ZD4054 (Zibotentan) Phase II Non-Small Cell Lung Cancer Study

Study identifier:D4320C00035

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Phase II, Double-blind, Placebo Controlled, Randomised Study to Assess the Efficacy and Safety of ZD4054 (Zibotentan) in Combination with Pemetrexed (Alimta®) vs. Pemetrexed Alone in Patients with Non-small Cell Lung Cancer who Have Failed One Prior Platinum-based Chemotherapy Regimen

Medical condition

Non Small Cell Lung Cancer

Phase

Phase 2

Healthy volunteers

Study drug

ZD4054, Pemetrexed, Placebo

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years +

Date

Study Start Date: 01 Aug 2008

Primary Completion Date: 01 Jan 2010

Study Completion Date: 01 Jan 2010

Study design

Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Apr 2012 by AstraZeneca Pharmaceuticals

Collaborators

Inclusion and exclusion criteria

Location

Research Site

Varna, Bulgaria

Location

research Site

Pleven, Bulgaria

Location

research site

Sofia, Bulgaria

Location

research site

Prague, Czech Republic

Location

research site

Jicin, Czech Republic

Location

research site

Cedex, France

Location

research site

Strasbourg, France

Location

research site

Bucharest, Romania

Arms	Assigned Interventions
Experimental: 1 ZD4054 + Pemetrexed	Drug: ZD4054 10mg oral tablet, once daily Other Name: Zibotentan Drug: Pemetrexed 500mg2/m IV infusion Other Name: Alimta
Placebo Comparator: 2 ZD4054 matched placebo + pemetrexed	Drug: Pemetrexed 500mg2/m IV infusion Other Name: Alimta Drug: Placebo 10mg oral tablet, once daily

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
80 patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) where the histology was not predominantly of squamous type were recruited between 12th August 2008 and 3rd June 2009.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
14 of the 80 enrolled patients were not randomised to treatments groups: 7 patients did not meet one or more of the study inclusion or exclusion criteria, 3 patients failed screening, 2 patients were not included due to investigator decision, 1 patient withdrew consent and 1 patient died.

Reporting Groups

	Description
Placebo + Pemetrexed	Pemetrexed 500 mg/m2 Intravenous (IV) infusion every 21 days + placebo oral tablet once daily
ZD4054 + Pemetrexed	ZD4054 10 mg oral tablet once daily + Pemetrexed 500 mg/m2 IV infusion every 21 days

Participant Flow: Overall Study

	Placebo + Pemetrexed	ZD4054 + Pemetrexed
STARTED	36^[1]	30^[2]
COMPLETED	32^[3]	26^[4]
NOT COMPLETED	4	4
Continuing study treatment	4	4

[1]	Started – Number of patients randomised
[2]	Started – Number of patients randomised
[3]	Completed – Number of patients discontinued study treatment at data cut-off (17th January 2010)
[4]	Completed – Number of patients discontinued study treatment at data cut-off (17th January 2010)

Baseline Characteristics

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

Reporting Groups

	Description
Placebo + Pemetrexed	Pemetrexed 500 mg/m2 Intravenous (IV) infusion every 21 days + placebo oral tablet once daily
ZD4054 + Pemetrexed	ZD4054 10 mg oral tablet once daily + Pemetrexed 500 mg/m2 IV infusion every 21 days

Baseline Measures

	Placebo + Pemetrexed	ZD4054 + Pemetrexed	Total
Number of Participants [units: Participants]	36	30	66
Age Continuous [units: Years] Mean ± Standard Deviation	56.6 ± 12.06	57.5 ± 10.44	57 ± 11.25
Gender, Male/Female [units: Participants]
Female	8	11	19
Male	28	19	47

Outcome Measures

1. Primary Outcome Measure: Time to Death [ Time Frame: Patients were followed up for survival every week for the first 3 weeks then every 3 weeks whilst on study medication until the data cut-off (17th January 2010). ]

Measure Type	Primary
Measure Name	Time to Death
Measure Description	Median time (in days) from randomisation until death using the Kaplan-Meier method (Calculator for survival probability)
Time Frame	Patients were followed up for survival every week for the first 3 weeks then every 3 weeks whilst on study medication until the data cut-off (17th January 2010).
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Placebo + Pemetrexed	Pemetrexed 500 mg/m2 Intravenous (IV) infusion every 21 days + placebo oral tablet once daily
ZD4054 + Pemetrexed	ZD4054 10 mg oral tablet once daily + Pemetrexed 500 mg/m2 IV infusion every 21 days

Measured Values

	Placebo + Pemetrexed	ZD4054 + Pemetrexed
Number of Participants Analyzed [units:participants]	36	30
Time to Death [units: Days] Median (Full Range)	193 (27 to 437)	146 (19 to 427)

No statistical analysis provided for Time to Death

2. Secondary Outcome Measure: Progression-free survival [ Time Frame: Tumour assessments for progression were performed at screening, every 3 weeks, Mandatory Tumour Assessment Visit (19 August 2009 ± 3 days), treatment discontinuation ]

Measure Type	Secondary
Measure Name	Progression-free survival
Measure Description	Median time (in days) from randomisation until disease progression/death using the Kaplan-Meier method
Time Frame	Tumour assessments for progression were performed at screening, every 3 weeks, Mandatory Tumour Assessment Visit (19 August 2009 ± 3 days), treatment discontinuation
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
Placebo + Pemetrexed	Pemetrexed 500 mg/m2 Intravenous (IV) infusion every 21 days + placebo oral tablet once daily
ZD4054 + Pemetrexed	ZD4054 10 mg oral tablet once daily + Pemetrexed 500 mg/m2 IV infusion every 21 days

Measured Values

	Placebo + Pemetrexed	ZD4054 + Pemetrexed
Number of Participants Analyzed [units:participants]	36	30
Progression-free survival [units: Days] Median (Full Range)	87 (27 to 283)	110 (18 to 303)

No statistical analysis provided for Progression-free survival

Serious Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Reporting Groups

	Description
Placebo + Pemetrexed	Pemetrexed 500 mg/m2 Intravenous (IV) infusion every 21 days + placebo oral tablet once daily
ZD4054 + Pemetrexed	ZD4054 10 mg oral tablet once daily + Pemetrexed 500 mg/m2 IV infusion every 21 days

Serious Adverse Events

Placebo + Pemetrexed

ZD4054 + Pemetrexed

Total, serious adverse events

# participants affected / at risk

7/30 (23.33%)

4/36 (11.11%)

Blood and lymphatic system disorders

Anaemia¹,^†

# participants affected / at risk

1/30 (3.33%)

0/36 (0.00%)

Blood and lymphatic system disorders

Febrile Bone Marrow Aplasia¹,^†

# participants affected / at risk

1/30 (3.33%)

0/36 (0.00%)

Blood and lymphatic system disorders

Pancytopenia¹,^†

# participants affected / at risk

0/30 (0.00%)

1/36 (2.78%)

Cardiac disorders

Right Ventricular Failure¹,^†

# participants affected / at risk

1/30 (3.33%)

0/36 (0.00%)

Gastrointestinal disorders

Pancreatitis¹,^†

# participants affected / at risk

1/30 (3.33%)

0/36 (0.00%)

Gastrointestinal disorders

Upper Gastrointestinal Haemorrhage¹,^†

# participants affected / at risk

1/30 (3.33%)

0/36 (0.00%)

General disorders

Adverse Drug Reaction¹,^†

# participants affected / at risk

1/30 (3.33%)

0/36 (0.00%)

General disorders

Asthenia¹,^†

# participants affected / at risk

1/30 (3.33%)

0/36 (0.00%)

Infections and infestations

Erysipelas¹,^†

# participants affected / at risk

0/30 (0.00%)

1/36 (2.78%)

Infections and infestations

Lung Infection¹,^†

# participants affected / at risk

0/30 (0.00%)

1/36 (2.78%)

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

Metastases To Central Nervous System¹,^†

# participants affected / at risk

1/30 (3.33%)

0/36 (0.00%)

Renal and urinary disorders

Renal Failure¹,^†

# participants affected / at risk

1/30 (3.33%)

0/36 (0.00%)

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

0/30 (0.00%)

1/36 (2.78%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 12.1
2	Term from vocabulary,

Other Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Placebo + Pemetrexed	Pemetrexed 500 mg/m2 Intravenous (IV) infusion every 21 days + placebo oral tablet once daily
ZD4054 + Pemetrexed	ZD4054 10 mg oral tablet once daily + Pemetrexed 500 mg/m2 IV infusion every 21 days

Other Adverse Events

Placebo + Pemetrexed

ZD4054 + Pemetrexed

Total, other (not including serious) adverse events

# participants affected / at risk

22/30 (73.33%)

20/36 (55.56%)

Blood and lymphatic system disorders

Anaemia¹,^†

# participants affected / at risk

8/30 (26.67%)

7/36 (19.44%)

Blood and lymphatic system disorders

Neutropenia¹,^†

# participants affected / at risk

5/30 (16.67%)

1/36 (2.78%)

Blood and lymphatic system disorders

Leukopenia¹,^†

# participants affected / at risk

2/30 (6.67%)

0/36 (0.00%)

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

2/30 (6.67%)

5/36 (13.89%)

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

2/30 (6.67%)

1/36 (2.78%)

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

2/30 (6.67%)

2/36 (5.56%)

General disorders

Oedema Peripheral¹,^†

# participants affected / at risk

1/30 (3.33%)

4/36 (11.11%)

General disorders

Fatigue¹,^†

# participants affected / at risk

1/30 (3.33%)

2/36 (5.56%)

Hepatobiliary disorders

Hypertransaminasaemia¹,^†

# participants affected / at risk

2/30 (6.67%)

0/36 (0.00%)

Infections and infestations

Bacterial Infection¹,^†

# participants affected / at risk

2/30 (6.67%)

0/36 (0.00%)

Infections and infestations

Body Temperature Increased¹,^†

# participants affected / at risk

3/30 (10.00%)

2/36 (5.56%)

Infections and infestations

Brain Natriuretic Peptide Increased¹,^†

# participants affected / at risk

0/30 (0.00%)

3/36 (8.33%)

Infections and infestations

Weight Decreased¹,^†

# participants affected / at risk

3/30 (10.00%)

3/36 (8.33%)

Infections and infestations

Alanine Aminotransferase Increased¹,^†

# participants affected / at risk

2/30 (6.67%)

2/36 (5.56%)

Infections and infestations

Aspartate Aminotransferase Increased¹,^†

# participants affected / at risk

1/30 (3.33%)

2/36 (5.56%)

Metabolism and nutrition disorders

Decreased Appetite¹,^†

# participants affected / at risk

1/30 (3.33%)

2/36 (5.56%)

Metabolism and nutrition disorders

Hypokalaemia¹,^†

# participants affected / at risk

2/30 (6.67%)

0/36 (0.00%)

Musculoskeletal and connective tissue disorders

Musculoskeletal Pain¹,^†

# participants affected / at risk

3/30 (10.00%)

0/36 (0.00%)

Musculoskeletal and connective tissue disorders

Back Pain¹,^†

# participants affected / at risk

2/30 (6.67%)

1/36 (2.78%)

Nervous system disorders

Headache¹,^†

# participants affected / at risk

1/30 (3.33%)

3/36 (8.33%)

Psychiatric disorders

Anxiety¹,^†

# participants affected / at risk

2/30 (6.67%)

0/36 (0.00%)

Psychiatric disorders

Insomnia¹,^†

# participants affected / at risk

2/30 (6.67%)

0/36 (0.00%)

Respiratory, thoracic and mediastinal disorders

Cough¹,^†

# participants affected / at risk

0/30 (0.00%)

2/36 (5.56%)

Skin and subcutaneous tissue disorders

Rash¹,^†

# participants affected / at risk

1/30 (3.33%)

3/36 (8.33%)

Skin and subcutaneous tissue disorders

Alopecia¹,^†

# participants affected / at risk

2/30 (6.67%)

2/36 (5.56%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 12.1
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: AstraZeneca can review results communications prior to public release and may within 60 days of receipt require amendments to be made. AstraZeneca can also require that submission or disclosure be delayed for 90 days to allow for the filing of a patent application.

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

https://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=365&filename=CSR-D4320C00035.pdf
Download
CSR-D4320C00035.pdf
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information

800-236-9933

Investigators

Principal Investigator

Thomas Morris

AstraZeneca

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

research Site

research site

research site

research site

research site

research site

research site

https://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=365&filename=CSR-D4320C00035.pdf

CSR-D4320C00035.pdf

Trial Results Summaries