Cabozantinib for Adults With Advanced Soft Tissue Sarcoma
Condition: Refractory Soft Tissue Sarcomas
MeSH terms: Sarcoma
Study type: Interventional
Phase: Phase 2

Summary: 
      Background:

      - Cabozantinib is a cancer treatment drug that blocks the growth of new blood vessels in
      tumors. It can also block a chemical on tumor cells that allows the cells to grow. A similar
      drug, pazopanib, is used to treat types of cancer known as sarcomas. Researchers want to see
      if cabozantinib can be an effective treatment for types of soft tissue sarcoma that have not
      responded to earlier treatments.

      Objectives:

      - To test the effectiveness of cabozantinib for soft tissue sarcomas that have not responded
      to standard treatments.

      Eligibility:

      - Individuals at least 18 years of age who have soft tissue sarcomas that have not responded
      to standard treatments.

      Design:

        -  Participants will be screened with a physical exam and medical history. Blood samples
           will be collected. Imaging studies and other tests will be used to study the tumor
           before the start of treatment.

        -  Participants will take cabozantinib tablets daily for 28-day cycles of treatment. The
           tablets should be taken whole on an empty stomach.

        -  Treatment will be monitored with frequent blood tests and imaging studies.

        -  Participants will continue to take cabozantinib for as long as the tumor does not become
           worse and the side effects are not too severe.
    

Detailed description: 
      Background:

        -  Soft tissue sarcomas (STS) are a relatively rare heterogeneous group of tumors that
           constitute about 1% of adult cancers.

        -  The mainstay of treatment for advanced disease has been palliative chemotherapy with a
           median overall survival of approximately 12 months. This has not changed considerably in
           the past years and there is an unmet need for newer targeted therapies.

        -  Vascular endothelial growth factor (VEGF) levels are elevated in patients with STS and
           various sarcoma cell lines express high levels of activated c-Met receptor.

        -  We hypothesize that dual targeting of the VEGF and mesenchymal-epithelial transition
           factor (c-MET) pathways with cabozantinib would result in clinical benefit in patients
           with soft tissue sarcoma.

      Objectives:

      Primary:

        -  Assess the response rate (Complete Response (CR)+Partial Response (PR) of cabozantinib
           in patients with soft tissue sarcomas.

        -  Assess the 6 month progression free survival (PFS) of cabozantinib in soft tissue
           sarcomas.

      Secondary:

      -Determine and compare circulating levels of hepatocyte growth factor (HGF), soluble MET
      (sMET), VEGF-A, and soluble vascular endothelial growth factor receptor 2 (VEGFR2) (sVEGFR2)
      prior to and following administration of cabozantinib.

      Eligibility:

        -  Patients must have had disease progression following one line of standard therapy

        -  Age greater than or equal to 18 years.

        -  Adequate organ function.

      Design:

        -  All patients will receive cabozantinib at 60 mg by mouth (PO) daily in 4 week cycles.

        -  Tumor response evaluations by imaging will be done every 2 cycles (less frequently for
           patients on study more than one year).

        -  The study will be conducted as a dual-endpoint two-stage Phase II trial to target
           objective tumor response rate (CR+PR) of 30% against an unacceptably low rate of 10%,
           and 6-month PFS rate of 65% against an unacceptably low rate of 45% (corresponding to
           median PFS of 9.6 vs. 5.2 months).

        -  The trial will accrue up to 55 patients.
    

Intervention name(s): Cabozantinib
Intervention type(s): Drug
Intervention description(s): Cabozantinib inhibits multiple receptor tyrosine kinases (RTKs) implicated in tumor growth, metastasis, and angiogenesis, and targets primarily mesenchymal-epithelial transition factor (MET) and vascular endothelial growth factor receptor 2 (VEGFR2).
Other intervention name(s): Cometriq
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Dual Inhibitor of MET and VEGFR; XL184; Metastatic Refractory; Soft Tissue Sarcoma; Rare Heterogeneous Tumor