Locally Advanced Cutaneous Melanoma MedDRA version: 21.1 Level: PT Classification code 10025650 Term: Malignant melanoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: PV-10
Pharmaceutical Form: Suspension for injection
CAS Number: 632-69-9
Current Sponsor code: NA
Concentration unit: % percent
Concentration type: equal
Concentration number: 10-
Trade
Sponsors
PROVECTUS BIOPHARMACEUTICALS, INC.
Eligibility
Sex/Gender
All
Inclusion 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: 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 m 2 . • 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). • LDH = 2 times the upper limit of normal (ULN). 11. Thyroid function abnormality = CTCAE Grade 2. 12. Candidate for at least one comparator drug: • Subjects must be candidates for at least one of the designated comparator drugs. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: 1. Presence or history of visceral 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 21 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 progestogenonly 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): The primary study endpoint is progression-free survival (PFS) in the intent-to-treat (ITT) population. Evaluation of progression will be performed by an Independent Review Committee (IRC) based on RECIST ver. 1.1 criteria. Events signaling progression include increase in size and/or number of Study Lesions, distant or nodal disease progression or death. ;Timepoint(s) of evaluation of this end point: La valutazione clinica sarà eseguita a intervalli di 28 giorni durante la fase di trattamento dello studio, a partire dalla fine del primo Ciclo di trattamento e a tutte le visite non programmate durante il follow-up. La valutazione complessiva dello stato della progressione verrà eseguita alla fine del Ciclo di trattamento iniziale e ogni 12 settimane, fino a quando non si verifica una progressione della malattia o la sospensione dello studio. ;Main Objective: The primary objective of this randomized controlled trial (RCT) is to assess the effectiveness of intralesional (IL) PV-10 compared to the Investigator¿s choice of systemic chemotherapy or intralesional oncolytic viral therapy in treating locally advanced cutaneous melanoma. Effectiveness will be assessed by comparison of progression-free survival (PFS) between all intent-to-treat (ITT) subjects in the two study treatment arms.;Secondary Objective: Secondary Objectives ¿ Complete response rate (CRR). ¿ Duration of complete response. ¿ Overall survival (OS). ¿ Safety and tolerability. Exploratory Objectives ¿ Change from Baseline to each visit where the variable is assessed in each of the Skindex-16 self assessment instrument domain scores. ¿Change in Investigator assessed lesion bleeding from Baseline to each visit where clinical evaluation or assessment of progression status is performed. ¿Change in Investigator assessed lesion ulceration from Baseline. ¿Change in Investigator assessed lesion infection from Baseline to each visit where clinical evaluation or assessment of progression | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Endpoint Assessments Efficacy All secondary endpoints involving disease response and progression will be based on the IRC determination. ¿ Complete response rate (CRR) of all ITT subjects will be assessed according to RECIST ver. 1.1 criteria [73] at the end of the Initial Treatment Course and every 12 weeks thereafter until disease progression or study discontinuation occurs. ¿ Duration of complete response, for all ITT subjects who achieve a complete response, will be assessed based on the time from first documentation of complete response until disease progression. ¿ Overall survival (OS) status of all ITT subjects will be assessed by telephone, personal contact (e.g., clinic visit) or other unequivocal documentation of subject status at 12-week intervals commencing at the time of subject transition to Survival Follow-up. ;Timepoint(s) of evaluation of this end point: see the protocol | — |
Countries
Argentina, Australia, France, Germany, Italy, Mexico, Poland, United States
Contacts
Public ContactChief Technology Officer
Provecuts Biopharmaceuticals, Inc
Outcome results
None listed