Cabozantinib in Recurrent/Metastatic Merkel Cell Carcinoma
Condition: Merkel Cell Carcinoma; Skin Cancer
MeSH terms: Carcinoma, Merkel Cell; Carcinoma; Skin Neoplasms
Intervention: Cabozantinib
Intervention description: oral administration
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Merkel Cell Carcinoma; Skin Cancer

Summary:

      This is an open-label, non-randomized, phase 2 study to assess the feasibility of using
      cabozantinib in recurrent/metastatic Merkel Cell Carcinoma patients that progressed after
      platinum-based therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Must have histologically or cytologically confirmed Merkel Cell Carcinoma that is
             metastatic or unresectable and for which standard curative measures do not exist or
             are no longer effective

          -  Must have measurable disease, defined as at least one lesion that can be accurately
             measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm with
             conventional techniques or as ≥10 mm with spiral CT scan (see section 10 for the
             evaluation of measureable disease). Tumors within a previously irradiated field will
             be designated as "non-target" lesions unless progression is documented

          -  Must have had one prior platinum-based chemotherapeutic regimen for management of
             primary disease containing carboplatin, cisplatin or another organoplatinum compound.
             Patients are also eligible if they received curative intent platinum-based therapy and
             progressed within a year of therapy

          -  No prior MET inhibitor is allowed

          -  At least 2 weeks since prior chemotherapy or radiation therapy. At least 3 weeks since
             prior biologics or investigational agents

          -  Recovery from effects of recent treatment to baseline or CTCAE ≤ grade 1 toxicity from
             all prior therapies except alopecia and other non-clinically significant AEs

          -  Participants must be ≥18 years of age

          -  ECOG performance status ≤1

          -  Participants must have normal organ and marrow function

          -  Women of child-bearing potential and men must agree to use adequate contraception
             prior to study entry and for the duration of study participation

          -  Ability to understand and the willingness to sign a written informed consent document

          -  Collection of archival tissue specimens for confirmation of Merkel Cell Carcinoma

        Exclusion Criteria:

          -  Participants who have had chemotherapy or radiotherapy within 2 weeks prior to
             entering the study or those who have not recovered from adverse events due to agents
             administered more than 2 weeks earlier

          -  Participants may not be receiving any biologics or investigational agents within 3
             weeks

          -  The subject has active brain metastases or epidural disease

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to cabozantinib

          -  Has prothrombin time (PT)/ International Normalized Ratio (INR) or partial
             thromboplastin time (PTT) test ≥ 1.3 the institutional ULN within 7 days before the
             first dose of study treatment, unless PT/PTT prolongation known to be secondary to
             conditions not associated with increased bleeding risk (as on antiphospholipid
             antibody syndrome)

          -  Requires concomitant treatment, in therapeutic doses, with anticoagulants

          -  Active bleeding or pathologic conditions that carry high risk of bleeding

          -  Have experienced clinically significant gastrointestinal bleeding within 6 months
             before first dose of study treatment

          -  Requires chronic concomitant treatment of strong CYP3A4 inducers

          -  Is unable or unwilling to swallow tablets

          -  Has a corrected QT interval calculated by the Fridericia formula (QTcF)>500 ms within
             28 days before initiation of cabozantinib

          -  Has evidence of tumor invading the GI tract or any evidence of endotracheal or
             endobronchial tumor within 28 days before the first dose of cabozantinib

          -  Has radiographic evidence of cavitating pulmonary lesion(s)

          -  Has uncontrolled, significant intercurrent or recent illness

          -  Other disorders associated with a high risk of fistula formation including PEG tube
             placement within 3 months before the first dose of study therapy

          -  History of major surgery within 3 months or minor surgery within 1 month of the first
             dose of cabozantinib

          -  Pregnant women

          -  Individuals with a history of other malignancies are eligible if they have been
             disease-free for at least 5 years and are deemed by the investigator to be at low risk
             for recurrence of that malignancy

          -  HIV-positive individuals on combination antiretroviral therapy