Clinical Trial: Trial of X4P-001 in Patients With Advanced Renal Cell Carcinoma

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase 1/2 Trial of X4P-001 as Single Agent and in Combination With Axitinib in Patients With Advanced Renal Cell Carcinoma

Brief Summary: The purpose of the study is to test different doses of X4P-001 given alone and in combination with axitinib in patients diagnosed with advanced renal cell carcinoma. The goals of the study are to determine the safety and tolerability of X4P-001, as well as the potential effect it may have on the body and the cancer tumor.

Detailed Summary:

X4P-001 is an orally bioavailable CXCR4 antagonist that has demonstrated activity in various tumor models. CXCR4 (C-X-C chemokine receptor type 4) is the receptor for CXCL12 (C-X-C chemokine ligand type 12). CXCL12 has potent chemotactic activity for lymphocytes and MDSCs (myeloid-derived suppressor cells), and is important in homing of hematopoietic stem cells to the bone marrow. CXCR4 is also expressed and active on multiple types of human cancers, including ccRCC, ovarian cancer, and melanoma, and increased expression of CXCR4 on tumor cells has been associated with significantly decreased overall patient survival.

Multiple observations implicate the CXCL12/CXCR4 axis in contributing to the lack (or loss) of tumor responsiveness to angiogenesis inhibitors (also referred to as "angiogenic escape"). In animal cancer models, interference with CXCR4 function has been demonstrated to disrupt the tumor microenvironment and unmask the tumor to immune attack by multiple mechanisms, including:

  • Eliminating tumor re-vascularization
  • Decreasing the infiltration of MDSCs
  • Increasing the ratio of CD8+ T cells to Treg cells

The hypothesis is that effective CXCR4 antagonism by X4P-001 would be of potential benefit in patients with advanced ccRCC and other cancers by multiple mechanisms:

  • Decreased recruitment of MDSCs, resulting in increased anti-tumor immune attack
  • Sustained decrease in neoangiogenesis and tumor vascular supply
  • Interference with the autocrine effect of increased expression by ccRCC of both CXCR4 and CXCL12
    Sponsor: X4 Pharmaceuticals

    Current Primary Outcome: Incidence of Treatment-Emergent Adverse Events (Safety and tolerability) [ Time Frame: Up to 80 weeks, from time of enrollment through study completion or early termination ]

    Safety assessments including vital signs, physical exams, laboratory tests, and adverse event monitoring


    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • Objective Response Rate [ Time Frame: Up to 80 weeks, from time of enrollment through study completion or early termination ]
      The treatment effect of X4P-001, as single agent and in combination with axitinib, will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 to determine tumor response.
    • Disease Control Rate [ Time Frame: Up to 80 weeks, from time of enrollment through study completion or early termination ]
      The treatment effect of X4P-001, as single agent and in combination with axitinib, will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 to determine the disease control rate.
    • Progression Free Survival [ Time Frame: Up to 80 weeks, from time of enrollment through study completion or early termination ]
      The treatment effect of X4P-001, as single agent and in combination with axitinib, will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 to determine progression free survival time.
    • Maximum Plasma Concentration (Cmax) [ Time Frame: Up to 8 hrs post-dose ]
      Cmax data will be collected to determine the pharmacokinetics of escalating dose levels of X4P-001 administered orally.
    • Area Under the Curve (AUC) [ Time Frame: Up to 8 hrs post-dose ]
      AUC data will be collected to determine the pharmacokinetics of escalating dose levels of X4P-001 administered orally.
    • Minimum Plasma Concentration (Cmin) [ Time Frame: Up to 7 weeks ]
      Cmin data will be collected to determine the pharmacokinetics of escalating dose levels of X4P-001 administered orally.


    Original Secondary Outcome: Same as current

    Information By: X4 Pharmaceuticals

    Dates:
    Date Received: January 20, 2016
    Date Started: January 2016
    Date Completion:
    Last Updated: February 8, 2017
    Last Verified: February 2017