Neoadjuvant Trial of Nivolumab in Combination With HF10 Oncolytic Viral Therapy in Resectable Stage IIIB, IIIC, IVM1a Melanoma

NCT03259425 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: HCI102346
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

Melanoma

Keywords

Resectable Stage IIIB, IIIC, and IVM1a

Outcome Measures

Primary Outcomes (1)

• Pathological Response

  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.

  at time of surgery (12 weeks)

Secondary Outcomes (6)

• 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)

• Radiographic Response: Number of Participants Within Each Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Response Category

  12 weeks from baseline to surgery

• Number of Participants With Complete Surgical Resection

  Within 28 days after Day 84

• Number of Participants With Adverse Events Related to HF10 Treatment

  throughout HF10 treatment (up to 84 days)

Study Arms (1)

Nivolumab and HF10, all participants

EXPERIMENTAL

Drug: Nivolumab; Drug: HF10

Interventions

Nivolumab DRUG

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.

Also known as: OPDIVO

Nivolumab and HF10, all participants

HF10 DRUG

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.

Nivolumab and HF10, all participants

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Utah: lead
• Bristol-Myers Squibb: collaborator
• Takara Bio Inc.: collaborator

Study Sites (1)

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Data Manager, Research Compliance Office
• Organization: Huntsman Cancer Institute

compliance@hci.utah.edu

8015850601

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a single-arm, open label, Phase II

Study Record Dates

• First Submitted: August 18, 2017
• First Posted: August 23, 2017
• Study Start: January 3, 2018
• Primary Completion: September 21, 2018
• Study Completion: September 25, 2020
• Last Updated: June 13, 2022
• Results First Posted: October 10, 2019

Record last verified: 2022-06

Locations

US (1)