Anti-angiogenesis Agent AG-013736 in Patients With Advanced Non-Small Cell Lung Cancer

• ClinicalTrials.gov Identifier: NCT00094094
• Recruitment Status: Completed
• First Posted: October 14, 2004
• Results First Posted: March 16, 2012
• Last Update Posted: June 26, 2012
• Sponsor: Pfizer
• Information provided by: Pfizer

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Lung Neoplasms; Carcinoma, Non-small Cell Lung
• Intervention: Drug: axitinib
• Enrollment: 32

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Axitinib
Arm/Group Description	Axitinib (AG-013736) tablet administered orally at a dose of 5 milligram (mg) twice daily (BID) in cycles of 4 weeks. Treatment was administered continuously until progression or unacceptable toxicity occurred or the participant withdrew consent.
Period Title: Overall Study
Started	32
Completed	0
Not Completed	32
Reason Not Completed
Death	2
Lack of Efficacy	23
Adverse Event	7

Baseline Characteristics

Arm/Group Title		Axitinib
Arm/Group Description		Axitinib (AG-013736) tablet administered orally at a dose of 5 mg BID in cycles of 4 weeks. Treatment was administered continuously until progression or unacceptable toxicity occurred or the participant withdrew consent.
Overall Number of Baseline Participants		32
Baseline Analysis Population Description		[Not Specified]
Age Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	32 participants
		64.1 (12.3)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	32 participants
	Female	13 40.6%
	Male	19 59.4%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Objective Response (OR)
Description	Percentage of participants with OR based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. CR are defined as the disappearance of all lesions (target and/or non target). PR are those with at least 30 percent (%) decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.
Time Frame	Baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 8 weeks up to 98 weeks

Outcome Measure Data

Analysis Population Description

Study population included all participants who enrolled and received treatment.

Arm/Group Title	Axitinib
Arm/Group Description:	Axitinib (AG-013736) tablet administered orally at a dose of 5 mg BID in cycles of 4 weeks. Treatment was administered continuously until progression or unacceptable toxicity occurred or the participant withdrew consent.
Overall Number of Participants Analyzed	32
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	9.4; (2.0 to 25.0)

2. Secondary Outcome

Title	Progression-Free Survival (PFS)
Description	Time in days from start of study treatment to first documentation of objective tumor progression or death due to any cause. PFS was calculated as first event date minus the date of first dose of study medication plus 1. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was "Death").
Time Frame	Baseline until the date of first documented progression or death due to any cause, assessed every 8 weeks up to 98 weeks

Outcome Measure Data

Analysis Population Description

Study population included all participants who enrolled and received treatment.

Arm/Group Title	Axitinib
Arm/Group Description:	Axitinib (AG-013736) tablet administered orally at a dose of 5 mg BID in cycles of 4 weeks. Treatment was administered continuously until progression or unacceptable toxicity occurred or the participant withdrew consent.
Overall Number of Participants Analyzed	32
Median (95% Confidence Interval); Unit of Measure: Days
	148; (109 to 213)

3. Secondary Outcome

Title	Duration of Response (DR)
Description	Time in days from the first documentation of objective tumor response to objective tumor progression or death due to any cause. Duration of tumor response was calculated as the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1. DR was calculated for the subgroup of participants with a confirmed objective tumor response.
Time Frame	Baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 8 weeks up to 98 weeks

Outcome Measure Data

Analysis Population Description

Subgroup of participants from the study population with a confirmed objective tumor response (CR or PR).

Arm/Group Title	Axitinib
Arm/Group Description:	Axitinib (AG-013736) tablet administered orally at a dose of 5 mg BID in cycles of 4 weeks. Treatment was administered continuously until progression or unacceptable toxicity occurred or the participant withdrew consent.
Overall Number of Participants Analyzed	3
Median (95% Confidence Interval); Unit of Measure: Days
	252; (179 to 322)

4. Secondary Outcome

Title	Overall Survival (OS)
Description	Time in days from the start of study treatment to date of death due to any cause. OS was calculated as the death date minus the date of first dose of study medication plus 1. Death was determined from AE data (where outcome was death) or from follow-up contact data (where the participant current status was death). For participants who were alive, overall survival was censored at the last contact.
Time Frame	Baseline to death due to any cause or at least 1 year after the initial dose for the last treated participant

Outcome Measure Data

Analysis Population Description

Study population included all participants who enrolled and received treatment.

Arm/Group Title	Axitinib
Arm/Group Description:	Axitinib (AG-013736) tablet administered orally at a dose of 5 mg BID in cycles of 4 weeks. Treatment was administered continuously until progression or unacceptable toxicity occurred or the participant withdrew consent.
Overall Number of Participants Analyzed	32
Median (95% Confidence Interval); Unit of Measure: Days
	450 [1]; (326 to NA)

[1]

Upper limit of confidence interval was not estimable due to the high number of participants censored for survival.

5. Other Pre-specified Outcome

Title	Population Pharmacokinetics for Axitinib (AG-013736) Plasma Concentrations
Description	Population pharmacokinetic analysis involved mixed effects modeling using nonlinear mixed effects modeling (NONMEM) software. The intent of this analysis was to establish a basic population pharmacokinetic model for axitinib (AG-013736) and to determine inter-individual and residual variability in population (oral) clearance, and volume of distribution of drug. Relationship of demographic variables (gender, age, body weight, height and ethnicity), concomitant medications and measures of altered hepatic and renal function were examined by fitting measured axitinib (AG-013736) concentrations.
Time Frame	Day 1 (pre-dose), Day 29, Day 57 and then every 8 weeks up to 98 weeks

Outcome Measure Data

Analysis Population Description

Population pharmacokinetic values were not summarized as descriptive statistics since the data was not available for the single study and data for all the axitinib Phase 2 studies would be pooled together in a separate report.

Arm/Group Title	Axitinib
Arm/Group Description:	Axitinib (AG-013736) tablet administered orally at a dose of 5 mg BID in cycles of 4 weeks. Treatment was administered continuously until progression or unacceptable toxicity occurred or the participant withdrew consent.
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

6. Other Pre-specified Outcome

Title	Plasma Concentrations of Soluble Proteins
Description	Plasma concentrations of soluble proteins (vascular endothelial growth factor [VEGF], placental growth factor [PlGF] and soluble vascular endothelial growth factor receptor-2 [sVEGFR2]) may be associated with tumor angiogenesis or tumor physiology and may correlate with efficacy or biological activity. It is presented as ratio to baseline, which is obtained by dividing the plasma soluble protein concentration at each time point by its concentration at baseline.
Time Frame	Day 1 (pre-dose) and then every 8 weeks up to 98 weeks

Outcome Measure Data

Analysis Population Description

Ratio to baseline values for plasma soluble proteins were not summarized as descriptive statistics since the data was not available for the single study and data for all the axitinib Phase 2 studies would be pooled together in a separate report.

Arm/Group Title	Axitinib
Arm/Group Description:	Axitinib (AG-013736) tablet administered orally at a dose of 5 mg BID in cycles of 4 weeks. Treatment was administered continuously until progression or unacceptable toxicity occurred or the participant withdrew consent.
Overall Number of Participants Analyzed	0

No data displayed because Outcome Measure has zero total analyzed.

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Axitinib
Arm/Group Description	Axitinib (AG-013736) tablet administered orally at a dose of 5 mg BID in cycles of 4 weeks. Treatment was administered continuously until progression or unacceptable toxicity occurred or the participant withdrew consent.
All-Cause Mortality
	Axitinib
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Axitinib
	Affected / at Risk (%)
Total	16/32 (50.00%)
Cardiac disorders
Acute coronary syndrome * 1	1/32 (3.13%)
Bradycardia, not otherwise specified (NOS) * 1	1/32 (3.13%)
Gastrointestinal disorders
Appendicitis * 1	1/32 (3.13%)
Colitis NOS * 1	1/32 (3.13%)
Diarrhoea haemorrhagic * 1	1/32 (3.13%)
Dysphagia * 1	1/32 (3.13%)
Large intestinal ulcer * 1	1/32 (3.13%)
Oesophageal stenosis acquired * 1	1/32 (3.13%)
Rectal haemorrhage * 1	1/32 (3.13%)
General disorders
Disease progression NOS * 1	5/32 (15.63%)
General physical health deterioration * 1	1/32 (3.13%)
Infections and infestations
Bronchitis acute NOS * 1	1/32 (3.13%)
Infection NOS * 1	1/32 (3.13%)
Pneumonia NOS * 1	1/32 (3.13%)
Metabolism and nutrition disorders
Dehydration * 1	2/32 (6.25%)
Hyperkalaemia * 1	1/32 (3.13%)
Nervous system disorders
Ataxia * 1	1/32 (3.13%)
Cerebrovascular accident * 1	1/32 (3.13%)
Convulsions NOS * 1	1/32 (3.13%)
Transient ischaemic attack * 1	1/32 (3.13%)
Psychiatric disorders
Confusion * 1	3/32 (9.38%)
Renal and urinary disorders
Renal failure acute * 1	1/32 (3.13%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive airways disease exacerbated * 1	1/32 (3.13%)
Cough * 1	1/32 (3.13%)
Dyspnoea NOS * 1	2/32 (6.25%)
Dyspnoea exacerbated * 1	1/32 (3.13%)
Vascular disorders
Hypotension NOS * 1	1/32 (3.13%)
Inferior vena caval obstruction * 1	1/32 (3.13%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 13.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Axitinib
	Affected / at Risk (%)
Total	31/32 (96.88%)
Blood and lymphatic system disorders
Anaemia * 1	3/32 (9.38%)
Cardiac disorders
Tachycardia * 1	4/32 (12.50%)
Endocrine disorders
Hypothyroidism * 1	2/32 (6.25%)
Gastrointestinal disorders
Abdominal pain * 1	4/32 (12.50%)
Abdominal pain upper * 1	3/32 (9.38%)
Constipation * 1	6/32 (18.75%)
Diarrhoea * 1	15/32 (46.88%)
Dyspepsia * 1	7/32 (21.88%)
Dysphagia * 1	4/32 (12.50%)
Flatulence * 1	2/32 (6.25%)
Glossodynia * 1	3/32 (9.38%)
Nausea * 1	15/32 (46.88%)
Oral discomfort * 1	2/32 (6.25%)
Oral pain * 1	4/32 (12.50%)
Stomatitis * 1	2/32 (6.25%)
Vomiting * 1	10/32 (31.25%)
General disorders
Chest pain * 1	4/32 (12.50%)
Fatigue * 1	27/32 (84.38%)
Gait disturbance * 1	2/32 (6.25%)
Mucosal inflammation * 1	5/32 (15.63%)
Oedema peripheral * 1	5/32 (15.63%)
Pain * 1	2/32 (6.25%)
Infections and infestations
Bronchitis * 1	2/32 (6.25%)
Rhinitis * 1	2/32 (6.25%)
Upper respiratory tract infection * 1	7/32 (21.88%)
Injury, poisoning and procedural complications
Traumatic haematoma * 1	2/32 (6.25%)
Investigations
Alanine aminotransferase increased * 1	2/32 (6.25%)
Blood creatinine increased * 1	2/32 (6.25%)
Weight decreased * 1	11/32 (34.38%)
Metabolism and nutrition disorders
Degreased appetite * 1	19/32 (59.38%)
Dehydration * 1	3/32 (9.38%)
Hyperglycaemia * 1	2/32 (6.25%)
Hypoglycaemia * 1	2/32 (6.25%)
Hypokalaemia * 1	4/32 (12.50%)
Hypomagnesaemia * 1	3/32 (9.38%)
Hyponatraemia * 1	4/32 (12.50%)
Musculoskeletal and connective tissue disorders
Arthralgia * 1	8/32 (25.00%)
Back pain * 1	3/32 (9.38%)
Bone pain * 1	2/32 (6.25%)
Muscular weakness * 1	5/32 (15.63%)
Musculoskeletal pain * 1	4/32 (12.50%)
Myalgia * 1	3/32 (9.38%)
Pain in extremity * 1	4/32 (12.50%)
Nervous system disorders
Ataxia * 1	2/32 (6.25%)
Dizziness * 1	3/32 (9.38%)
Headache * 1	8/32 (25.00%)
Neuropathy peripheral * 1	3/32 (9.38%)
Somnolence * 1	2/32 (6.25%)
Psychiatric disorders
Anxiety * 1	2/32 (6.25%)
Confusional state * 1	2/32 (6.25%)
Depression * 1	2/32 (6.25%)
Insomnia * 1	4/32 (12.50%)
Renal and urinary disorders
Proteinuria * 1	6/32 (18.75%)
Urinary retention * 1	2/32 (6.25%)
Respiratory, thoracic and mediastinal disorders
Cough * 1	11/32 (34.38%)
Dysphonia * 1	12/32 (37.50%)
Dyspnoea * 1	10/32 (31.25%)
Epistaxis * 1	4/32 (12.50%)
Haemoptysis * 1	3/32 (9.38%)
Hypoxia * 1	2/32 (6.25%)
Oropharyngeal pain * 1	2/32 (6.25%)
Skin and subcutaneous tissue disorders
Alopecia * 1	3/32 (9.38%)
Dry skin * 1	3/32 (9.38%)
Rash * 1	5/32 (15.63%)
Rash erythematous * 1	2/32 (6.25%)
Vascular disorders
Hypertension * 1	10/32 (31.25%)
Hypotension * 1	2/32 (6.25%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 13.1

Limitations and Caveats

Population pharmacokinetics and plasma concentrations of soluble proteins were not presented, as the data was not available for the single study and data for all the axitinib Phase 2 studies would be pooled together in a separate report.

More Information

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.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.

Results Point of Contact

• Name/Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.
• Phone: 1-800-718-1021
• EMail: ClinicalTrials.gov_Inquiries@pfizer.com

• ClinicalTrials.gov Identifier: NCT00094094
• Other Study ID Numbers: A4061011
• First Submitted: October 11, 2004
• First Posted: October 14, 2004
• Results First Submitted: February 25, 2012
• Results First Posted: March 16, 2012
• Last Update Posted: June 26, 2012