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

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00745875
• Collaborator: (none)
• Enrollment: 66
• Locations: 13
• Arms: 2
• Duration (Months): 17
• Patients Per Site: 5.1
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The aim of this study is to collect initial efficacy and safety data on the use of a new treatment ZD4054 (Zibotentan) when used in combination with pemetrexed (a standard chemotherapy agent) for the treatment of non-small cell lung cancer compared to treatment with pemetrexed alone

Condition or Disease	Intervention/Treatment	Phase
Non Small Cell Lung Cancer; Lung Cancer	Drug: ZD4054; Drug: Pemetrexed; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 66 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Study Start Date: Aug 1, 2008
• Actual Primary Completion Date: Jan 1, 2010
• Actual Study Completion Date: Jan 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 ZD4054 + Pemetrexed	Drug: ZD4054; 10mg oral tablet, once daily; Other Names: Zibotentan ; Drug: Pemetrexed; 500mg2/m IV infusion; Other Names: Alimta
Placebo Comparator: 2 ZD4054 matched placebo + pemetrexed	Drug: Pemetrexed; 500mg2/m IV infusion; Other Names: Alimta ; Drug: Placebo; 10mg oral tablet, once daily

Outcome Measures

Primary Outcome Measures

1. Time to Death [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).]

   Median time (in days) from randomisation until death using the Kaplan-Meier method (Calculator for survival probability)

Secondary Outcome Measures

1. Progression-free Survival [Tumour assessments for progression were performed at screening, every 3 weeks, Mandatory Tumour Assessment Visit (19 August 2009 ± 3 days), treatment discontinuation]

   Median time (in days) from randomisation until disease progression/death using the Kaplan-Meier method

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically or cytologically confirmed locally advanced or metastatic NSCLC on entry into study suitable for pemetrexed therapy

• Patients that meet one of the following criteria: - progressed following one prior platinum-based chemotherapy regimen for locally advanced or metastatic disease; -progressed within 6 months of adjuvant platinum-based chemotherapy

• Life expectancy of > 12 weeks

Exclusion Criteria:

• Prior treatment with pemetrexed in the last 12 months.

• Prior therapy with an ET receptor antagonist

• Any recent surgery, unhealed surgical incision, severe concomitant medical condition (eg, unstable cardiac, hepatic or renal disease) or significant laboratory finding which makes it undesirable for the patient to participate

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	research Site	Pleven		Bulgaria
2	Research Site	Sofia		Bulgaria
3	Research Site	Varna		Bulgaria
4	Research Site	Jicin		Czech Republic
5	Research Site	Prague		Czech Republic
6	Research Site	Cedex		France
7	Research Site	Strasbourg		France
8	Research Site	Bucharest		Romania
9	Research Site	Cluj-Napoca		Romania
10	Research Site	Chernivtsi		Ukraine
11	Research Site	Kiev		Ukraine
12	Research Site	Sumy		Ukraine
13	Research Site	Uzngorod		Ukraine

Sponsors and Collaborators

• AstraZeneca

Investigators

• Study Director: Thomas Morris, MD, AstraZeneca
• Principal Investigator: Christos Chouaid, MD, Prof, Hospital Saint-Antoine, Cedex, France

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT00745875
• Other Study ID Numbers: D4320C00035
• First Posted: Sep 3, 2008
• Last Update Posted: Jun 6, 2012
• Last Verified: Apr 1, 2012

• Keywords provided by AstraZeneca: NSCLC; Phase II; ZD4054; Pemetrexed; Lung Cancer
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Pemetrexed

Study Results

Participant Flow

Recruitment Details	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 Detail	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.

Arm/Group Title	Placebo + Pemetrexed	ZD4054 + Pemetrexed
Arm/Group Description	Pemetrexed 500 mg/m2 Intravenous (IV) infusion every 21 days + placebo oral tablet once daily	ZD4054 10 mg oral tablet once daily + Pemetrexed 500 mg/m2 IV infusion every 21 days
Period Title: Overall Study
STARTED	36	30
COMPLETED	32	26
NOT COMPLETED	4	4

Baseline Characteristics

Arm/Group Title	Placebo + Pemetrexed	ZD4054 + Pemetrexed	Total
Arm/Group Description	Pemetrexed 500 mg/m2 Intravenous (IV) infusion every 21 days + placebo oral tablet once daily	ZD4054 10 mg oral tablet once daily + Pemetrexed 500 mg/m2 IV infusion every 21 days	Total of all reporting groups
Overall Participants	36	30	66
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	56.6 (12.06)	57.5 (10.44)	57 (11.25)
Sex: Female, Male (Count of Participants)
Female	8 22.2%	11 36.7%	19 28.8%
Male	28 77.8%	19 63.3%	47 71.2%

Outcome Measures

1. Primary Outcome

Title	Time to Death
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).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo + Pemetrexed	ZD4054 + Pemetrexed
Arm/Group Description	Pemetrexed 500 mg/m2 Intravenous (IV) infusion every 21 days + placebo oral tablet once daily	ZD4054 10 mg oral tablet once daily + Pemetrexed 500 mg/m2 IV infusion every 21 days
Measure Participants	36	30
Median (Full Range) [Days]	193	146

2. Secondary Outcome

Title	Progression-free Survival
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo + Pemetrexed	ZD4054 + Pemetrexed
Arm/Group Description	Pemetrexed 500 mg/m2 Intravenous (IV) infusion every 21 days + placebo oral tablet once daily	ZD4054 10 mg oral tablet once daily + Pemetrexed 500 mg/m2 IV infusion every 21 days
Measure Participants	36	30
Median (Full Range) [Days]	87	110

Adverse Events

Arm/Group Title	Placebo + Pemetrexed		ZD4054 + Pemetrexed
Arm/Group Description	Pemetrexed 500 mg/m2 Intravenous (IV) infusion every 21 days + placebo oral tablet once daily		ZD4054 10 mg oral tablet once daily + Pemetrexed 500 mg/m2 IV infusion every 21 days
All Cause Mortality
	Placebo + Pemetrexed		ZD4054 + Pemetrexed
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo + Pemetrexed		ZD4054 + Pemetrexed
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/30 (23.3%)		4/36 (11.1%)
Blood and lymphatic system disorders
Anaemia	1/30 (3.3%)		0/36 (0%)
Febrile Bone Marrow Aplasia	1/30 (3.3%)		0/36 (0%)
Pancytopenia	0/30 (0%)		1/36 (2.8%)
Cardiac disorders
Right Ventricular Failure	1/30 (3.3%)		0/36 (0%)
Gastrointestinal disorders
Pancreatitis	1/30 (3.3%)		0/36 (0%)
Upper Gastrointestinal Haemorrhage	1/30 (3.3%)		0/36 (0%)
General disorders
Adverse Drug Reaction	1/30 (3.3%)		0/36 (0%)
Asthenia	1/30 (3.3%)		0/36 (0%)
Infections and infestations
Erysipelas	0/30 (0%)		1/36 (2.8%)
Lung Infection	0/30 (0%)		1/36 (2.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases To Central Nervous System	1/30 (3.3%)		0/36 (0%)
Renal and urinary disorders
Renal Failure	1/30 (3.3%)		0/36 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/30 (0%)		1/36 (2.8%)
Other (Not Including Serious) Adverse Events
	Placebo + Pemetrexed		ZD4054 + Pemetrexed
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/30 (73.3%)		20/36 (55.6%)
Blood and lymphatic system disorders
Anaemia	8/30 (26.7%)		7/36 (19.4%)
Neutropenia	5/30 (16.7%)		1/36 (2.8%)
Leukopenia	2/30 (6.7%)		0/36 (0%)
Gastrointestinal disorders
Nausea	2/30 (6.7%)		5/36 (13.9%)
Constipation	2/30 (6.7%)		1/36 (2.8%)
Vomiting	2/30 (6.7%)		2/36 (5.6%)
General disorders
Oedema Peripheral	1/30 (3.3%)		4/36 (11.1%)
Fatigue	1/30 (3.3%)		2/36 (5.6%)
Hepatobiliary disorders
Hypertransaminasaemia	2/30 (6.7%)		0/36 (0%)
Infections and infestations
Bacterial Infection	2/30 (6.7%)		0/36 (0%)
Body Temperature Increased	3/30 (10%)		2/36 (5.6%)
Brain Natriuretic Peptide Increased	0/30 (0%)		3/36 (8.3%)
Weight Decreased	3/30 (10%)		3/36 (8.3%)
Alanine Aminotransferase Increased	2/30 (6.7%)		2/36 (5.6%)
Aspartate Aminotransferase Increased	1/30 (3.3%)		2/36 (5.6%)
Metabolism and nutrition disorders
Decreased Appetite	1/30 (3.3%)		2/36 (5.6%)
Hypokalaemia	2/30 (6.7%)		0/36 (0%)
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain	3/30 (10%)		0/36 (0%)
Back Pain	2/30 (6.7%)		1/36 (2.8%)
Nervous system disorders
Headache	1/30 (3.3%)		3/36 (8.3%)
Psychiatric disorders
Anxiety	2/30 (6.7%)		0/36 (0%)
Insomnia	2/30 (6.7%)		0/36 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/30 (0%)		2/36 (5.6%)
Skin and subcutaneous tissue disorders
Rash	1/30 (3.3%)		3/36 (8.3%)
Alopecia	2/30 (6.7%)		2/36 (5.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.