Melanoma
Conditions
Keywords
immune, vaccine, systemic, Metastatic Melanoma (AJCC Stage III or IV)
Brief summary
The primary objective of this study is to investigate the effectiveness of intralesional (IL) PV-10 for locoregional treatment of metastatic melanoma. This study will also include assessment of response in untreated bystander lesions following intralesional injection of PV-10 into targeted lesions. Additional objectives are to determine the safety profile of PV-10 following intralesional injection, and assess the pharmacokinetic profile of PV-10 in the bloodstream following intralesional injection.
Detailed description
This is a multicenter, open-label, single-agent study. Subjects with at least one melanoma lesion ≥ 0.2 cm in diameter that can be accurately measured by ruler/caliper or ultrasound will receive intralesional injection of PV-10 into each of up to twenty (20) Study Lesions. Additionally, one to two measurable Bystander Lesions may remain untreated and will be followed for assessment of bystander response. To accurately reflect anticipated clinical use, repeat dosing of treated lesions will be allowed at the Investigator's discretion at weeks 8, 12 and 16 following initial treatment for those lesions not exhibiting complete response. Subjects will be followed for 52 weeks following initial treatment with PV-10.
Interventions
Intralesional injection for chemoablation
Sponsors
Provectus Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men or women, age 18 years or older. * Histologically or cytologically confirmed metastatic melanoma, AJCC (2002) Stage III (regional lymph node metastasis, in-transit metastasis or satellite metastasis) or Stage IV (distant metastasis). * Measurable disease in at least one lesion ≥ 0.2 cm in diameter that can be accurately measured by ruler/caliper or ultrasound. Target, Non-Target and Bystander Lesions selected by discretion of Investigator. * Performance Status: ECOG 0-2. * Life Expectancy: At least 6 months. * Hematopoietic: * White blood cell count (WBC) no less than 2500/mm3 (2.5 x 10E9/L). * Absolute neutrophil count (ANC) no less than 1,000/mm3 (1.0 x 10E9/L). * Platelet count no less than 90,000/mm3 (90 x 10E9/L). * Blood Chemistry: * Creatinine no greater than 1.5 times the upper limit of normal (ULN). * Total bilirubin no greater than 1.5 times the upper limit of normal (ULN). * AST/ALT no greater than 3 times the upper limit of normal (ULN). * Thyroid Function: * Total T3 or free T3 (serum triiodothyronine), total T4 or free T4 (serum thyroxine) and THS (serum thyrotropin) within normal limits. * Cardiovascular Function: * No clinically significant cardiovascular disease. * Respiratory Function: * No clinically significant respiratory disease. * Immunological Function: * No known immunodeficiency disease. Subjects must have adequate immune system function in the opinion of the Investigator.
Exclusion criteria
* Radiation therapy within 4 weeks of study treatment or to any Study Lesion within 12 weeks of study treatment. * Chemotherapy: * Chemotherapy or other systemic cancer therapy within 4 weeks of study treatment (6 weeks for nitrosoureas or mitomycin). * Regional chemotherapy (limb infusion or perfusion) within 12 weeks of study treatment. * Local treatment (e.g., surgery, cryotherapy, radiofrequency ablation) to the treatment area within 4 weeks of study treatment. * Investigational agents within 4 weeks (or 5 half-lives) of study treatment. * Photosensitizing agents within 5 half-lives of study treatment. * Anti-tumor vaccine therapy within 6 weeks of study treatment. * Concurrent or Intercurrent Illness: * Severe diabetes. * Extremity complications due to diabetes. * Significant concurrent or intercurrent illness, psychiatric disorders, or alcohol or chemical dependence that would, in the opinion of the Investigator, compromise their safety or compliance or interfere with interpretation of study results. * Thyroid disease (subclinical or ongoing), goiter, partial thyroidectomy, previous radioiodine- or surgically-treated Graves' hyperthyroidism or cystic fibrosis, or taking thyroid hormone medication. * Pregnancy: * Female subjects who are pregnant or lactating. * Female subjects who have positive serum ßHCG pregnancy test taken within 7 days of PV-10 treatment. * Fertile subjects who are not using effective contraception.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) of PV-10 Treated Lesions | 52 weeks | Using modified Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for cutaneous or subcutaneous target lesions assessed by ruler, caliper or ultrasound: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Objective Response Rate (ORR) = %CR + %PR. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate of Untreated Bystander Lesions | 52 weeks | Using modified Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for designated, untreated cutaneous or subcutaneous bystander lesions assessed by ruler, caliper or ultrasound: Complete Response (CR), disappearance of all bystander lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of bystander lesions; Objective Response Rate (ORR) = %CR + %PR. |
| Progression Free Survival (PFS) | 52 weeks | Progression is defined using modified Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or significant worsening of non-target disease (e.g., a measurable increase in non-target lesions or the appearance of new lesions) indicative of disease progression. |
| Overall Survival | 52 weeks | 1-year survival |
Countries
Australia, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PV-10 PV-10 (10% rose bengal disodium): Intralesional injection for chemoablation. | 80 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Observation Phase | Additional PV-10 via alternate protocol | 8 |
| Observation Phase | Adverse Event | 1 |
| Observation Phase | Death | 2 |
| Observation Phase | Disease Progression | 55 |
| Observation Phase | Other non-study melanoma treatment | 1 |
| Observation Phase | Physician Decision | 1 |
Baseline characteristics
| Characteristic | PV-10 |
|---|---|
| Age, Continuous | 70.0 years |
| American Joint Committee on Cancer (AJCC) Stage at Baseline IIIB | 38 participants |
| American Joint Committee on Cancer (AJCC) Stage at Baseline IIIC | 24 participants |
| American Joint Committee on Cancer (AJCC) Stage at Baseline M1a | 3 participants |
| American Joint Committee on Cancer (AJCC) Stage at Baseline M1b | 5 participants |
| American Joint Committee on Cancer (AJCC) Stage at Baseline M1c | 10 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0 | 53 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1 | 25 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 2 | 2 participants |
| Number of Prior Interventions | 6 prior interventions |
| Prior Interventions Distal Amputation | 7 participants |
| Prior Interventions Excision | 80 participants |
| Prior Interventions Immunotherapy | 17 participants |
| Prior Interventions Investigational Agents | 11 participants |
| Prior Interventions Nodal Biopsy | 50 participants |
| Prior Interventions Other | 6 participants |
| Prior Interventions Radiotherapy | 17 participants |
| Prior Interventions Regional Chemotherapy | 19 participants |
| Prior Interventions Systemic Chemotherapy | 10 participants |
| Region of Enrollment Australia | 53 participants |
| Region of Enrollment United States | 27 participants |
| Sex: Female, Male Female | 32 Participants |
| Sex: Female, Male Male | 48 Participants |
| Tumor Burden in Skin 10 or more Lesions | 29 participants |
| Tumor Burden in Skin Less than 10 Lesions | 44 participants |
| Tumor Burden in Skin Too Numerous to Count | 7 participants |
| Untreated Disease Burden All Lesions Treated | 28 participants |
| Untreated Disease Burden All Lesions Treated Except Bystanders | 26 participants |
| Untreated Disease Burden One or More Lesions Not Measured and Untreated | 8 participants |
| Untreated Disease Burden Untreated Visceral Disease | 18 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 80 / 80 |
| serious Total, serious adverse events | 14 / 80 |
Outcome results
Primary
Objective Response Rate (ORR) of PV-10 Treated Lesions
Using modified Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for cutaneous or subcutaneous target lesions assessed by ruler, caliper or ultrasound: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Objective Response Rate (ORR) = %CR + %PR.
Time frame: 52 weeks
Population: ITT participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PV-10 | Objective Response Rate (ORR) of PV-10 Treated Lesions | 51.3 percentage of participants |
Secondary
Objective Response Rate of Untreated Bystander Lesions
Using modified Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for designated, untreated cutaneous or subcutaneous bystander lesions assessed by ruler, caliper or ultrasound: Complete Response (CR), disappearance of all bystander lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of bystander lesions; Objective Response Rate (ORR) = %CR + %PR.
Time frame: 52 weeks
Population: ITT participants having at least one uninjected dermal bystander lesion designated at baseline (some ITT participants did not have at least one bystander lesion).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PV-10 | Objective Response Rate of Untreated Bystander Lesions | 33.3 percentage of participants |
Secondary
Overall Survival
1-year survival
Time frame: 52 weeks
Population: ITT participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PV-10 | Overall Survival | 89 percentage of participants |
| Stage IV | Overall Survival | 39 percentage of participants |
Secondary
Progression Free Survival (PFS)
Progression is defined using modified Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or significant worsening of non-target disease (e.g., a measurable increase in non-target lesions or the appearance of new lesions) indicative of disease progression.
Time frame: 52 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PV-10 | Progression Free Survival (PFS) | 3.7 Months |
| Stage IV | Progression Free Survival (PFS) | 1.9 Months |
Post Hoc
Rate of Complete Response
Using modified Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for cutaneous or subcutaneous target lesions assessed by ruler, caliper or ultrasound: Complete Response (CR), disappearance of all target lesions; Complete Response Rate (CRR) = %CR.
Time frame: 52 weeks
Population: ITT participants having all baseline disease injected with PV-10
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PV-10 | Rate of Complete Response | 50 percentage of participants |