MelanomaPhase 2NCT03259425
Neoadjuvant Trial of Nivolumab in Combination With HF10 Oncolytic Viral Therapy in Resectable Stage IIIB, IIIC, IVM1a Melanoma
A Phase 2 study testing Nivolumab and HF10 in people with Melanoma, run by University of Utah at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- Nivolumab and HF10
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Jan 2018to 25 Sep 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 13Show fewer
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
About this study
Official title: Phase II Neoadjuvant Trial of Nivolumab in Combination With HF10 Oncolytic Viral Therapy in Resectable Stage IIIB, IIIC, IVM1a Melanoma (Neo-NivoHF10)
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.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
Also called OPDIVO
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.
HF10Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| Nivolumab and HF10, all participants | Experimental | Not described Receives: Drug: Nivolumab; Drug: HF10 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: at time of surgery (12 weeks)
Secondary outcomes (6)
Recurrence-free Survival: Number of Participants With no Disease Recurrence After Surgery
Recurrence after surgery will be assessed by radiologic scans and confirmed by biopsy. Death within the follow-up period is also considered recurrence. This outcome will report the number of participants who were alive and who had no disease recurrence during the follow-up period.
Measured: 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
Participants were followed for survival for one year after completion of adjuvant nivolumab. Adjuvant nivolumab was planned for up to one year of adjuvant treatment after surgery. This objective reports the number of participants who were alive one year after the completion of adjuvant nivolumab.
Measured: 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
Participants were assessed radiographically and clinically prior to study start and prior to surgery. Lesions were measured, and lesions that were at least 10 mm on CT, MRI, caliper, or ruler, or at least 20 mm on x-ray were documented as Target Lesions. Lesions that did not meet criteria to be Target Lesions were documented as Non-Target lesions. Measurements of Target Lesions were summed. Change in Target Lesion measurements was used to determine response by RECIST 1.1 criteria. Complete Response (CR) indicates a disappearance of all lesions. Partial Response (PR) indicates at least 30% decrease in the sum of Target Lesions. Progressive Disease (PD) indicates at least 20% increase in the sum of Target Lesions, or the appearance of one or more new lesions after baseline. Stable Disease (SD) is neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD. Objective was reported as number of participants within each response category.
Measured: 12 weeks from baseline to surgery
Number of Participants With Complete Surgical Resection
Participants' surgical samples were assessed by a pathologist after surgery to determine if complete surgical resection was achieved after neo-adjuvant treatment with nivolumab and HF10. R0 indicates a complete surgical resection was achieved and means no residual tumor was detected after after surgery. R1 means microscopic tumor was detected and a complete surgical resection was not achieved.
Measured: Within 28 days after Day 84
Number of Participants With Adverse Events Related to HF10 Treatment
Participants were monitored for adverse events (AEs) during treatment with HF10 using CTCAE v4 criteria. AEs were graded as being mild (grade 1), moderate (grade 2), grade 3 (severe), grade 4 (life-threatening), and grade 5 (fatal). Each adverse event was reviewed by a treating investigator for relatedness to study treatment. For this outcome, the number of participants who experienced any AEs that were possible, probably, or definitely related to HF10 treatment are grouped by grade 1-2 and grade 3-5 AEs.
Measured: throughout HF10 treatment (up to 84 days)
Number of Participants With Adverse Events Related to Nivolumab Treatment
Participants were monitored for adverse events (AEs) during treatment with nivolumab using CTCAE v4 criteria. AEs were graded as being mild (grade 1), moderate (grade 2), grade 3 (severe), grade 4 (life-threatening), and grade 5 (fatal). Each adverse event was reviewed by a treating investigator for relatedness to study treatment. For this outcome, the number of participants who experienced any AEs that were possible, probably, or definitely related to nivolumab treatment are grouped by grade 1-2 and grade 3-5 AEs.
Measured: throughout nivolumab treatment (up to 84 days prior to surgery and up to 1 year after surgery)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2017
- Study start3 Jan 2018
- Primary completion21 Sep 2018
- Study completion25 Sep 2020
Why it stopped: DSMC Recommendation
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by University of UtahThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a single-arm, open label, Phase II
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb, Takara Bio Inc.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03259425
- Sponsor's protocol ID
- HCI102346
- Status last verified
- Jun 2022
- First submitted
- 18 Aug 2017
- Last updated
- 13 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Neoadjuvant Trial of Nivolumab in Combination With HF10 Oncolytic Viral Therapy in Resectable Stage IIIB, IIIC, IVM1a Melanoma (Neo-NivoHF10)
- ClinicalTrials.gov ID
- NCT03259425
- Acronym / sponsor ID
- HCI102346
- Conditions
- Melanoma
- Keywords
- Resectable Stage IIIB, IIIC, and IVM1a
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: DSMC Recommendation
- Enrolment
- 7 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb, Takara Bio Inc.
- Study start
- 3 Jan 2018 (actual)
- Primary completion
- 21 Sep 2018 (actual)
- Study completion
- 25 Sep 2020 (actual)
- First posted
- 23 Aug 2017 (actual)
- Results
- Posted 10 Oct 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a single-arm, open label, Phase II
| Arm | Type | Receives |
|---|---|---|
| Nivolumab and HF10, all participants | Experimental | Drug: Nivolumab, Drug: HF10 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NivolumabAlso: OPDIVONivolumab 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. | Drug | Nivolumab and HF10, all participants |
| HF101 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. | Drug | Nivolumab and HF10, all participants |
Primary outcome
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.
6 secondary outcomes
Recurrence-free Survival: Number of Participants With no Disease Recurrence After Surgery
Time frame: 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
Time frame: 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
Time frame: 12 weeks from baseline to surgery
Number of Participants With Complete Surgical Resection
Time frame: Within 28 days after Day 84
Number of Participants With Adverse Events Related to HF10 Treatment
Time frame: throughout HF10 treatment (up to 84 days)
Number of Participants With Adverse Events Related to Nivolumab Treatment
Time frame: throughout nivolumab treatment (up to 84 days prior to surgery and up to 1 year after surgery)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Melanoma
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 1
IL-17 Blockade to Decrease irAEs (REPLAY)
Metastatic Melanoma
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 1
A Feasibility Study Utilizing Immune Recall to Increase Response to Checkpoint Therapy
Melanoma
Active, not recruitingPhase 1/2
A Study of Dapansutrile Plus Pembrolizumab in Patients With PD-1 Refractory Advanced Melanoma
Melanoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nivolumab and HF10 in people with Melanoma, run by University of Utah at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathological Response (time frame: at time of surgery (12 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jun 2022.