PV-10 vs Chemotherapy or Oncolytic Viral Therapy for Treatment of Locally Advanced Cutaneous Melanoma

NCT02288897 | Terminated Phase 3 Results DMC

• 1 other identifier: PV-10-MM-31
• Study Type: interventional
• Target: 20
• Locations: 5 countries
• Sites: 23

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.

Conditions

Cutaneous Melanoma

Keywords

Stage III; Stage IIIB; Stage IIIC; Stage IV (M1a); Stage 3; Stage 4; IVM1a; IV(M1a); IV-M1a; in-transit; in transit; intransit; satellite; recurrent

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)

  PFS was estimated via Kaplan-Meier analysis using Response Evaluation Criteria In Solid Tumors (RECIST v1.1) criteria. Subjects who did not have an event of progression or death were censored at their last assessment date. Assessment of progression was performed by the sponsor based on review of lesion measurement and clinical progression data reported by each investigator. Events signaling progression included increase in size and/or number of study lesions, onset of visceral metastatic disease, and death. For target lesions (assigned prior to randomization), complete response (CR) required disappearance of all target lesions; partial response (PR) required \>= 30% decrease in sum of the longest diameter (SLD) of all target lesions; progressive disease (PD) required \>=20% increase in SLD of target lesions. Non-target lesions were followed for CR, PD, or non-CR/non-PD status using equivalent thresholds. Progression occurred when PD was observed in either target or non-target lesion.

  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 Outcomes (4)

• Complete Response Rate (CRR)

  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.

• Duration of Complete Response (DCR)

  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.

• Overall Survival (OS)

  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.

• Number of Participants With Adverse Events

  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.

Other Outcomes (1)

• Change in Domain Scores From Baseline Using the Patient Reported Skindex-16 Instrument

  Assessed at baseline (Day 1 at start of study treatment) and at the end of each treatment cycle (every 4 or 6 weeks) until disease progression, withdrawal of consent, or study termination; median follow-up time was 26.6 weeks, maximum was 125.8 weeks.

Study Arms (2)

PV-10

EXPERIMENTAL

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.

Drug: PV-10 (10% rose bengal disodium)

Chemotherapy or Oncolytic Viral Therapy

ACTIVE COMPARATOR

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.

Drug: Dacarbazine, temozolomide or talimogene laherparepvec

Interventions

PV-10 (10% rose bengal disodium) DRUG

PV-10

Dacarbazine, temozolomide or talimogene laherparepvec DRUG

Chemotherapy or Oncolytic Viral Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 years or older, male or female
• Histologically or cytologically confirmed melanoma
• 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)
• 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
• No lesion \> 50 mm in longest diameter; and no more than 50 lesions
• Calculated required PV-10 dose ≤ 15 mL (based on total tumor burden)
• Performance Status: Eastern Cooperative Oncology Group (ECOG) 0-2
• 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)
• 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)
• 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)

You may not qualify if:

• Presence or history of visceral melanoma metastasis
• Presence of active nodal metastases (e.g., radiologic or clinical evidence of current nodal disease)
• Presence of more than 50 melanoma lesions
• Radiation therapy to any Study Lesion within 6 weeks of initial study treatment.
• 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
• Immunotherapy for cancer within 4 weeks of initial study treatment
• Local treatment (e.g., surgery, cryotherapy, laser ablation) to any Study Lesion within 4 weeks of initial study treatment
• Anti-tumor vaccine therapy within 6 weeks of initial study treatment.
• Investigational agents within 4 weeks of initial study treatment.
• 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

Sponsors & Collaborators

• Provectus Biopharmaceuticals, Inc.: lead

Study Sites (23)

Sharp Memorial Hospital - Clinical Oncology Research

San Diego, California, 92123, United States

Location

Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida, 33140, United States

Location

Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Washington University School of Medicine - Dermatology

St Louis, Missouri, 63110, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Atlantic Health System

Morristown, New Jersey, 07960, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

Location

Oklahoma Cancer Specialists and Research Institute

Tulsa, Oklahoma, 74146, United States

Location

St Luke's University Hospital and Health Network

Easton, Pennsylvania, 18045, United States

Location

Penn State Hershey Cancer Institute

Hershey, Pennsylvania, 17033, United States

Location

M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Unité Cancéro-Dermatologie, Hôtel-Dieu CHU Nantes

Nantes, France

Location

Institut Claudius Regaud, IUCT ONCOPOLE

Toulouse, 31059, France

Location

Klinik für Dermatologie, Venerologie und Allergologie Charite Universitätsmedizin Berlin

Berlin, Germany

Location

Klinik für Dermatologie Universitätsklinikum Essen Studienzentrum

Essen, Germany

Location

Klinik für Dermatologie, Venerologie und Allergologie Universitätsklinikum Schleswig-Holstein Hautkrebszentrum

Kiel, Germany

Location

Hautklinik Klinikum der Johannes Gutenberg Universität Hautkrebszentrum

Mainz, Germany

Location

IRCCS Instituto Nazionale Tumori "Fondazione Giovanni Pascale"

Napoli, Italy

Location

Istituto Dermopatico dell'Immacolata (IDI IRCCS)

Rome, Italy

Location

Azienda Sanitaria Azienda Ospedaliera Universitaria Senese

Siena, Italy

Location

Centro de Estudios y Prevención del Cancer A.C.

Juchitán de Zaragoza, Oaxaca, 70000, Mexico

Location

Neurociencias Estudios Clínicos S.C.

Culiacán, Sinaloa, 80020, Mexico

Location

MeSH Terms

Conditions

Melanoma; Recurrence

Interventions

Rose Bengal; Dacarbazine; Temozolomide; talimogene laherparepvec

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Fluoresceins; Spiro Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Xanthenes; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Polycyclic Compounds; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

Planned accrual was 225 subjects. However, due to slow accrual during a period of rapid change in global drug development for cutaneous melanoma, the study was terminated early after 20 subjects initiated study treatment. Because the study was terminated prior to achievement of pre-specified efficacy thresholds, the planned central independent review was not conducted and the small number of subjects precluded formal analysis and scientifically meaningful interpretation of efficacy parameters.

Results Point of Contact

• Title: Eric Wachter, Chief Technology Officer
• Organization: Provectus Biopharmaceuticals, Inc.

wachter@pvct.com

865-769-4011

Study Officials

• Eric Wachter, Ph.D.

  Provectus Biopharmaceuticals, Inc.

  STUDY DIRECTOR

• Sanjiv Agarwala, M.D.

  St Luke's University Hospital and Health Network

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Blinded review by independent review committee (IRC) for primary and key secondary endpoints.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2014
• First Posted: November 11, 2014
• Study Start: April 1, 2015
• Primary Completion: April 1, 2019
• Study Completion: September 1, 2019
• Last Updated: January 19, 2022
• Results First Posted: January 19, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2); IT (3); ME (2); US (12); DE (4)