Neoadjuvant Trial of Nivolumab in Combination With HF10 Oncolytic Viral Therapy in Resectable Stage IIIB, IIIC, IVM1a Melanoma
Condition: Melanoma
MeSH terms: Melanoma
Intervention: Nivolumab; HF10
Intervention description: Nivolumab at a dose of 240 mg given as an IV infusion starting on day 0. It will be given every 14 days for a total of 7 infusions; Then participant will undergo surgery. Nivolumab will then be administered at a flat dose of 480 mg IV every 28 days for up to one year.; 1 x 107th TCID50/mL, intratumoral injection to a single or multiple eligible tumors for a total of 5 mL; on days 0, 7, 14, 21, 28, 42, 56, 70, 84 for a total of 9 injections. All eligible tumors except one will be treated with HF10 up to the maximum volume allowed. The untreated tumor will be used as an untreated control lesion.
Intervention MeSH terms: Nivolumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: This is a single-arm, open label, Phase II
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Resectable Stage IIIB, IIIC, and IVM1a

Summary:

      This is a single-arm, open label, Phase II study evaluating the safety and efficacy of
      neoadjuvant Nivolumab and HF10 in resectable stage IIIB, IIIC, and IVM1a melanoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants must be >18 years or older.

          -  Participants must have stage IIIB, IIIC, or IVM1a (equivalent staging at time of
             enrollment via American Joint Committee on Cancer (AJCC) 7th edition) metastatic
             melanoma which is eligible for complete surgical resection.

          -  Prior systemic, regional and radiation anticancer therapies must have been completed
             at least three months prior to enrollment. Prior therapies (including anti-programmed
             death (PD)-1 inhibitors) are allowed provided three months have elapsed from last
             dose.

          -  Participants must be a candidate for intralesional therapy.

          -  At least 1 injectable cutaneous, subcutaneous, or nodal melanoma lesion > 10 mm in
             longest diameter OR

          -  Multiple injectable melanoma lesions which in aggregate have a longest diameter of >
             10 mm AND

          -  Must have no known bleeding diathesis or coagulopathy that would make intratumoral
             injection unsafe.

          -  Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status
             of 0 or 1.

          -  Serum (LDH) level < 1.5 upper limit of normal (ULN) within 28 days prior to
             enrollment.

          -  Participants have adequate organ function within 28 days prior to enrollment, as
             defined in the protocol

          -  Men and women of childbearing potential must agree to use adequate contraception from
             the time of consent through 7 months after final nivolumab study treatment.

          -  Females of childbearing potential must have a negative urine or serum pregnancy test
             within 1 week prior to the start of treatment.

          -  Participants must be able to provide informed consent and willing to sign an approved
             consent form that conforms to federal and institutional guidelines.

        Exclusion Criteria:

          -  Participants with active visceral, central nervous system, or any bone metastases
             melanoma (Stage IVM1b or IVM1c).

          -  Participants whose primary diagnosis was ocular melanoma.

          -  Participants receiving anti-herpes medication (i.e., acyclovir, famciclovir, or
             valacyclovir) within 1 week prior to initiating HF10 treatment. Participants may not
             require intermittent or chronic systemic (intravenous or oral) treatment with an
             antiherpetic drug other than intermittent topical use.

          -  Participants who have an active herpetic skin lesion(s) or prior complications of
             herpes simplex virus (HSV)-1 infection.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements, as determined by the investigator.

          -  Medical history of autoimmune disease (e.g. Crohn's disease, ulcerative colitis) or
             other disease requiring systemic glucocorticoid or immunosuppressive therapy. Subjects
             who receive daily steroid replacement therapy serve as an exception to this rule.
             Daily prednisone equivalent at doses up to 10 mg would qualify.

          -  Participants with clinically evident Human Immunodeficiency Virus (HIV), Hepatitis B
             Virus (HBV), Hepatitis C Virus (HCV), or Epstein-Barr Virus (EBV) infection are
             excluded.

          -  Pregnant or breast feeding women; women desiring to become pregnant within the
             timeframe of the study are also excluded.