MelanomaPhase 1/2NCT02557321
PV-10 in Combination With Pembrolizumab for Treatment of Metastatic Melanoma
A Phase 1/2 study testing PV-10 and Pembrolizumab in people with Melanoma, run by Provectus Biopharmaceuticals, Inc. at 5 sites in United States.
Trial summary
This is an international multicenter, open-label, sequential phase study of intralesional (IL) PV-10 in combination with immune checkpoint inhibition. Metastatic melanoma patients (Stage IV or Stage III unresectable, in-transit or satellite disease) with at least one injectable lesion who are candidates for… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- PV-10 and Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 5 sitesUnited States
- Study dates
- Oct 2015to Apr 2025
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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
- Age 18 years or older, male or female.
- Histologically or cytologically confirmed diagnosis of melanoma.
- Stage IV or Stage III (unresectable, in-transit or satellite) melanoma.
- At least 1 Injectable Lesion (i.e., cutaneous, subcutaneous, soft tissue, superficial nodal or palpable nodal lesion with longest diameter at least 5 mm that is suitable for injection with PV-10).
- A minimum of 1 measurable Target Lesion that can be accurately measured by calipers, computed tomography (CT) or magnetic resonance imaging (MRI) consisting of at least one of the following:
- at least one cutaneous lesion (each lesion ≥ 10 mm longest diameteror up to 5 lesions in aggregate having a sum of longest diameters ≥ 10 mm); and/or
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- at least one subcutaneous or soft tissue lesion (each lesion ≥ 10 mm in longest diameter by CT or MRI); and/or
- at least one nodal lesion (each lesion ≥ 15 mm in short axis diameter by CT or MRI); and/or
- at least one visceral lesion (each lesion ≥ 10 mm in longest diameter by CT or MRI).
- Performance Status: Eastern Cooperative Oncology Group (ECOG) 0-1.
- Clinical Laboratories:
- absolute neutrophil count (ANC) ≥ 1.5 x 109/L and platelet count ≥100 x 109/L
- estimated creatinine clearance (CrCl, by Cockcroft-Gault formula) or estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2
- total bilirubin ≤ 3 times the upper limit of normal (ULN)
- aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) ≤ 5 times the upper limit of normal (ULN)
- Thyroid function abnormality ≤ Common Toxicity Criteria for Adverse Effects (CTCAE) Grade 2.
Who cannot join
- Untreated or clinically active melanoma brain metastases.
- Subjects with ≤ 3 brain metastases and each ≤ 1 cm size that were treated with either surgical resection and/or radiation therapy are eligible for study participation provided (a) there is no evidence of progressive central nervous system (CNS) disease on brain imaging at least 30 days after definitive treatment and (b) the subject is not taking prednisone at >10 mg or equivalent daily.
- Subjects with > 1 cm or > 3 in number treated brain metastases are eligible for study participation provided (a) there is no evidence of progressive CNS disease on brain imaging at least 90 days after treatment with surgery and/or radiation therapy and (b) if the subject is not taking prednisone at >10 mg or equivalent daily.
- Prior treatment with PV-10 or any checkpoint inhibitor; however, subjects (a) who have failed to achieve a complete or partial response within 24 weeks following initiation of checkpoint inhibition or (b) who progressed after more than 12 weeks of checkpoint inhibition are eligible for study participation in the Phase 1b Expansion Cohort 1 without washout period for checkpoint inhibition.
- Other prior cancer therapy or anti-cancer vaccine within the lesser of 4 weeks or 5 half-lives before initial study treatment.
- Known sensitivity to any of the products or components to be administered during dosing.
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- Concurrent or Intercurrent Illness:
- History or evidence of symptomatic autoimmune pneumonitis, glomerulonephritis, vasculitis, or other systemic autoimmune disease.
- Evidence of clinically significant immunosuppression.
- Impaired wound healing or other extremity complications due to severe or uncontrolled diabetes mellitus in subjects whose Injectable Lesions are located in an extremity.
- Severe peripheral vascular disease (i.e., severe claudication [pain occurring after less than 200 meters of walking], rest pain, ischemic ulceration or gangrene) in subjects whose Injectable Lesions are located in an extremity.
- Significant concurrent or intercurrent illness, psychiatric disorders, or alcohol or chemical dependence that would, in the opinion of the Investigator, compromise the subject's safety or compliance or interfere with interpretation of study results.
- Uncontrolled thyroid disease or cystic fibrosis.
- Clinically significant acute or unstable cardiovascular, cerebrovascular (stroke), renal, gastrointestinal, pulmonary, immunological, endocrine, or central nervous system disorders.
- Malignancy other than melanoma within 2 years of enrollment except for: adequately treated (i.e., with curative intent) basal or squamous cell carcinoma, in situ carcinoma of the cervix, in situ ductal adenocarcinoma of the breast, in situ prostate cancer, or limited stage bladder cancer.
- Pregnancy:
- Female subjects who are pregnant or lactating.
- Female subjects who have positive serum pregnancy test taken within 14 days of initiation of study treatment.
- Female subjects of childbearing potential (defined as having a menstrual cycle within the past 12 months and not having had a surgical procedure to accomplish sterilization) who are not using highly effective contraception (e.g., oral contraceptives, intrauterine devices, double barrier methods such as condoms and diaphragms, abstinence or equivalent measures).
- Male subjects who are unwilling to use acceptable method of effective contraception.
- Subjects unable to comprehend and give informed consent are excluded.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
St Luke's University Health Network
Easton, Pennsylvania, 18045
MD Anderson Cancer Center
Houston, Texas, 77230
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03756
Oregon Health & Science University
Portland, Oregon, 97239
Moffitt Cancer Center
Tampa, Florida, 33612
About this study
Official title: A Phase 1b/2 Study of PV-10 Intralesional Injection in Combination With Systemic Immune Checkpoint Inhibition for Treatment of Metastatic Melanoma
This is an international multicenter, open-label, sequential phase study of intralesional (IL) PV-10 in combination with immune checkpoint inhibition. Metastatic melanoma patients (Stage IV or Stage III unresectable, in-transit or satellite disease) with at least one injectable lesion who are candidates for pembrolizumab (both treatment naïve patients and treatment refractory patients who have failed to achieve a complete or partial response to or previously progressed on one or more checkpoint inhibitor) will be eligible for study participation. In the Phase 1b portion of the study, all participants will receive the combination of IL PV-10 and pembrolizumab (i.e., PV-10 + standard of care). In the subsequent Phase 2 portion of the study participants will be randomized 1:1 to receive either the combination of IL PV-10 and pembrolizumab or pembrolizumab alone (i.e., PV-10 + standard of care vs. standard of care).
Read the detailed description
Phase 1b. Up to 24 eligible subjects will be enrolled in an initial cohort in the Phase 1b portion of the study (Main Cohort). Up to an additional 24 eligible subjects who have failed to achieve a complete or partial response to or progressed on prior checkpoint inhibition will be enrolled in a first expansion cohort (Expansion Cohort 1). Up to an additional 24 eligible subjects with Stage III unresectable, in-transit or satellite melanoma will be enrolled in a second expansion cohort (Expansion Cohort 2). Each subject in each Phase 1b cohort will receive the combination of IL PV-10 and pembrolizumab.
Phase 2. A total of an estimated 120 eligible subjects will be randomized in a 1:1 ratio to the two treatment arms (i.e., PV-10 + pembrolizumab or pembrolizumab alone) in the Phase 2 portion of the study. This number of subjects may be modified based on emerging evidence of preliminary efficacy and effect size from the Phase 1b and initial Phase 2 portions of the study.
Subjects assigned to receive PV-10 in Phase 1b and 2 will receive initial IL PV-10 to their injectable lesions commencing on study Day 1 for up to 12 weeks (i.e., investigational Treatment Phase of the study). PV-10 may be re-administered at 21-day (3-week) intervals during the Treatment Phase of the study to any remaining, uninjected injectable lesions until all injectable lesions have been injected. Lesions that fail to exhibit complete ablation may be re-injected on this schedule.
Pembrolizumab will be administered at 21-day (3-week) intervals per prescribing information (label) commencing on study Day 1 for up to 24 months or until disease progression, toxicity requiring discontinuation of study treatment or study termination.
- Conditions
- Melanoma
- Being tested
- PV-10, Pembrolizumab
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PV-10Drug
Also called Rose Bengal Disodium
PV-10 will be administered by intralesional injection every 3 weeks at Day 1 (Week 1), Week 4, Week 7, Week 10 and Week 13
PembrolizumabDrug
Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1)
| Study group | Role | What they receive |
|---|---|---|
| Phase 1b | Experimental | PV-10 (intralesional) and pembrolizumab (2 mg/kg every 3 weeks) Receives: Drug: PV-10; Drug: Pembrolizumab |
| Phase 2 (Arm 1) | Experimental | PV-10 (intralesional) and pembrolizumab (2 mg/kg every 3 weeks) Receives: Drug: PV-10; Drug: Pembrolizumab |
| Phase 2 (Arm 2) | Active comparator | Pembrolizumab (2 mg/kg every 3 weeks) Receives: Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of the combination regimen assessed by adverse events (AEs)
Phase 1b: Safety and tolerability of the combination regimen will be assessed by monitoring the frequency, duration, severity and attribution of adverse events (AEs) and toxicities requiring discontinuation of study treatment, and evaluating changes in laboratory values and vital signs
Measured: Start of treatment until 4 weeks after final administration of PV-10
Progression Free Survival (PFS)
Phase 2: Response evaluated by blinded independent review committee assessment per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1
Measured: Up to 24 months from initiation of study treatment
Secondary outcomes (5)
Progression Free Survival (PFS)
Phase 1b: Response evaluated per RECIST 1.1
Measured: Up to 24 months from initiation of study treatment
Objective Response Rate (ORR)
Phase 1b and 2: Response evaluated per RECIST 1.1
Measured: Up to 24 months from initiation of study treatment
Change in immune biomarkers
Phase 1b: Peripheral Blood Mononuclear Cells (PBMCs) assessed vs. baseline values for changes in T cell populations
Measured: Up to 28 weeks from initiation of study treatment
Overall Survival (OS)
Phase 1b and 2
Measured: 24 months from initiation of study treatment for last subject randomized
Safety and tolerability of the combination regimen assessed by adverse events (AEs)
Phase 2: Safety and tolerability of the combination regimen will be assessed by monitoring the frequency, duration, severity and attribution of adverse events (AEs) and toxicities requiring discontinuation of study treatment, and evaluating changes in laboratory values and vital signs
Measured: Start of treatment until 4 weeks after final administration of PV-10
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2015 (estimated)
- Study startOct 2015
- Primary completionMay 2023
- Study completionApr 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MelanomaStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Provectus Biopharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Eric Wachter, Ph.D., Study director, Provectus Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02557321
- Sponsor's protocol ID
- PV-10-MM-1201
- Status last verified
- Nov 2023
- First submitted
- 20 Sep 2015
- Last updated
- 21 Nov 2023
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b/2 Study of PV-10 Intralesional Injection in Combination With Systemic Immune Checkpoint Inhibition for Treatment of Metastatic Melanoma
- ClinicalTrials.gov ID
- NCT02557321
- Acronym / sponsor ID
- PV-10-MM-1201
- Conditions
- Melanoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Provectus Biopharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Oct 2015 (actual)
- Primary completion
- May 2023 (actual)
- Study completion
- Apr 2025 (estimated)
- First posted
- 23 Sep 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an international multicenter, open-label, sequential phase study of intralesional (IL) PV-10 in combination with immune checkpoint inhibition. Metastatic melanoma patients (Stage IV or Stage III unresectable, in-transit or satellite disease) with at least one injectable lesion who are candidates for pembrolizumab (both treatment naïve patients and treatment refractory patients who have failed to achieve a complete or partial response to or previously progressed on one or more checkpoint inhibitor) will be eligible for study participation. In the Phase 1b portion of the study, all participants will receive the combination of IL PV-10 and pembrolizumab (i.e., PV-10 + standard of care). In the subsequent Phase 2 portion of the study participants will be randomized 1:1 to receive either the combination of IL PV-10 and pembrolizumab or pembrolizumab alone (i.e., PV-10 + standard of care vs. standard of care).
Detailed description
Phase 1b. Up to 24 eligible subjects will be enrolled in an initial cohort in the Phase 1b portion of the study (Main Cohort). Up to an additional 24 eligible subjects who have failed to achieve a complete or partial response to or progressed on prior checkpoint inhibition will be enrolled in a first expansion cohort (Expansion Cohort 1). Up to an additional 24 eligible subjects with Stage III unresectable, in-transit or satellite melanoma will be enrolled in a second expansion cohort (Expansion Cohort 2). Each subject in each Phase 1b cohort will receive the combination of IL PV-10 and pembrolizumab.
Phase 2. A total of an estimated 120 eligible subjects will be randomized in a 1:1 ratio to the two treatment arms (i.e., PV-10 + pembrolizumab or pembrolizumab alone) in the Phase 2 portion of the study. This number of subjects may be modified based on emerging evidence of preliminary efficacy and effect size from the Phase 1b and initial Phase 2 portions of the study.
Subjects assigned to receive PV-10 in Phase 1b and 2 will receive initial IL PV-10 to their injectable lesions commencing on study Day 1 for up to 12 weeks (i.e., investigational Treatment Phase of the study). PV-10 may be re-administered at 21-day (3-week) intervals during the Treatment Phase of the study to any remaining, uninjected injectable lesions until all injectable lesions have been injected. Lesions that fail to exhibit complete ablation may be re-injected on this schedule.
Pembrolizumab will be administered at 21-day (3-week) intervals per prescribing information (label) commencing on study Day 1 for up to 24 months or until disease progression, toxicity requiring discontinuation of study treatment or study termination.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Phase 1b | Experimental | Drug: PV-10, Drug: PembrolizumabPV-10 (intralesional) and pembrolizumab (2 mg/kg every 3 weeks) |
| Phase 2 (Arm 1) | Experimental | Drug: PV-10, Drug: PembrolizumabPV-10 (intralesional) and pembrolizumab (2 mg/kg every 3 weeks) |
| Phase 2 (Arm 2) | Active comparator | Drug: PembrolizumabPembrolizumab (2 mg/kg every 3 weeks) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Age 18 years or older, male or female.
- Histologically or cytologically confirmed diagnosis of melanoma.
- Stage IV or Stage III (unresectable, in-transit or satellite) melanoma.
- At least 1 Injectable Lesion (i.e., cutaneous, subcutaneous, soft tissue, superficial nodal or palpable nodal lesion with longest diameter at least 5 mm that is suitable for injection with PV-10).
- A minimum of 1 measurable Target Lesion that can be accurately measured by calipers, computed tomography (CT) or magnetic resonance imaging (MRI) consisting of at least one of the following:
Key exclusion criteria (21 listed)
- Untreated or clinically active melanoma brain metastases.
- Prior treatment with PV-10 or any checkpoint inhibitor; however, subjects (a) who have failed to achieve a complete or partial response within 24 weeks following initiation of checkpoint inhibition or (b) who progressed after more than 12 weeks of checkpoint inhibition are eligible for study participation in the Phase 1b Expansion Cohort 1 without washout period for checkpoint inhibition.
- Other prior cancer therapy or anti-cancer vaccine within the lesser of 4 weeks or 5 half-lives before initial study treatment.
- Known sensitivity to any of the products or components to be administered during dosing.
- Concurrent or Intercurrent Illness:
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 |
|---|---|---|
| PV-10Also: Rose Bengal DisodiumPV-10 will be administered by intralesional injection every 3 weeks at Day 1 (Week 1), Week 4, Week 7, Week 10 and Week 13 | Drug | Phase 1b, Phase 2 (Arm 1) |
| PembrolizumabPembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1) | Drug | Phase 1b, Phase 2 (Arm 1), Phase 2 (Arm 2) |
Primary outcome
Safety and tolerability of the combination regimen assessed by adverse events (AEs)
Time frame: Start of treatment until 4 weeks after final administration of PV-10
Phase 1b: Safety and tolerability of the combination regimen will be assessed by monitoring the frequency, duration, severity and attribution of adverse events (AEs) and toxicities requiring discontinuation of study treatment, and evaluating changes in laboratory values and vital signs
Progression Free Survival (PFS)
Time frame: Up to 24 months from initiation of study treatment
Phase 2: Response evaluated by blinded independent review committee assessment per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1
5 secondary outcomes
Progression Free Survival (PFS)
Time frame: Up to 24 months from initiation of study treatment
Objective Response Rate (ORR)
Time frame: Up to 24 months from initiation of study treatment
Change in immune biomarkers
Time frame: Up to 28 weeks from initiation of study treatment
Overall Survival (OS)
Time frame: 24 months from initiation of study treatment for last subject randomized
Safety and tolerability of the combination regimen assessed by adverse events (AEs)
Time frame: Start of treatment until 4 weeks after final administration of PV-10
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Nov 2023.
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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.
Eric Wachter, Ph.D. study director
Provectus Pharmaceuticals, Inc.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing PV-10 and Pembrolizumab in people with Melanoma, run by Provectus Biopharmaceuticals, Inc. at 5 sites 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 16 inclusion and 21 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: status not confirmed, as of the sponsor's last update on 21 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Results are not available in the source record.
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?
Safety and tolerability of the combination regimen assessed by adverse events (AEs) (time frame: Start of treatment until 4 weeks after final administration of PV-10). The study lists 2 primary outcomes in all. 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 21 Nov 2023.