We updated the design of this site on December 18, 2017. Learn more.
ClinicalTrials.gov
ClinicalTrials.gov Menu
IMPORTANT: Due to the lapse in government funding, the information on this web site may not be up to date, transactions submitted via the web site may not be processed, and the agency may not be able to respond to inquiries until appropriations are enacted. Updates regarding government operating status and resumption of normal operations can be found at opm.gov.

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02288897
Recruitment Status : Recruiting
First Posted : November 11, 2014
Last Update Posted : January 19, 2018
Sponsor:
Information provided by (Responsible Party):

Study Description
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.

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

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.


Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 225 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Masking Description: Blinded review by independent review committee (IRC) for primary and key secondary endpoints.
Primary Purpose: Treatment
Official Title: PV-10 Intralesional Injection vs Systemic Chemotherapy or Oncolytic Viral Therapy for Treatment of Locally Advanced Cutaneous Melanoma
Study Start Date : April 2015
Estimated Primary Completion Date : September 2018
Estimated Study Completion Date : October 2018


Arms and Interventions

Arm Intervention/treatment
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


Outcome Measures

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

Secondary Outcome Measures :
  1. Complete response rate (CRR) [ Time Frame: Assessed every 12 weeks up to 18 months ]
  2. Duration of complete response [ Time Frame: Assessed every 12 weeks up to 18 months ]
  3. Overall survival (OS) [ Time Frame: Assessed every 12 weeks up to 18 months ]
  4. 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:
  1. Change in domain scores from baseline using the patient reported Skindex-16 instrument [ Time Frame: Assessed 12 weeks after Day 1 ]

Eligibility Criteria

Information from the National Library of Medicine

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, Learn About Clinical Studies.


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 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

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
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02288897


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

  Show 21 Study Locations
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
First Posted: November 11, 2014    Key Record Dates
Last Update Posted: January 19, 2018
Last Verified: January 2018

Keywords provided by Provectus Pharmaceuticals ( Provectus Biopharmaceuticals, Inc. ):
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

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