Anti-Angiogenesis Agent AG-013736 In Patients With Metastatic Melanoma

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

Pfizer

ClinicalTrials.gov Identifier:

NCT00094107

First received: October 11, 2004

Last updated: June 21, 2012

Last verified: June 2012

History of Changes

Results First Received: February 25, 2012

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Single Group Assignment; Masking: Open Label; Primary Purpose: Treatment
Conditions:	Melanoma Skin Neoplasms
Intervention:	Drug: Axitinib [AG-013736]

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
Axitinib	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.

Participant Flow: Overall Study

	Axitinib
STARTED	32
COMPLETED	0
NOT COMPLETED	32
Lack of Efficacy	23
Death	5
Adverse Event	3
Withdrawal due to Disease Progression	1

Baseline Characteristics

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Reporting Groups

	Description
Axitinib	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.

Baseline Measures

	Axitinib
Number of Participants [units: participants]	32
Age [units: Years] Mean ± Standard Deviation	62.40 ± 15.56
Gender [units: Participants]
Female	15
Male	17

Outcome Measures

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1. Primary:

Percentage of Participants With Objective Response (OR) [ 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 147 weeks ]

Measure Type	Primary
Measure Title	Percentage of Participants With Objective Response (OR)
Measure 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 147 weeks
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.
Study population included all participants who received at least 1 dose of study medication and had at least one baseline efficacy assessment.

Reporting Groups

	Description
Axitinib	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.

Measured Values

	Axitinib
Number of Participants Analyzed [units: participants]	32
Percentage of Participants With Objective Response (OR) [units: Percentage of participants] Number ( 95% Confidence Interval )	18.8 ( 7.2 to 36.4 )

No statistical analysis provided for Percentage of Participants With Objective Response (OR)

2. Secondary:

Progression-free Survival (PFS) [ Time Frame: Baseline until the date of first documented progression or death due to any cause, assessed every 8 weeks up to 147 weeks ]

Measure Type	Secondary
Measure Title	Progression-free Survival (PFS)
Measure 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 147 weeks
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.
Study population included all participants who received at least 1 dose of study medication and had at least one baseline efficacy assessment.

Reporting Groups

	Description
Axitinib	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.

Measured Values

	Axitinib
Number of Participants Analyzed [units: participants]	32
Progression-free Survival (PFS) [units: Days] Median ( 95% Confidence Interval )	117.5 ( 69.0 to 204.0 )

No statistical analysis provided for Progression-free Survival (PFS)

3. Secondary:

Duration of Response (DR) [ 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 147 weeks ]

Measure Type	Secondary
Measure Title	Duration of Response (DR)
Measure 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 147 weeks
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.
Subgroup of participants from the study population with a confirmed objective tumor response (CR or PR).

Reporting Groups

	Description
Axitinib	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.

Measured Values

	Axitinib
Number of Participants Analyzed [units: participants]	5
Duration of Response (DR) [units: Days] Median ( 95% Confidence Interval )	179.0 ( 151.0 to 516.0 )

No statistical analysis provided for Duration of Response (DR)

4. Secondary:

Overall Survival (OS) [ Time Frame: Baseline to death due to any cause or at least 1 year after the initial dose for the last treated participant ]

Measure Type	Secondary
Measure Title	Overall Survival (OS)
Measure 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
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.
Study population included all participants who received at least 1 dose of study medication.

Reporting Groups

	Description
Axitinib	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.

Measured Values

	Axitinib
Number of Participants Analyzed [units: participants]	32
Overall Survival (OS) [units: Days] Median ( 95% Confidence Interval )	200.5 ( 157.0 to 274.0 )

No statistical analysis provided for Overall Survival (OS)

5. Other Pre-specified:

Population Pharmacokinetics for Axitinib (AG-013736) Plasma Concentrations [ Time Frame: Day 1 (pre-dose), Day 29, Day 57 and then every 8 weeks up to 147 weeks ]

Measure Type	Other Pre-specified
Measure Title	Population Pharmacokinetics for Axitinib (AG-013736) Plasma Concentrations
Measure 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 147 weeks
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.
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 (AG-013736) Phase 2 studies would be pooled together in a separate report.

Reporting Groups

	Description
Axitinib	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.

Measured Values

	Axitinib
Number of Participants Analyzed [units: participants]	0
Population Pharmacokinetics for Axitinib (AG-013736) Plasma Concentrations [units: ng/mL] Mean ± Standard Deviation

No statistical analysis provided for Population Pharmacokinetics for Axitinib (AG-013736) Plasma Concentrations

6. Other Pre-specified:

Plasma Concentrations of Soluble Proteins [ Time Frame: Day 1 (pre-dose) and then every 8 weeks up to 147 weeks ]

Measure Type	Other Pre-specified
Measure Title	Plasma Concentrations of Soluble Proteins
Measure 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 147 weeks
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.
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.

Reporting Groups

	Description
Axitinib	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.

Measured Values

	Axitinib
Number of Participants Analyzed [units: participants]	0
Plasma Concentrations of Soluble Proteins [units: Ratio] Mean ± Standard Deviation

No statistical analysis provided for Plasma Concentrations of Soluble Proteins

Serious Adverse Events

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Other Adverse Events

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More Information

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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: 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.

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
Population pharmacokinetic 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 (AG-013736) Phase 2 studies would be pooled together in a separate report.

Results Point of Contact:

Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.gov_Inquiries@pfizer.com

No publications provided

Responsible Party:	Pfizer
ClinicalTrials.gov Identifier:	NCT00094107 History of Changes
Other Study ID Numbers:	A4061015
Study First Received:	October 11, 2004
Results First Received:	February 25, 2012
Last Updated:	June 21, 2012
Health Authority:	United States: Food and Drug Administration

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