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

• ClinicalTrials.gov Identifier: NCT00094107
• Recruitment Status: Completed
• First Posted: October 14, 2004
• Results First Posted: March 30, 2012
• Last Update Posted: June 26, 2012
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

Brief Summary:

This is a Phase 2 study being conducted at multiple centers in the United States and France. Patients having melanoma that has spread to other parts of the body (i.e., metastatic) are eligible to participate. Patients must have disease that has been treated with no more than 1 prior treatment for metastatic disease (prior adjuvant treatment for localized disease does not count as prior treatment for metastatic disease). The purpose of the study is to test whether the angiogenesis inhibitor AG-013736 is an effective treatment for metastatic melanoma as shown by the number of patients in the study who experience significant and durable tumor shrinkage.

Condition or disease	Intervention/treatment	Phase
Melanoma; Skin Neoplasms	Drug: Axitinib [AG-013736]	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 32 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 2 Study Of The Anti-Angiogenesis Agent AG-013736 In Patients With Metastatic Melanoma
• Study Start Date: December 2004
• Actual Primary Completion Date: April 2008
• Actual Study Completion Date: April 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: Axitinib [AG-013736]	Drug: Axitinib [AG-013736]; VEGFR [vascular endothelial growth factor Receptor] and PDGFR [Platelet-Derived Growth Factor Receptor] inhibitor: Single agent AG-013736 starting dose 5 mg BID +/- 20% according to toxicity. Treatment until progression or unacceptable toxicity occurs.

Outcome Measures

Primary Outcome Measures :

1. 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 ]
   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.

Secondary Outcome Measures :

1. 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 ]
   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").
2. 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 ]
   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.
3. 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 ]
   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.

Other Outcome Measures:

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Histologically documented melanoma with metastases
• No more than 1 prior systemic therapy for metastatic disease (prior adjuvant therapy with interferon does not count as prior therapy for metastatic disease)

Exclusion Criteria:

• History of hemoptysis (coughing up of blood)
• Brain metastases

Contacts and Locations

Locations

United States, California

Pfizer Investigational Site

Orange, California, United States, 92868

United States, Florida

Pfizer Investigational Site

Miami Beach, Florida, United States, 33140

United States, Massachusetts

Pfizer Investigational Site

Boston, Massachusetts, United States, 02114

Pfizer Investigational Site

Boston, Massachusetts, United States, 02115

Pfizer Investigational Site

Boston, Massachusetts, United States, 02215

United States, Pennsylvania

Pfizer Investigational Site

Clairton, Pennsylvania, United States, 15025

Pfizer Investigational Site

Greensburg, Pennsylvania, United States, 15601

Pfizer Investigational Site

Johnstown, Pennsylvania, United States, 15901

Pfizer Investigational Site

Pittsburgh, Pennsylvania, United States, 15232-1305

Pfizer Investigational Site

Pittsburgh, Pennsylvania, United States, 15232

Pfizer Investigational Site

Wexford, Pennsylvania, United States, 15090

France

Pfizer Investigational Site

Paris Cedex 13, France, 75651

Sponsors and Collaborators

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

More Information

Additional Information:

To obtain contact information for a study center near you, click here. 

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00094107
• Other Study ID Numbers: A4061015
• First Posted: October 14, 2004
• Results First Posted: March 30, 2012
• Last Update Posted: June 26, 2012
• Last Verified: June 2012

Keywords provided by Pfizer:

melanoma; antiangiogenesis

Additional relevant MeSH terms:

Melanoma; Skin Neoplasms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Neoplasms by Site; Skin Diseases; Axitinib; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action