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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02288897




Registration number
NCT02288897
Ethics application status
Date submitted
4/11/2014
Date registered
11/11/2014
Date last updated
19/01/2022

Titles & IDs
Public title
PV-10 vs Chemotherapy or Oncolytic Viral Therapy for Treatment of Locally Advanced Cutaneous Melanoma
Scientific title
PV-10 Intralesional Injection vs Systemic Chemotherapy or Oncolytic Viral Therapy for Treatment of Locally Advanced Cutaneous Melanoma
Secondary ID [1] 0 0
PV-10-MM-31
Universal Trial Number (UTN)
Trial acronym
Linked study record

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

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - PV-10 (10% rose bengal disodium)
Treatment: Drugs - Dacarbazine, temozolomide or talimogene laherparepvec

Experimental: PV-10 - Subjects will receive intralesional PV-10 to all Study Lesions on study Day 1. PV-10 should be re-administered at 28-day intervals until complete response, disease progression or study termination occurs.

Active Comparator: Chemotherapy or Oncolytic Viral Therapy - Subjects will receive (a) dacarbazine (intravenously at 850 m/m2) or temozolomide (orally at 200 mg/m2 daily for 5 consecutive days), administered at consecutive 28-day intervals, or (b) intralesional talimogene laherparepvec administered on an initial 21 interval followed by consecutive 14 day intervals, until complete response, disease progression or study termination occurs.


Treatment: Drugs: PV-10 (10% rose bengal disodium)


Treatment: Drugs: Dacarbazine, temozolomide or talimogene laherparepvec
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS)
Timepoint [1] 0 0
Assessed every 12 weeks until disease progression, withdrawal of consent, or study termination; progression detected between formal assessments was documented at the time of detection; median follow-up time for PFS was 26.6 weeks, maximum was 125.8 weeks.
Secondary outcome [1] 0 0
Complete Response Rate (CRR)
Timepoint [1] 0 0
Assessed every 12 weeks until disease progression, withdrawal of consent, or study termination; median follow-up time for CRR was 26.6 weeks, maximum was 125.8 weeks.
Secondary outcome [2] 0 0
Duration of Complete Response (DCR)
Timepoint [2] 0 0
Assessed every 12 weeks until disease progression, withdrawal of consent, or study termination; median follow-up time for DCR was 26.7 weeks, maximum was 77.7 weeks.
Secondary outcome [3] 0 0
Overall Survival (OS)
Timepoint [3] 0 0
Assessed every 12 weeks upon withdrawal from active study participation until death, withdrawal of consent, or study termination; median follow-up time for survival was 82.4 weeks, maximum was 167.0 weeks.
Secondary outcome [4] 0 0
Number of Participants With Adverse Events
Timepoint [4] 0 0
Assessed every 4 weeks until 28 days after last treatment; median duration of treatment was 11.8 and 9.5 weeks in each treatment group, respectively.

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

2. Histologically or cytologically confirmed melanoma

3. Recurrent, satellite or in-transit locally advanced cutaneous or subcutaneous melanoma
metastases (i.e., American Joint Committee on Cancer (AJCC) Stage IIIB, IIIC or Stage
IV M1a with no active nodal metastases)

4. At least 1 measurable Target Lesion that can be accurately measured by calipers or
computed tomography (CT) consisting of:

- at least one cutaneous lesion (each lesion = 10 mm in longest diameter or up to 5
lesions having a sum of longest diameters = 10 mm); and/or

- at least one subcutaneous lesion (each lesion = 10 mm in longest diameter by CT);

- where Target Lesions should be at least 10 mm from any other lesion

5. No lesion > 50 mm in longest diameter; and no more than 50 lesions

6. Calculated required PV-10 dose = 15 mL (based on total tumor burden)

7. Performance Status: Eastern Cooperative Oncology Group (ECOG) 0-2

8. Not a candidate for treatment with an immune checkpoint inhibitor (e.g., failed or did
not tolerate prior therapy, or due to co-morbidities, pre-existing autoimmune disease,
drug unavailability or standard of care)

9. Not a candidate for targeted therapy with BRAF or combined BRAF/MEK inhibitors (e.g.,
failed or did not tolerate prior therapy, BRAF V600 wild-type or due to drug
unavailability or standard of care)

10. Clinical Laboratories:

- Absolute neutrophil count (ANC) = 1.5 x 10^9/L and platelet count =100 x 10^9/L

- Creatinine = 3 times the upper limit of normal (ULN)

- Estimated creatinine clearance (CrCl) 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)

- Lactate dehydrogenase (LDH) = 2 times the upper limit of normal (ULN).

11. Thyroid function abnormality = Grade 2

12. Candidate for at least one comparator drug:

- Subjects must be candidates for at least one of the designated comparator drugs
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Presence or history of visceral melanoma metastasis

2. Presence of active nodal metastases (e.g., radiologic or clinical evidence of current
nodal disease)

3. Presence of more than 50 melanoma lesions

4. Radiation therapy to any Study Lesion within 6 weeks of initial study treatment.

5. Chemotherapy or other systemic cancer therapy within 4 weeks of initial study
treatment (6 weeks for nitrosoureas or mitomycin), or regional chemotherapy (limb
infusion or perfusion) within 12 weeks of initial study treatment

6. Immunotherapy for cancer within 4 weeks of initial study treatment

7. Local treatment (e.g., surgery, cryotherapy, laser ablation) to any Study Lesion
within 4 weeks of initial study treatment

8. Anti-tumor vaccine therapy within 6 weeks of initial study treatment.

9. Investigational agents within 4 weeks of initial study treatment.

10. Concurrent or Intercurrent Illness:

- Impaired wound healing or other extremity complications due to diabetes mellitus
in subjects whose Study Lesions are located in an extremity

- Severe peripheral vascular disease in subjects whose Study 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

11. Pregnancy:

- Female subjects who are pregnant or lactating

- Female subjects who have positive serum pregnancy test taken within 14 days of
study treatment

- Female subjects of child-bearing potential who are unwilling to use highly
effective contraception (e.g., combined (estrogen and progestogen containing) or
progestogen-only hormonal contraceptives, intrauterine devices, bilateral tubal
ligation, vasectomized partner, sexual abstinence or equivalent measures) for the
duration of study treatment

12. Contraindication for all comparators:

- Subjects with contraindications to all of the designated comparator drugs

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
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/04/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/09/2019
Sample size
Target
Accrual to date
Final
20
Recruitment in Australia
Recruitment state(s)
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
Missouri
Country [4] 0 0
United States of America
State/province [4] 0 0
New Hampshire
Country [5] 0 0
United States of America
State/province [5] 0 0
New Jersey
Country [6] 0 0
United States of America
State/province [6] 0 0
North Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Oklahoma
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
United States of America
State/province [10] 0 0
Utah
Country [11] 0 0
France
State/province [11] 0 0
Nantes
Country [12] 0 0
France
State/province [12] 0 0
Toulouse
Country [13] 0 0
Germany
State/province [13] 0 0
Berlin
Country [14] 0 0
Germany
State/province [14] 0 0
Essen
Country [15] 0 0
Germany
State/province [15] 0 0
Kiel
Country [16] 0 0
Germany
State/province [16] 0 0
Mainz
Country [17] 0 0
Italy
State/province [17] 0 0
Napoli
Country [18] 0 0
Italy
State/province [18] 0 0
Rome
Country [19] 0 0
Italy
State/province [19] 0 0
Siena
Country [20] 0 0
Mexico
State/province [20] 0 0
Oaxaca
Country [21] 0 0
Mexico
State/province [21] 0 0
Sinaloa

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, randomized controlled trial (RCT) of
single-agent intralesional PV-10 versus systemic chemotherapy or intralesional oncolytic
viral therapy to assess treatment of locally advanced cutaneous melanoma in patients who (1)
are not candidates for targeted therapy and (2) are not candidates for an immune checkpoint
inhibitor. Subjects in the comparator arm will receive the Investigator's choice of
dacarbazine (DTIC), temozolomide (TMZ) or intralesional talimogene laherparepvec as
determined by Investigator preference and standard of care in the Investigator's country or
region. Effectiveness will be assessed by comparison of progression-free survival (PFS)
between all intent-to-treat (ITT) subjects in the two study treatment arms.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02288897
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Eric Wachter, Ph.D.
Address 0 0
Provectus Biopharmaceuticals, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT02288897