Description:
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.
Title
- Brief Title: Neoadjuvant Trial of Nivolumab in Combination With HF10 Oncolytic Viral Therapy in Resectable Stage IIIB, IIIC, IVM1a Melanoma
- Official Title: Phase II Neoadjuvant Trial of Nivolumab in Combination With HF10 Oncolytic Viral Therapy in Resectable Stage IIIB, IIIC, IVM1a Melanoma (Neo-NivoHF10)
Clinical Trial IDs
- ORG STUDY ID:
HCI102346
- NCT ID:
NCT03259425
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Nivolumab | OPDIVO | Nivolumab and HF10, all patients |
HF10 | | Nivolumab and HF10, all patients |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Nivolumab and HF10, all patients | Experimental | | |
Eligibility Criteria
Inclusion Criteria:
- Patients must be >18 years or older.
- Patients 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.
- Patients 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.
- Patients 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.
- Patients 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.
- Patients must be able to provide informed consent and willing to sign an approved
consent form that conforms to federal and institutional guidelines.
Exclusion Criteria:
- Patients with active visceral, central nervous system, or any bone metastases melanoma
(Stage IVM1b or IVM1c).
- Patients whose primary diagnosis was ocular melanoma.
- Patients receiving anti-herpes medication (i.e., acyclovir, famciclovir, or
valacyclovir) within 1 week prior to initiating HF10 treatment. Patients may not
require intermittent or chronic systemic (intravenous or oral) treatment with an
antiherpetic drug other than intermittent topical use.
- Patients 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.
- Patients 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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Pathological Response |
Time Frame: | 12 weeks |
Safety Issue: | |
Description: | Following 12 weeks of neoadjuvant treatment with nivolumab and HF10, patients 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 Outcome Measures
Measure: | Recurrence-free Survival |
Time Frame: | 1 year post surgery |
Safety Issue: | |
Description: | Recurrence after surgery will be assessed by radiologic scans scheduled per section 8 and confirmed by biopsy. |
Measure: | Overall Survival |
Time Frame: | 2 years (1 year after stopping 1 year of Nivolumab) |
Safety Issue: | |
Description: | patients will be followed for survival for one year after completion of adjuvant nivolumab |
Measure: | Complete Surgical Resection |
Time Frame: | Within 28 days after Day 84 |
Safety Issue: | |
Description: | patients will be assessed at surgery to determine if complete surgical resection was achievable after neo-adjuvant treatment with nivolumab and HF10. |
Measure: | Rate of Adverse Events for Patients While Taking Nivolumab and HF10 |
Time Frame: | Patient safety will be evaluated throughout the treatment period and follow up (Treatment with HF10 is expected to last for 84 days, treatment with nivolumab is expected to last 1 year for each patient after surgery and follow up for 1 year |
Safety Issue: | |
Description: | patients will be monitored for adverse events related to nivolumab and HF10 using CTCAE criteria |
Measure: | Radiographic Response Per RECIST 1.1 |
Time Frame: | 12 weeks from baseline to surgery |
Safety Issue: | |
Description: | Patients will be assessed radiographically with CT or MRI scan or assessed clinically. |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Terminated |
Lead Sponsor: | University of Utah |
Trial Keywords
- Resectable Stage IIIB, IIIC, and IVM1a
Last Updated
November 3, 2020