A Study of Combination Treatment With HF10 and Ipilimumab in Patients With Unresectable or Metastatic Melanoma

NCT02272855 | Completed Phase 2 FDA Drug

• 1 other identifier: T14-10682
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 8

Brief Summary

The purpose of this study is to determine if HF10 in combination with ipilimumab is effective in patients with stages IIIB, IIIC, or IV unresectable or metastatic melanoma.

Conditions

Malignant Melanoma

Keywords

HF10; HSV-1; Ipilimumab; Oncolytic virus; Phase II; Stage IIIB melanoma; Stage IIIC melanoma; Stage IV melanoma; Unresectable malignant melanoma; Metastatic malignant melanoma; Combination treatment; Intratumoral injection

Outcome Measures

Primary Outcomes (1)

• Best overall response rate (BORR)

  at 24 weeks

Secondary Outcomes (7)

• Adverse Event Summaries, Vital Signs, and Laboratory Parameters as a Measure of Safety and Tolerability

  until Week 24

• Objective response rate (ORR)

  at Weeks 12, 18, and 24

• Progression-free survival (PFS)

  for 1 year

• Durable response rate (DRR)

  for 1 year

• 1-year survival rate

  at 1 year

Study Arms (1)

HF10 plus ipilimumab

EXPERIMENTAL

Biological: HF10 plus Ipilimumab

Interventions

HF10 plus Ipilimumab BIOLOGICAL

Patients will receive the dose of 1 x 10\^7 TCID50/mL HF10 (for a total of 6 injections; the first 4 injections at 1-week intervals; the remaining 2 injections at 3-week intervals) and ipilimumab at 3 mg/kg ipilimumab (for a total of 4 intravenous infusions, each administered at 3-week intervals).

Also known as: YERVOY (for ipilimumab)

HF10 plus ipilimumab

Eligibility Criteria

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

You may qualify if:

• Patients must have Stage IIIB, IIIC or IV melanoma, which is unresectable/unresected or histologically confirmed diagnosis of metastatic malignant melanoma.
• Patients must have measurable non-visceral lesion(s) that are evaluable by the modified World Health Organization (mWHO) criteria and immune-related response criteria (irRC).
• Patients must be ≥ 18 years of age.
• Patients must have a life expectancy ≥ 24 weeks.
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• Patients must have adequate hepatic function, defined as
• Total bilirubin levels ≤ 1.5 x upper limit of normal \[ULN\] (except for patients with Gilbert's Syndrome, who must have a total bilirubin of less than 3.0 mg/dL)
• AST/ALT levels ≤ 2.5 x ULN, or ≤ 5 x ULN if liver metastases are present.
• Patients must have adequate renal function, defined as serum creatinine ≤ 1.5 x ULN or creatinine clearance (calculated) ≥ 60 mL/min/1.73 m2 for patients with creatinine \> 1.5 x ULN.
• Patients must have adequate bone marrow function, defined as
• Absolute neutrophil count ≥1,500/µL and
• Platelet count ≥ 75,000/ µL
• Patients must have no known bleeding diathesis or coagulopathy that would make intratumoral injection or biopsy unsafe.
• Patients must be ipilimumab-eligible. (This includes: 1) patients previously untreated with ipilimumab; 2) patients previously treated (more than 1 year previously) with ipilimumab using a route of administration other than intravenous infusion; and 3) patients previously treated with antitumor agents other than intravenous ipilimumab).
• Men and women of childbearing potential must agree to use adequate contraception from the time of consent through 30 days after final study treatment.

You may not qualify if:

• Patients receiving chemotherapy or radiotherapy within 4 weeks of injection of HF10, or history of Grade 4 adverse events or presence of adverse events Grade 2 or greater, except alopecia, resulting from anticancer agents administered more than 4 weeks prior to HF10 injection.
• Patients receiving anti-herpes medication within 1 week prior to initiating HF10 treatment.
• Patients with a history of significant tumor bleeding, or coagulation or bleeding disorders.
• Patients with target tumors that could potentially invade a major vascular structure (e.g., innominate artery, carotid artery), based on unequivocal imaging findings.
• Patients with Grade 2 or greater pre-existing neurologic abnormalities (CTCAE version 4.0), including Grade 2 or greater peripheral neuropathy caused by previous treatments.
• Patients with clinically evident Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), Hepatitis C virus (HCV), or Epstein-Barr virus (EBV) infection are excluded.
• Medical history of autoimmune disease (e.g., Crohn's disease, ulcerative colitis) or other diseases requiring systemic glucocorticoid or immunosuppressive therapy.
• Patients who were previously treated with ipilimumab administered by intravenous infusion.
• Concurrent use of any other investigational agents.
• Patients with active CNS metastases or carcinomatous meningitis, except patients with CNS lesions that have been treated and have no evidence of progression in the brain on CT/MRI for ≥ 3 months.
• Pregnant or breastfeeding women; women desiring to become pregnant within the timeframe of the study are also excluded.
• 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.

Sponsors & Collaborators

• Takara Bio Inc.: lead
• Theradex: collaborator

Study Sites (8)

Clinical Site

San Francisco, California, 94115, United States

Location

Clinical Site

Atlanta, Georgia, 30322, United States

Location

Clinical Site

Portland, Oregon, 97239, United States

Location

Clinical Site

Bethlehem, Pennsylvania, 18015, United States

Location

Clinical Site

Hershey, Pennsylvania, 17033, United States

Location

Clinical Site

Dallas, Texas, 75230, United States

Location

Clinical Site

Houston, Texas, 77030, United States

Location

Clinical Site

Salt Lake City, Utah, 84112, United States

Location

Related Publications (1)

• Watanabe D, Goshima F. Oncolytic Virotherapy by HSV. Adv Exp Med Biol. 2018;1045:63-84. doi: 10.1007/978-981-10-7230-7_4.

  PMID: 29896663 DERIVED

MeSH Terms

Conditions

Melanoma

Interventions

Ipilimumab

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

Study Officials

• Robert Andtbacka

  University of Utah

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: October 9, 2014
• First Posted: October 23, 2014
• Study Start: April 30, 2014
• Primary Completion: October 1, 2016
• Study Completion: August 1, 2018
• Last Updated: September 26, 2018

Record last verified: 2018-09

Locations

US (8)