Efficacy of XL184 (Cabozantinib) in Advanced Medullary Thyroid Cancer
Condition: Thyroid Cancer
MeSH terms: Thyroid Neoplasms; Thyroid Diseases
Intervention: XL184; Placebo
Intervention description: Gelatin capsules supplied in 25-mg and 100-mg strengths administered orally daily; Gelatin capsules color and size-matched to XL184 capsules administered orally daily
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 330.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Medullary Thyroid Cancer; MTC

Summary:

      The purpose of this research study is to evaluate the progression-free survival (PFS) with
      XL184 as compared with placebo (an inactive substance) in subjects with unresectable, locally
      advanced, or metastatic medullary thyroid cancer (MTC). Subjects will be randomized to
      receive XL184 or placebo in a 2:1 ratio. XL184 is an investigational drug that inhibits
      VEGFR2, MET and RET, kinases implicated in tumor formation, growth and migration.

      The Clinical Steering Committee for this study, comprised of study doctors who specialize in
      medullary thyroid cancer, has provided guidance regarding the design of the study. The
      committee includes: Douglas Ball, MD, Barry Nelkin, PhD, Martin Schlumberger, MD and Steven
      Sherman, MD.
    

Eligibility criteria:

        Inclusion Criteria:

          -  The subject has a histologically confirmed diagnosis of MTC that cannot be removed by
             surgery, is locally advanced, or has spread in the body.

          -  The subject is at least 18 years old.

          -  The subject has an ECOG (Eastern Cooperative Oncology Group) performance status ≤ 2.

          -  The subject has documented worsening of disease (progressive disease) at screening
             compared with a previous CT scan or MRI image done within 14 months of screening.

          -  The subject has recovered from clinically significant adverse events (side effects)
             due to any other medications that were administered prior to randomization.

          -  The subject has adequate organ and bone marrow function.

          -  Subjects who are sexually active (male and female) must agree to use medically
             accepted methods of contraception during the course of the study and for 3 months
             following discontinuation of study treatments.

          -  The subject has no other diagnosis of cancer (unless non-melanoma skin cancer, an
             early form of cervical cancer, or another cancer diagnosed ≥ 2 years previously) and
             currently has no evidence of malignancy (unless non-melanoma skin cancer or an early
             form of cervical cancer).

          -  Female subjects of childbearing potential must have a negative pregnancy test at
             screening.

        Exclusion Criteria:

          -  The subject has received prior treatment for their cancer within 4 weeks of
             randomization (6 weeks for nitrosoureas or mitomycin C).

          -  The subject has received radiation to ≥ 25 % of bone marrow.

          -  The subject has received treatment with other investigational agents (unapproved
             therapies) within 4 weeks of randomization.

          -  The subject has received treatment with XL184.

          -  The subject has brain metastases or spinal cord compression, unless completed
             radiation therapy ≥ 4 weeks prior to randomization and stable without steroid and
             without anti-convulsant treatment for ≥ 10 days.

          -  The subject has a history of clinically significant episodes of vomiting blood or a
             recent history of vomiting > 2.5 mL (about 1/2 teaspoon) of red blood.

          -  The subject has serious illness other than cancer.

          -  The subject is pregnant or breastfeeding.

          -  The subject has an active infection requiring ongoing treatment.

          -  The subject is incapable of understanding and complying with the protocol or unable to
             provide informed consent.