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

Phase 2 Study Of The Anti-Angiogenesis Agent AG-013736 In Patients With Metastatic Melanoma

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.

Study Overview

• Status: Completed
• Conditions: Melanoma; Skin Neoplasms
• Intervention / Treatment: Drug: Axitinib [AG-013736]

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Paris Cedex 13, France, 75651
    • Pfizer Investigational Site
• United States
  • California
    • Orange, California, United States, 92868
      • Pfizer Investigational Site
  • Florida
    • Miami Beach, Florida, United States, 33140
      • Pfizer Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Pfizer Investigational Site
    • Boston, Massachusetts, United States, 02115
      • Pfizer Investigational Site
    • Boston, Massachusetts, United States, 02215
      • Pfizer Investigational Site
  • Pennsylvania
    • 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
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Objective Response (OR)	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.	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS)	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").	Baseline until the date of first documented progression or death due to any cause, assessed every 8 weeks up to 147 weeks
Duration of Response (DR)	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.	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
Overall Survival (OS)	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.	Baseline to death due to any cause or at least 1 year after the initial dose for the last treated participant

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Population Pharmacokinetics for Axitinib (AG-013736) Plasma Concentrations	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.	Day 1 (pre-dose), Day 29, Day 57 and then every 8 weeks up to 147 weeks
Plasma Concentrations of Soluble Proteins	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.	Day 1 (pre-dose) and then every 8 weeks up to 147 weeks

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: December 1, 2004
• Primary Completion (Actual): April 1, 2008
• Study Completion (Actual): April 1, 2008

Study Registration Dates

• First Submitted: October 11, 2004
• First Submitted That Met QC Criteria: October 13, 2004
• First Posted (Estimate): October 14, 2004

Study Record Updates

• Last Update Posted (Estimate): June 26, 2012
• Last Update Submitted That Met QC Criteria: June 21, 2012
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: antiangiogenesis; melanoma
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Skin Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Axitinib
• Other Study ID Numbers: A4061015