Phase II Neoadjuvant Trial of Nivolumab in Combination With HF10 Oncolytic Viral Therapy in Resectable Stage IIIB, IIIC, IVM1a Melanoma (Neo-NivoHF10)

University of Utah1 site in 1 country7 target enrollmentJanuary 3, 2018

ConditionsMelanoma

InterventionsNivolumab HF10

DrugsNivolumab HF10

Overview

Phase: Phase 2
Intervention: Nivolumab
Conditions: Melanoma
Sponsor: University of Utah
Enrollment: 7
Locations: 1
Primary Endpoint: Pathological Response
Status: Terminated
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief 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.

Registry

clinicaltrials.gov

Start Date

January 3, 2018

End Date

September 25, 2020

Last Updated

3 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

University of Utah

Responsible Party

Sponsor

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
•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

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.

Arms & Interventions

Nivolumab and HF10, all participants

Intervention: Nivolumab

Nivolumab and HF10, all participants

Intervention: HF10

Outcomes

Primary Outcomes

Pathological Response

Time Frame: at time of surgery (12 weeks)

Following 12 weeks of neoadjuvant treatment with nivolumab and HF10, participants underwent definitive surgery. A percent viable tumor was assessed semi-quantitatively in the definitive surgical resection specimen by estimating the proportion of residual tumor in relation to the total tumor area and reported as percentage viability. A pathologic complete response was defined as no viable residual melanoma cells in the surgical specimen. A major pathologic response was defined as \<50% viable tumor cells. A minor pathologic response was defined as 50% or greater viable tumor cells, including specimens that had 100% viability at surgery.

Secondary Outcomes

Recurrence-free Survival: Number of Participants With no Disease Recurrence After Surgery(up to 2 years post-surgery (1 year after end of adjuvant nivolumab, which was given for up to 1 year post-surgery))
Overall Survival: Number of Participants Alive One Year After Completing Adjuvant Nivolumab(up to 2 years post-surgery (1 year after end of adjuvant nivolumab, which was given for up to 1 year post-surgery))
Number of Participants With Adverse Events Related to HF10 Treatment(throughout HF10 treatment (up to 84 days))
Number of Participants With Adverse Events Related to Nivolumab Treatment(throughout nivolumab treatment (up to 84 days prior to surgery and up to 1 year after surgery))
Number of Participants With Complete Surgical Resection(Within 28 days after Day 84)
Radiographic Response: Number of Participants Within Each Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Response Category(12 weeks from baseline to surgery)