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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2017 by Provectus Pharmaceuticals
Sponsor:
Information provided by (Responsible Party):
Provectus Pharmaceuticals ( Provectus Biopharmaceuticals, Inc. )
ClinicalTrials.gov Identifier:
NCT02288897
First received: November 4, 2014
Last updated: April 18, 2017
Last verified: April 2017
  Purpose
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) have failed or are not otherwise candidates for targeted therapy and (2) have failed or are not otherwise candidates for at least one 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.

Condition Intervention Phase
Melanoma Recurrent
Drug: PV-10 (10% rose bengal disodium)
Drug: Dacarbazine, temozolomide or talimogene laherparepvec
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: PV-10 Intralesional Injection vs Systemic Chemotherapy or Oncolytic Viral Therapy for Treatment of Locally Advanced Cutaneous Melanoma

Resource links provided by NLM:


Further study details as provided by Provectus Pharmaceuticals:

Primary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: Assessed every 12 weeks up to 18 months ]

Secondary Outcome Measures:
  • Complete response rate (CRR) [ Time Frame: Assessed every 12 weeks up to 18 months ]
  • Duration of complete response [ Time Frame: Assessed every 12 weeks up to 18 months ]
  • Overall survival (OS) [ Time Frame: Assessed every 12 weeks up to 18 months ]
  • Number of participants with adverse events [ Time Frame: Assessed every 4 weeks until 28 days after last treatment ]
    Safety and tolerability will be assessed by monitoring the frequency, duration, severity and attribution of adverse events and evaluating changes in laboratory values and vital signs.


Other Outcome Measures:
  • Change in domain scores from baseline using the patient reported Skindex-16 instrument [ Time Frame: Assessed 12 weeks after Day 1 ]

Estimated Enrollment: 225
Study Start Date: April 2015
Estimated Study Completion Date: October 2018
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: PV-10 (10% rose bengal disodium)
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.
Drug: Dacarbazine, temozolomide or talimogene laherparepvec

Detailed Description:

Subjects will be randomized using a 2:1 treatment allocation (i.e. two-thirds of the subjects will receive PV-10).

Subjects in the comparator arm who have completed at least 1 cycle of study treatment and who meet the study protocol definition of disease progression but do not have evidence of visceral metastases will be eligible to enter the crossover portion of the study and receive PV-10. Subjects crossing over must meet all study inclusion and exclusion criteria for clinical laboratories, thyroid function, concurrent or intercurrent illness and pregnancy at the time of crossover.

Assessment of progression will be performed by an Independent Review Committee (IRC) based on Response Evaluation Criteria in Solid Tumors (RECIST) ver. 1.1 criteria. Events signaling progression include increase in size and/or number of lesions, distant or nodal disease progression, or death. All secondary endpoints involving disease response and progression will be based on the IRC determination.

An interim assessment of efficacy and safety will be performed by the IRC when 50% of the events required for the primary endpoint have occurred.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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. AJCC Stage IIIB, IIIC or Stage IV M1a with no active nodal metastases)
  4. At least 1 cutaneous Target Lesion (each lesion > =10 mm in longest diameter or up to 5 lesions having a sum of longest diameters >= 10 mm). Target Lesions should be at least 10 mm from any other lesion
  5. No lesion > 30 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. Failed, did not tolerate, or not a candidate for treatment with at least one immune checkpoint inhibitor (due to co-morbidities, pre-existing autoimmune disease, drug unavailability or standard of care)
  9. Failed, did not tolerate, or not a candidate for targeted therapy with BRAF or combined BRAF/MEK inhibitors (i.e., 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

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 not using effective contraception (e.g., oral contraceptives, intrauterine devices, double barrier methods such as condoms and diaphragms, abstinence or equivalent measures)
  12. Contraindication for all comparators:

    • Subjects with contraindications to all of the designated comparator drugs
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02288897

Contacts
Contact: Eric Wachter, Ph.D. +1 865 769 4011 ext 23 wachter@pvct.com

Locations
United States, California
Sharp Memorial Hospital - Clinical Oncology Research Recruiting
San Diego, California, United States, 92123
Contact: Cathy Wood    858-939-5062    cathy.wood@sharp.com   
Principal Investigator: Kristen Rice, M.D.         
United States, Florida
Mount Sinai Comprehensive Cancer Center Not yet recruiting
Miami Beach, Florida, United States, 33140
Contact: Christy M Estevez    305-674-2121 ext 53760    Christina.Estevez@msmc.com   
Principal Investigator: Jose Lutzky, MD         
United States, Kentucky
University of Louisville School of Medicine Recruiting
Louisville, Kentucky, United States, 40202
Contact: Mary Healey    502-629-3327    mary.healey@louisville.edu   
Principal Investigator: Charles Scoggins, M.D.         
United States, Missouri
Washington University School of Medicine - Dermatology Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Mary Tabacchi, CCRC    314-362-8171    mtabacchi@wustl.edu   
Principal Investigator: Lynn Cornelius, MD         
United States, New Hampshire
Dartmouth-Hitchcock Medical Center Not yet recruiting
Lebanon, New Hampshire, United States, 03756
Contact: Darcie Findley, CCRC    603-650-4595    darcie.l.findley@hitchcock.org   
Principal Investigator: Keisuke Shirai, MD         
United States, New Jersey
Atlantic Health System Recruiting
Morristown, New Jersey, United States, 07960
Contact: Molly Maurer    973-714-6341    molly.maurer@atlantichealth.org   
Principal Investigator: Eric Whitman, M.D.         
United States, North Carolina
Wake Forest Baptist Health Recruiting
Winston-Salem, North Carolina, United States, 27157
Contact: Angela Howell    336-713-3155    anhowell@wakehealth.edu   
Principal Investigator: Paul Savage, MD, FACP         
United States, Oklahoma
Oklahoma Cancer Specialists and Research Institute Recruiting
Tulsa, Oklahoma, United States, 74146
Contact: Jan Byerly, RN, BSN, OCN    918-505-3201 ext 4076    Jan.Byerly@OCSRI.ORG   
Principal Investigator: Edward Yob, DO         
United States, Pennsylvania
St Luke's University Hospital and Health Network Recruiting
Easton, Pennsylvania, United States, 18045
Contact: Robyn Rex    484-503-4152    Robyn.Rex@sluhn.org   
Principal Investigator: Sanjiv Agarwala, M.D.         
Penn State Hershey Cancer Institute Not yet recruiting
Hershey, Pennsylvania, United States, 17033
Contact: Jennifer Hallman, RN, BSN    717-531-0003 ext 287412    jhallman@pennstatehealth.psu.edu   
Principal Investigator: Rogerio Neves, MD         
United States, Texas
M.D. Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Donna Branham    713-563-3527    dbranham@mdanderson.org   
Principal Investigator: Merrick Ross, M.D.         
United States, Utah
Huntsman Cancer Institute Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Tamara Willis    801-587-4767    Tamara.Willis@hci.utah.edu   
Principal Investigator: Robert Andtbacka, M.D.         
Australia, Queensland
Princess Alexandra Hospital Recruiting
Brisbane, Queensland, Australia, 4102
Contact: Janine Thomas    +61 (07) 3844-8500    Janine.thomas@mater.uq.edu.au   
Principal Investigator: Mark Smithers, M.D.         
Sponsors and Collaborators
Provectus Biopharmaceuticals, Inc.
Investigators
Study Director: Eric Wachter, Ph.D. Provectus Biopharmaceuticals, Inc.
Principal Investigator: Sanjiv Agarwala, M.D. St Luke's University Hospital and Health Network
  More Information

Responsible Party: Provectus Biopharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02288897     History of Changes
Other Study ID Numbers: PV-10-MM-31
Study First Received: November 4, 2014
Last Updated: April 18, 2017

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Temozolomide
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on April 24, 2017