Clinical Trial: Phase II Study of Axitinib (AG-013736) With Evaluation of the VEGF-pathway in Metastatic, Recurrent or Primary Unresectable Pheochromocytoma/Paraganglioma

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Phase II Study of Axitinib (AG-013736) With Evaluation of the VEGF-pathway in Metastatic, Recurrent or Primary Unresectable Pheochromocytoma/Paraganglioma

Brief Summary:

Background:

  • Most treatments for malignant pheochromocytomas/paragangliomas (PHEO/PGL) are palliative and multidisciplinary. Chemotherapy using the combination of cyclophosphamide, vincristine, and dacarbazine has been successfully utilized in the management of rapidly progressive metastatic PHEO, with more than 50% complete or partial tumor response and more than 70% complete or partial biochemical response.
  • VEGF expression and evidence of angiogenesis has been found in many PHEO/PGL, so it is plausible that interfering with VEGF signaling may result in anti-tumor activity in patients with PHEO/PGL.
  • Axitinib (AG-013736) is an oral, potent and selective inhibitor of vascular endothelial growth factor (VEGF) receptors 1, 2, and 3. Pre-clinical data suggests that the anti-tumor activity of axitinib may result from its anti-angiogenic activity and that this is reversible when treatment is discontinued.
  • Given the known clinical safety and efficacy of axitinib, an assessment of its activity in PHEO/PGL and its impact on the VEGF pathway in PHEO/PGL could provide valuable information.

Objectives:

  • Determine the response rate of metastatic PHEO/PGL to axitinib (AG-013736).
  • Determine the progression-free survival of metastatic PHEO/PGL treated with axitinib (AG-013736).
  • Explore the relationship of potential biological markers of axitinib activity with clinical outcomes.
  • Perform pharmacogenomics analyses of drug metabolism and transport proteins through germline DNA examination.

Background:

  • Most treatments for malignant pheochromocytomas/paragangliomas (PHEO/PGL) are palliative and multidisciplinary. Chemotherapy using the combination of cyclophosphamide, vincristine, and dacarbazine has been successfully utilized in the management of rapidly progressive metastatic PHEO, with more than 50% complete or partial tumor response and more than 70% complete or partial biochemical response.
  • VEGF expression and evidence of angiogenesis has been found in many PHEO/PGL, so it is plausible that interfering with VEGF signaling may result in anti-tumor activity in patients with PHEO/PGL.
  • Axitinib (AG-013736) is an oral, potent and selective inhibitor of vascular endothelial growth factor (VEGF) receptors 1, 2, and 3. Pre-clinical data suggests that the anti-tumor activity of axitinib may result from its anti-angiogenic activity and that this is reversible when treatment is discontinued.
  • Given the known clinical safety and efficacy of axitinib, an assessment of its activity in PHEO/PGL and its impact on the VEGF pathway in PHEO/PGL could provide valuable information.

Objectives:

  • Determine the response rate of metastatic PHEO/PGL to axitinib (AG-013736).
  • Determine the progression-free survival of metastatic PHEO/PGL treated with axitinib (AG-013736).
  • Explore the relationship of potential biological markers of axitinib activity with clinical outcomes.
  • Perform pharmacogenomics analyses of drug metabolism and transport proteins through germline DNA examination.

  • Progression- free survival. [ Time Frame: 3 years ]
  • Examine the extent of activation of the VEGRF pathway inpheochromocytoma/paraganglioma using a semi-quantitativeimmunohistochemistry assay and examine the relationship withresponse to therapy [ Time Frame: 3 years ]
  • Pharmacogenomics analyses [ Time Frame: 3 years ]
  • Perform pharmacokinetic analysis for determination of plasma levels of axitinib [ Time Frame: 3 years ]


    • Original Secondary Outcome:

    • Determine the progression- free survival. [ Time Frame: 4 years ]
    • Pharmacogenomics analyses of drug metabolism and transport proteins through germline DNA examination [ Time Frame: 4 years ]
    • Explore the relationship of potential biological markers of axitinib activity with clinical outcomes. [ Time Frame: 4 years ]


    Information By: National Institutes of Health Clinical Center (CC)

    Dates:
    Date Received: October 19, 2013
    Date Started: October 15, 2013
    Date Completion: October 1, 2017
    Last Updated: May 12, 2017
    Last Verified: March 31, 2017