (0.81%)

0/64 (0.00%)

Infections and infestations

Pneumonia¹,^†

# participants affected / at risk

4/128 (3.13%)

3/123 (2.44%)

0/64 (0.00%)

Infections and infestations

Bronchitis¹,^†

# participants affected / at risk

0/128 (0.00%)

2/123 (1.63%)

0/64 (0.00%)

Infections and infestations

Bronchopneumonia¹,^†

# participants affected / at risk

1/128 (0.78%)

1/123 (0.81%)

0/64 (0.00%)

Infections and infestations

Cellulitis¹,^†

# participants affected / at risk

1/128 (0.78%)

0/123 (0.00%)

0/64 (0.00%)

Infections and infestations

Herpes Zoster¹,^†

# participants affected / at risk

0/128 (0.00%)

1/123 (0.81%)

0/64 (0.00%)

Infections and infestations

Herpes Zoster Ophthalmic¹,^†

# participants affected / at risk

1/128 (0.78%)

0/123 (0.00%)

0/64 (0.00%)

Infections and infestations

Influenza¹,^†

# participants affected / at risk

0/128 (0.00%)

1/123 (0.81%)

0/64 (0.00%)

Infections and infestations

Rectal Abscess¹,^†

# participants affected / at risk

1/128 (0.78%)

0/123 (0.00%)

0/64 (0.00%)

Infections and infestations

Sepsis¹,^†

# participants affected / at risk

0/128 (0.00%)

0/123 (0.00%)

1/64 (1.56%)

Infections and infestations

Wound Infection¹,^†

# participants affected / at risk

1/128 (0.78%)

0/123 (0.00%)

0/64 (0.00%)

Injury, poisoning and procedural complications

Concussion¹,^†

# participants affected / at risk

0/128 (0.00%)

1/123 (0.81%)

0/64 (0.00%)

Injury, poisoning and procedural complications

Feeding Tube Complication¹,^†

# participants affected / at risk

1/128 (0.78%)

0/123 (0.00%)

0/64 (0.00%)

Injury, poisoning and procedural complications

Head Injury¹,^†

# participants affected / at risk

0/128 (0.00%)

0/123 (0.00%)

1/64 (1.56%)

Injury, poisoning and procedural complications

Joint Dislocation¹,^†

# participants affected / at risk

1/128 (0.78%)

0/123 (0.00%)

0/64 (0.00%)

Injury, poisoning and procedural complications

Subdural Haematoma¹,^†

# participants affected / at risk

1/128 (0.78%)

0/123 (0.00%)

0/64 (0.00%)

Investigations

Alanine Aminotransferase Increased¹,^†

# participants affected / at risk

1/128 (0.78%)

0/123 (0.00%)

0/64 (0.00%)

Metabolism and nutrition disorders

Hyperglycaemia¹,^†

# participants affected / at risk

0/128 (0.00%)

0/123 (0.00%)

2/64 (3.13%)

Metabolism and nutrition disorders

Dehydration¹,^†

# participants affected / at risk

0/128 (0.00%)

1/123 (0.81%)

0/64 (0.00%)

Metabolism and nutrition disorders

Hypokalaemia¹,^†

# participants affected / at risk

1/128 (0.78%)

1/123 (0.81%)

0/64 (0.00%)

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

1/128 (0.78%)

0/123 (0.00%)

0/64 (0.00%)

Musculoskeletal and connective tissue disorders

Back Pain¹,^†

# participants affected / at risk

1/128 (0.78%)

1/123 (0.81%)

1/64 (1.56%)

Musculoskeletal and connective tissue disorders

Mobility Decreased¹,^†

# participants affected / at risk

1/128 (0.78%)

0/123 (0.00%)

0/64 (0.00%)

Musculoskeletal and connective tissue disorders

Muscle Haemorrhage¹,^†

# participants affected / at risk

1/128 (0.78%)

0/123 (0.00%)

0/64 (0.00%)

Musculoskeletal and connective tissue disorders

Muscular Weakness¹,^†

# participants affected / at risk

1/128 (0.78%)

1/123 (0.81%)

0/64 (0.00%)

Musculoskeletal and connective tissue disorders

Osteoporosis¹,^†

# participants affected / at risk

0/128 (0.00%)

0/123 (0.00%)

1/64 (1.56%)

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Tumour Haemorrhage¹,^†

# participants affected / at risk

0/128 (0.00%)

1/123 (0.81%)

0/64 (0.00%)

Nervous system disorders

Convulsion¹,^†

# participants affected / at risk

11/128 (8.59%)

3/123 (2.44%)

2/64 (3.13%)

Nervous system disorders

Grand Mal Convulsion¹,^†

# participants affected / at risk

3/128 (2.34%)

1/123 (0.81%)

0/64 (0.00%)

Nervous system disorders

Hemiparesis¹,^†

# participants affected / at risk

3/128 (2.34%)

0/123 (0.00%)

1/64 (1.56%)

Nervous system disorders

Cerebral Haemorrhage¹,^†

# participants affected / at risk

0/128 (0.00%)

0/123 (0.00%)

2/64 (3.13%)

Nervous system disorders

Headache¹,^†

# participants affected / at risk

2/128 (1.56%)

1/123 (0.81%)

1/64 (1.56%)

Nervous system disorders

Hydrocephalus¹,^†

# participants affected / at risk

0/128 (0.00%)

2/123 (1.63%)

0/64 (0.00%)

Nervous system disorders

Ischaemic Stroke¹,^†

# participants affected / at risk

2/128 (1.56%)

0/123 (0.00%)

0/64 (0.00%)

Nervous system disorders

Neurological Symptom¹,^†

# participants affected / at risk

0/128 (0.00%)

0/123 (0.00%)

2/64 (3.13%)

Nervous system disorders

Partial Seizures¹,^†

# participants affected / at risk

1/128 (0.78%)

0/123 (0.00%)

2/64 (3.13%)

Nervous system disorders

Aphasia¹,^†

# participants affected / at risk

0/128 (0.00%)

1/123 (0.81%)

0/64 (0.00%)

Nervous system disorders

Ataxia¹,^†

# participants affected / at risk

1/128 (0.78%)

0/123 (0.00%)

0/64 (0.00%)

Nervous system disorders

Cerebral Cyst¹,^†

# participants affected / at risk

0/128 (0.00%)

0/123 (0.00%)

1/64 (1.56%)

Nervous system disorders

Cerebral Haematoma¹,^†

# participants affected / at risk

0/128 (0.00%)

0/123 (0.00%)

1/64 (1.56%)

Nervous system disorders

Cerebral Venous Thrombosis¹,^†

# participants affected / at risk

0/128 (0.00%)

1/123 (0.81%)

0/64 (0.00%)

Nervous system disorders

Complex Partial Seizures¹,^†

# participants affected / at risk

1/128 (0.78%)

1/123 (0.81%)

0/64 (0.00%)

Nervous system disorders

Encephalopathy¹,^†

# participants affected / at risk

0/128 (0.00%)

1/123 (0.81%)

0/64 (0.00%)

Nervous system disorders

Intracranial Pressure Increased¹,^†

# participants affected / at risk

0/128 (0.00%)

0/123 (0.00%)

1/64 (1.56%)

Nervous system disorders

Ischaemic Cerebral Infarction¹,^†

# participants affected / at risk

0/128 (0.00%)

1/123 (0.81%)

0/64 (0.00%)

Nervous system disorders

Neurological Decompensation¹,^†

# participants affected / at risk

1/128 (0.78%)

1/123 (0.81%)

0/64 (0.00%)

Nervous system disorders

Peripheral Motor Neuropathy¹,^†

# participants affected / at risk

0/128 (0.00%)

1/123 (0.81%)

0/64 (0.00%)

Nervous system disorders

Sinus Headache¹,^†

# participants affected / at risk

0/128 (0.00%)

0/123 (0.00%)

1/64 (1.56%)

Nervous system disorders

Somnolence¹,^†

# participants affected / at risk

1/128 (0.78%)

0/123 (0.00%)

0/64 (0.00%)

Nervous system disorders

Speech Disorder¹,^†

# participants affected / at risk

1/128 (0.78%)

0/123 (0.00%)

0/64 (0.00%)

Nervous system disorders

Syncope¹,^†

# participants affected / at risk

0/128 (0.00%)

0/123 (0.00%)

1/64 (1.56%)

Psychiatric disorders

Confusional State¹,^†

# participants affected / at risk

1/128 (0.78%)

2/123 (1.63%)

0/64 (0.00%)

Psychiatric disorders

Mental Status Changes¹,^†

# participants affected / at risk

2/128 (1.56%)

0/123 (0.00%)

1/64 (1.56%)

Psychiatric disorders

Aggression¹,^†

# participants affected / at risk

1/128 (0.78%)

0/123 (0.00%)

0/64 (0.00%)

Psychiatric disorders

Anxiety¹,^†

# participants affected / at risk

1/128 (0.78%)

0/123 (0.00%)

0/64 (0.00%)

Psychiatric disorders

Personality Change¹,^†

# participants affected / at risk

1/128 (0.78%)

0/123 (0.00%)

0/64 (0.00%)

Psychiatric disorders

Suicide Attempt¹,^†

# participants affected / at risk

0/128 (0.00%)

0/123 (0.00%)

1/64 (1.56%)

Reproductive system and breast disorders

Menorrhagia¹,^†

# participants affected / at risk

0/128 (0.00%)

1/123 (0.81%)

0/64 (0.00%)

Respiratory, thoracic and mediastinal disorders

Pulmonary Embolism¹,^†

# participants affected / at risk

4/128 (3.13%)

6/123 (4.88%)

3/64 (4.69%)

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

1/128 (0.78%)

0/123 (0.00%)

0/64 (0.00%)

Respiratory, thoracic and mediastinal disorders

Dyspnoea Exertional¹,^†

# participants affected / at risk

0/128 (0.00%)

0/123 (0.00%)

1/64 (1.56%)

Respiratory, thoracic and mediastinal disorders

Pneumothorax¹,^†

# participants affected / at risk

1/128 (0.78%)

0/123 (0.00%)

0/64 (0.00%)

Skin and subcutaneous tissue disorders

Rash¹,^†

# participants affected / at risk

0/128 (0.00%)

1/123 (0.81%)

0/64 (0.00%)

Skin and subcutaneous tissue disorders

Skin Disorder¹,^†

# participants affected / at risk

1/128 (0.78%)

0/123 (0.00%)

0/64 (0.00%)

Vascular disorders

Deep Vein Thrombosis¹,^†

# participants affected / at risk

2/128 (1.56%)

4/123 (3.25%)

1/64 (1.56%)

Vascular disorders

Hypertension¹,^†

# participants affected / at risk

3/128 (2.34%)

1/123 (0.81%)

0/64 (0.00%)

Vascular disorders

Haematoma¹,^†

# participants affected / at risk

1/128 (0.78%)

0/123 (0.00%)

0/64 (0.00%)

Vascular disorders

Phlebitis¹,^†

# participants affected / at risk

1/128 (0.78%)

0/123 (0.00%)

0/64 (0.00%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 13.0
2	Term from vocabulary,

Other Adverse Events

Time Frame	No text entered.
Additional Description	Adverse events are assessed on all patients who meet the Safety set criteria i.e. all patients who were randomized and received at least one dose of study drug. Safety Set: Cediranib 30 mg=128, Cediranib 20 mg + Lomustine=123, Placebo + Lomustine=64

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Cediranib 30mg	Cediranib 30mg/Day
Cediranib 20mg + Lomustine 110mg	Cediranib 20mg/Day + Lomustine 110mg/m2/Day
Lomustine 110mg	Lomustine 110mg/m2/Day + Placebo cediranib

Other Adverse Events

Cediranib 30mg

Cediranib 20mg + Lomustine 110mg

Lomustine 110mg

Total, other (not including serious) adverse events

# participants affected / at risk

124/128 (96.88%)

120/123 (97.56%)

61/64 (95.31%)

Blood and lymphatic system disorders

Thrombocytopenia¹,^†

# participants affected / at risk

6/128 (4.69%)

69/123 (56.10%)

28/64 (43.75%)

Blood and lymphatic system disorders

Neutropenia¹,^†

# participants affected / at risk

2/128 (1.56%)

28/123 (22.76%)

8/64 (12.50%)

Blood and lymphatic system disorders

Leukopenia¹,^†

# participants affected / at risk

2/128 (1.56%)

25/123 (20.33%)

11/64 (17.19%)

Blood and lymphatic system disorders

Anaemia¹,^†

# participants affected / at risk

1/128 (0.78%)

10/123 (8.13%)

1/64 (1.56%)

Blood and lymphatic system disorders

Lymphopenia¹,^†

# participants affected / at risk

6/128 (4.69%)

8/123 (6.50%)

8/64 (12.50%)

Endocrine disorders

Hypothyroidism¹,^†

# participants affected / at risk

24/128 (18.75%)

10/123 (8.13%)

0/64 (0.00%)

Eye disorders

Vision Blurred¹,^†

# participants affected / at risk

5/128 (3.91%)

6/123 (4.88%)

4/64 (6.25%)

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

91/128 (71.09%)

87/123 (70.73%)

11/64 (17.19%)

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

26/128 (20.31%)

36/123 (29.27%)

22/64 (34.38%)

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

26/128 (20.31%)

26/123 (21.14%)

16/64 (25.00%)

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

10/128 (7.81%)

25/123 (20.33%)

7/64 (10.94%)

Gastrointestinal disorders

Stomatitis¹,^†

# participants affected / at risk

14/128 (10.94%)

3/123 (2.44%)

2/64 (3.13%)

Gastrointestinal disorders

Abdominal Pain¹,^†

# participants affected / at risk

7/128 (5.47%)

11/123 (8.94%)

2/64 (3.13%)

Gastrointestinal disorders

Oral Pain¹,^†

# participants affected / at risk

8/128 (6.25%)

5/123 (4.07%)

4/64 (6.25%)

Gastrointestinal disorders

Abdominal Pain Upper¹,^†

# participants affected / at risk

5/128 (3.91%)

7/123 (5.69%)

4/64 (6.25%)

Gastrointestinal disorders

Dry Mouth¹,^†

# participants affected / at risk

5/128 (3.91%)

7/123 (5.69%)

1/64 (1.56%)

Gastrointestinal disorders

Faecal Incontinence¹,^†

# participants affected / at risk

7/128 (5.47%)

0/123 (0.00%)

0/64 (0.00%)

General disorders

Fatigue¹,^†

# participants affected / at risk

65/128 (50.78%)

72/123 (58.54%)

30/64 (46.88%)

General disorders

Oedema Peripheral¹,^†

# participants affected / at risk

17/128 (13.28%)

16/123 (13.01%)

8/64 (12.50%)

General disorders

Asthenia¹,^†

# participants affected / at risk

5/128 (3.91%)

12/123 (9.76%)

5/64 (7.81%)

Infections and infestations

Upper Respiratory Tract Infection¹,^†

# participants affected / at risk

6/128 (4.69%)

9/123 (7.32%)

3/64 (4.69%)

Infections and infestations

Urinary Tract Infection¹,^†

# participants affected / at risk

5/128 (3.91%)

8/123 (6.50%)

2/64 (3.13%)

Injury, poisoning and procedural complications

Contusion¹,^†

# participants affected / at risk

7/128 (5.47%)

10/123 (8.13%)

2/64 (3.13%)

Injury, poisoning and procedural complications

Fall¹,^†

# participants affected / at risk

5/128 (3.91%)

6/123 (4.88%)

5/64 (7.81%)

Investigations

Platelet Count Decreased¹,^†

# participants affected / at risk

3/128 (2.34%)

21/123 (17.07%)

9/64 (14.06%)

Investigations

White Blood Cell Count Decreased¹,^†

# participants affected / at risk

0/128 (0.00%)

15/123 (12.20%)

7/64 (10.94%)

Investigations

Weight Decreased¹,^†

# participants affected / at risk

6/128 (4.69%)

14/123 (11.38%)

0/64 (0.00%)

Investigations

Alanine Aminotransferase Increased¹,^†

# participants affected / at risk

4/128 (3.13%)

13/123 (10.57%)

2/64 (3.13%)

Investigations

Gamma-Glutamyltransferase Increased¹,^†

# participants affected / at risk

2/128 (1.56%)

13/123 (10.57%)

2/64 (3.13%)

Investigations

Aspartate Aminotransferase Increased¹,^†

# participants affected / at risk

2/128 (1.56%)

9/123 (7.32%)

1/64 (1.56%)

Metabolism and nutrition disorders

Decreased Appetite¹,^†

# participants affected / at risk

16/128 (12.50%)

28/123 (22.76%)

4/64 (6.25%)

Musculoskeletal and connective tissue disorders

Pain In Extremity¹,^†

# participants affected / at risk

4/128 (3.13%)

12/123 (9.76%)

4/64 (6.25%)

Musculoskeletal and connective tissue disorders

Back Pain¹,^†

# participants affected / at risk

7/128 (5.47%)

10/123 (8.13%)

7/64 (10.94%)

Musculoskeletal and connective tissue disorders

Muscular Weakness¹,^†

# participants affected / at risk

10/128 (7.81%)

8/123 (6.50%)

6/64 (9.38%)

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

8/128 (6.25%)

8/123 (6.50%)

1/64 (1.56%)

Musculoskeletal and connective tissue disorders

Muscle Spasms¹,^†

# participants affected / at risk

2/128 (1.56%)

7/123 (5.69%)

3/64 (4.69%)

Nervous system disorders

Headache¹,^†

# participants affected / at risk

35/128 (27.34%)

40/123 (32.52%)

24/64 (37.50%)

Nervous system disorders

Convulsion¹,^†

# participants affected / at risk

17/128 (13.28%)

9/123 (7.32%)

7/64 (10.94%)

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

13/128 (10.16%)

7/123 (5.69%)

4/64 (6.25%)

Nervous system disorders

Aphasia¹,^†

# participants affected / at risk

12/128 (9.38%)

4/123 (3.25%)

3/64 (4.69%)

Nervous system disorders

Lethargy¹,^†

# participants affected / at risk

5/128 (3.91%)

7/123 (5.69%)

3/64 (4.69%)

Nervous system disorders

Hemiparesis¹,^†

# participants affected / at risk

4/128 (3.13%)

4/123 (3.25%)

5/64 (7.81%)

Psychiatric disorders

Confusional State¹,^†

# participants affected / at risk

10/128 (7.81%)

6/123 (4.88%)

1/64 (1.56%)

Psychiatric disorders

Depression¹,^†

# participants affected / at risk

7/128 (5.47%)

10/123 (8.13%)

3/64 (4.69%)

Psychiatric disorders

Anxiety¹,^†

# participants affected / at risk

5/128 (3.91%)

9/123 (7.32%)

3/64 (4.69%)

Psychiatric disorders

Insomnia¹,^†

# participants affected / at risk

9/128 (7.03%)

9/123 (7.32%)

8/64 (12.50%)

Psychiatric disorders

Agitation¹,^†

# participants affected / at risk

8/128 (6.25%)

1/123 (0.81%)

2/64 (3.13%)

Renal and urinary disorders

Urinary Incontinence¹,^†

# participants affected / at risk

10/128 (7.81%)

4/123 (3.25%)

1/64 (1.56%)

Renal and urinary disorders

Polyuria¹,^†

# participants affected / at risk

1/128 (0.78%)

0/123 (0.00%)

4/64 (6.25%)

Respiratory, thoracic and mediastinal disorders

Dysphonia¹,^†

# participants affected / at risk

39/128 (30.47%)

36/123 (29.27%)

6/64 (9.38%)

Respiratory, thoracic and mediastinal disorders

Cough¹,^†

# participants affected / at risk

13/128 (10.16%)

16/123 (13.01%)

5/64 (7.81%)

Respiratory, thoracic and mediastinal disorders

Epistaxis¹,^†

# participants affected / at risk

3/128 (2.34%)

11/123 (8.94%)

2/64 (3.13%)

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

7/128 (5.47%)

10/123 (8.13%)

1/64 (1.56%)

Skin and subcutaneous tissue disorders

Rash¹,^†

# participants affected / at risk

13/128 (10.16%)

10/123 (8.13%)

1/64 (1.56%)

Skin and subcutaneous tissue disorders

Alopecia¹,^†

# participants affected / at risk

11/128 (8.59%)

9/123 (7.32%)

2/64 (3.13%)

Skin and subcutaneous tissue disorders

Palmar-Plantar Erythrodysaesthesia Syndrome¹,^†

# participants affected / at risk

9/128 (7.03%)

1/123 (0.81%)

2/64 (3.13%)

Skin and subcutaneous tissue disorders

Dry Skin¹,^†

# participants affected / at risk

7/128 (5.47%)

6/123 (4.88%)

3/64 (4.69%)

Skin and subcutaneous tissue disorders

Petechiae¹,^†

# participants affected / at risk

4/128 (3.13%)

7/123 (5.69%)

0/64 (0.00%)

Skin and subcutaneous tissue disorders

Pruritus¹,^†

# participants affected / at risk

5/128 (3.91%)

5/123 (4.07%)

4/64 (6.25%)

Vascular disorders

Hypertension¹,^†

# participants affected / at risk

64/128 (50.00%)

57/123 (46.34%)

4/64 (6.25%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 13.0
2	Term from vocabulary,

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: If a Study Site, or an investigator, requests permission to publish data from this study, any such publication (including oral presentations) is to be agreed with AstraZeneca prior to publication.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Gerard Lynch
Organization:	AstraZeneca
E-mail:	[email protected]

Documents available

Cancer Study Locator (US and Canada only)
Download
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=425&filename=CSR-D8480C00055.pdf
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Contact Backup

AZD2171 Clinical Trials Enquiries

EnquiriesMailbox.AZD2171Trials@target.azemw.net

Investigators

Principal Investigator

Jane Robertson

AstraZeneca

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Cancer Study Locator (US and Canada only)

http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=425&filename=CSR-D8480C00055.pdf

Trial Results Summaries