Clinical Trials /

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

NCT02288897

Description:

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.

Related Conditions:
  • Melanoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

PV-10 Intralesional Injection vs <span class="go-doc-concept go-doc-intervention">Systemic Chemotherapy</span> for Treatment of Locally Advanced Cutaneous <span class="go-doc-concept go-doc-disease">Melanoma</span>

Title

  • Brief Title: PV-10 Intralesional Injection vs Systemic Chemotherapy for Treatment of Locally Advanced Cutaneous Melanoma
  • Official Title: PV-10 Intralesional Injection vs Systemic Chemotherapy for Treatment of Locally Advanced Cutaneous Melanoma Without Distant Metastases
  • Clinical Trial IDs

    NCT ID: NCT02288897

    ORG ID: PV-10-MM-31

    Trial Conditions

    Melanoma Recurrent

    Trial Interventions

    Drug Synonyms Arms
    PV-10 (10% rose bengal disodium) PV-10
    Dacarbazine or temozolomide Systemic Chemotherapy

    Trial Purpose

    This is an international multicenter, open-label, randomized controlled trial (RCT) of
    single-agent intralesional PV-10 versus systemic chemotherapy with dacarbazine (DTIC) or
    temozolomide (TMZ) to assess treatment of locally advanced cutaneous melanoma in patients
    who are BRAF V600 wild-type and 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 or temozolomide as determined by Investigator preference and/or local
    availability of the agent. Effectiveness will be assessed by comparison of progression-free
    survival (PFS) between all intent-to-treat (ITT) subjects in the two study treatment arms.

    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 dacarbazine or
    temozolomide and who meet the study protocol definition of disease progression but do not
    have evidence of distant cutaneous, subcutaneous, active nodal or 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 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.

    Trial Arms

    Name Type Description Interventions
    PV-10 Experimental Subjects will receive intralesional PV-10 to all Study Lesions on study Day 1. PV-10 should be re-administered at Day 29 (Week 5) and/or Day 57 (Week 9) for treatment of any existing disease on the skin and thereafter at 28-day intervals until complete response, disease progression or study termination occurs. PV-10 (10% rose bengal disodium)
    Systemic Chemotherapy Active Comparator Subjects will receive systemic dacarbazine (intravenously at 850 m/m2) or oral temozolomide (orally at 200 mg/m2 daily for 5 consecutive days), initially administered over three consecutive 28-day cycles. Dacarbazine or temozolomide should be continued on a 28-day cycle until complete response, disease progression or study termination occurs. Dacarbazine or temozolomide

    Eligibility Criteria

    Inclusion Criteria:

    1. Age 18 years or older, male or female

    2. Histologically or cytologically confirmed melanoma

    3. Stage IIIB or IIIC recurrent, satellite or in-transit cutaneous or subcutaneous
    melanoma

    4. At least 1 cutaneous Target Lesion > =10 mm in longest diameter. Target Lesions
    should be at least 10 mm from any other lesion

    5. No lesion > 30 mm in longest diameter; and no more than 20 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 (due to co-morbidities, pre-existing
    autoimmune disease or drug unavailability) treatment with ipilimumab or another
    immune checkpoint inhibitor

    9. Not a candidate for treatment with vemurafenib, dabrafenib or trametinib (i.e., BRAF
    V600 wild-type)

    10. Life Expectancy: At least 6 months.

    11. 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).

    12. Thyroid function abnormality Grade 2

    Exclusion Criteria:

    1. Presence or history of visceral or distant cutaneous or subcutaneous melanoma
    metastasis

    2. Presence of active nodal metastasis

    3. Presence of more than 20 melanoma lesions

    4. Radiation therapy to any Study Lesion within 4 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 (or 5 half-lives) 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)

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Progression-free survival (PFS)

    Secondary Outcome Measures

    Complete response rate (CRR)

    Duration of complete response

    Overall survival (OS)

    Number of participants with adverse events

    Trial Keywords