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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02557321




Registration number
NCT02557321
Ethics application status
Date submitted
20/09/2015
Date registered
23/09/2015
Date last updated
5/03/2020

Titles & IDs
Public title
PV-10 in Combination With Pembrolizumab for Treatment of Metastatic Melanoma
Scientific title
A Phase 1b/2 Study of PV-10 Intralesional Injection in Combination With Systemic Immune Checkpoint Inhibition for Treatment of Metastatic Melanoma
Secondary ID [1] 0 0
PV-10-MM-1201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - PV-10
Treatment: Drugs - Pembrolizumab

Experimental: Phase 1b - PV-10 (intralesional) and pembrolizumab (2 mg/kg every 3 weeks)

Experimental: Phase 2 (Arm 1) - PV-10 (intralesional) and pembrolizumab (2 mg/kg every 3 weeks)

Active Comparator: Phase 2 (Arm 2) - Pembrolizumab (2 mg/kg every 3 weeks)


Treatment: Drugs: PV-10
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

Treatment: Drugs: Pembrolizumab
Pembrolizumab will be administered intravenously every 3 weeks starting at Day 1 (Week 1)

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
Start of treatment until 4 weeks after final administration of PV-10
Primary outcome [2] 0 0
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
Timepoint [2] 0 0
Up to 24 months from initiation of study treatment
Secondary outcome [1] 0 0
Progression Free Survival (PFS) - Phase 1b: Response evaluated per RECIST 1.1
Timepoint [1] 0 0
Up to 24 months from initiation of study treatment
Secondary outcome [2] 0 0
Objective Response Rate (ORR) - Phase 1b and 2: Response evaluated per RECIST 1.1
Timepoint [2] 0 0
Up to 24 months from initiation of study treatment
Secondary outcome [3] 0 0
Change in immune biomarkers - Phase 1b: Peripheral Blood Mononuclear Cells (PBMCs) assessed vs. baseline values for changes in T cell populations
Timepoint [3] 0 0
Up to 28 weeks from initiation of study treatment
Secondary outcome [4] 0 0
Overall Survival (OS) - Phase 1b and 2
Timepoint [4] 0 0
24 months from initiation of study treatment for last subject randomized
Secondary outcome [5] 0 0
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
Timepoint [5] 0 0
Start of treatment until 4 weeks after final administration of PV-10

Eligibility
Key inclusion criteria
1. Age 18 years or older, male or female.

2. Histologically or cytologically confirmed diagnosis of melanoma.

3. Stage IV or Stage III (unresectable, in-transit or satellite) melanoma.

4. 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).

5. 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

- 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).

6. Performance Status: Eastern Cooperative Oncology Group (ECOG) 0-1.

7. 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)

8. Thyroid function abnormality = Common Toxicity Criteria for Adverse Effects (CTCAE)
Grade 2.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. 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.

2. 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.

3. Other prior cancer therapy or anti-cancer vaccine within the lesser of 4 weeks or 5
half-lives before initial study treatment.

4. Known sensitivity to any of the products or components to be administered during
dosing.

5. 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.

6. 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.

7. Subjects unable to comprehend and give informed consent are excluded.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1/Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Princess Alexandra Hospital - Brisbane
Recruitment postcode(s) [1] 0 0
4102 - Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
New Hampshire
Country [4] 0 0
United States of America
State/province [4] 0 0
Oregon
Country [5] 0 0
United States of America
State/province [5] 0 0
Pennsylvania
Country [6] 0 0
United States of America
State/province [6] 0 0
Texas

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Provectus Biopharmaceuticals, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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 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).
Trial website
https://clinicaltrials.gov/show/NCT02557321
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Eric Wachter, Ph.D.
Address 0 0
Provectus Pharmaceuticals, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Eric Wachter, Ph.D.
Address 0 0
Country 0 0
Phone 0 0
865-769-4011
Fax 0 0
Email 0 0
wachter@pvct.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02557321