Trial Outcomes & Findings for Phase 2 Study of Intralesional PV-10 for Metastatic Melanoma (NCT NCT00521053)

Last Updated: 2014-08-25

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

80 participants

Primary outcome timeframe

52 weeks

Results posted on

2014-08-25

Participant Flow

Participant milestones

Participant milestones
Measure	PV-10 PV-10 (10% rose bengal disodium): Intralesional injection for chemoablation. In the treatment phase, participants received a single IL injection of PV-10 into each of up to 20 study lesions on day 0 (i.e., one cycle). Treatment cycles could be repeated at weeks 8, 12 and 16 for new non-target lesions or existing target or non-target lesions not exhibiting complete response (i.e., complete disappearance). Participants were observed for 52 weeks. Radiologic assessments of visceral disease status were performed every 12 weeks throughout the study and patients were transitioned into survival follow-up if at any time the investigator identified clinical or radiologic evidence of distant progression. No other melanoma therapy was permitted during the study interval.
Treatment Phase STARTED	80
Treatment Phase Received 1 Cycle of PV-10	35
Treatment Phase Received 2 Cycles of PV-10	26
Treatment Phase Received 3 Cycles of PV-10	16
Treatment Phase Received 4 Cycles of PV-10	3
Treatment Phase COMPLETED	80
Treatment Phase NOT COMPLETED	0
Observation Phase STARTED	80
Observation Phase COMPLETED	12
Observation Phase NOT COMPLETED	68

Reasons for withdrawal

Reasons for withdrawal
Measure	PV-10 PV-10 (10% rose bengal disodium): Intralesional injection for chemoablation. In the treatment phase, participants received a single IL injection of PV-10 into each of up to 20 study lesions on day 0 (i.e., one cycle). Treatment cycles could be repeated at weeks 8, 12 and 16 for new non-target lesions or existing target or non-target lesions not exhibiting complete response (i.e., complete disappearance). Participants were observed for 52 weeks. Radiologic assessments of visceral disease status were performed every 12 weeks throughout the study and patients were transitioned into survival follow-up if at any time the investigator identified clinical or radiologic evidence of distant progression. No other melanoma therapy was permitted during the study interval.
Observation Phase Disease Progression	55
Observation Phase Additional PV-10 via alternate protocol	8
Observation Phase Death	2
Observation Phase Adverse Event	1
Observation Phase Other non-study melanoma treatment	1
Observation Phase Physician Decision	1

Baseline Characteristics

Phase 2 Study of Intralesional PV-10 for Metastatic Melanoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PV-10 n=80 Participants PV-10 (10% rose bengal disodium): Intralesional injection for chemoablation.
Age, Continuous	70.0 years n=93 Participants
Sex: Female, Male Female	32 Participants n=93 Participants
Sex: Female, Male Male	48 Participants n=93 Participants
Region of Enrollment United States	27 participants n=93 Participants
Region of Enrollment Australia	53 participants n=93 Participants
American Joint Committee on Cancer (AJCC) Stage at Baseline IIIB	38 participants n=93 Participants
American Joint Committee on Cancer (AJCC) Stage at Baseline IIIC	24 participants n=93 Participants
American Joint Committee on Cancer (AJCC) Stage at Baseline M1a	3 participants n=93 Participants
American Joint Committee on Cancer (AJCC) Stage at Baseline M1b	5 participants n=93 Participants
American Joint Committee on Cancer (AJCC) Stage at Baseline M1c	10 participants n=93 Participants
Tumor Burden in Skin Less than 10 Lesions	44 participants n=93 Participants
Tumor Burden in Skin 10 or more Lesions	29 participants n=93 Participants
Tumor Burden in Skin Too Numerous to Count	7 participants n=93 Participants
Prior Interventions Excision	80 participants n=93 Participants
Prior Interventions Nodal Biopsy	50 participants n=93 Participants
Prior Interventions Regional Chemotherapy	19 participants n=93 Participants
Prior Interventions Immunotherapy	17 participants n=93 Participants
Prior Interventions Radiotherapy	17 participants n=93 Participants
Prior Interventions Investigational Agents	11 participants n=93 Participants
Prior Interventions Systemic Chemotherapy	10 participants n=93 Participants
Prior Interventions Distal Amputation	7 participants n=93 Participants
Prior Interventions Other	6 participants n=93 Participants
Number of Prior Interventions	6 prior interventions n=93 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0	53 participants n=93 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1	25 participants n=93 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 2	2 participants n=93 Participants
Untreated Disease Burden Untreated Visceral Disease	18 participants n=93 Participants
Untreated Disease Burden One or More Lesions Not Measured and Untreated	8 participants n=93 Participants
Untreated Disease Burden All Lesions Treated Except Bystanders	26 participants n=93 Participants
Untreated Disease Burden All Lesions Treated	28 participants n=93 Participants

PRIMARY outcome

Timeframe: 52 weeks

Population: ITT participants

Outcome measures

Outcome measures
Measure	PV-10 n=80 Participants PV-10 (10% rose bengal disodium): Intralesional injection for chemoablation.	Stage IV Participants reporting Stage IV disease at baseline
Objective Response Rate (ORR) of PV-10 Treated Lesions	51.3 percentage of participants Interval 39.8 to 62.6	—

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	PV-10 n=42 Participants PV-10 (10% rose bengal disodium): Intralesional injection for chemoablation.	Stage IV Participants reporting Stage IV disease at baseline
Objective Response Rate of Untreated Bystander Lesions	33.3 percentage of participants Interval 19.6 to 49.6	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	PV-10 n=62 Participants PV-10 (10% rose bengal disodium): Intralesional injection for chemoablation.	Stage IV n=18 Participants Participants reporting Stage IV disease at baseline
Progression Free Survival (PFS)	3.7 Months Interval 2.9 to 4.5	1.9 Months Interval 1.6 to 2.1

SECONDARY outcome

Timeframe: 52 weeks

Population: ITT participants

1-year survival

Outcome measures

Outcome measures
Measure	PV-10 n=62 Participants PV-10 (10% rose bengal disodium): Intralesional injection for chemoablation.	Stage IV n=18 Participants Participants reporting Stage IV disease at baseline
Overall Survival	89 percentage of participants Interval 1.25 to 13.38	39 percentage of participants

POST_HOC outcome

Timeframe: 52 weeks

Population: ITT participants having all baseline disease injected with PV-10

Outcome measures

Outcome measures
Measure	PV-10 n=28 Participants PV-10 (10% rose bengal disodium): Intralesional injection for chemoablation.	Stage IV Participants reporting Stage IV disease at baseline
Rate of Complete Response	50 percentage of participants Interval 30.6 to 69.4	—

Adverse Events

PV-10

Serious events: 14 serious events

Other events: 80 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	PV-10 n=80 participants at risk PV-10 (10% rose bengal disodium): Intralesional injection for chemoablation.
Cardiac disorders Left ventricular hypertrophy	1.2% 1/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
Hepatobiliary disorders Cholecystitis	1.2% 1/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
General disorders Injection site oedema	1.2% 1/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
General disorders Injection site swelling	2.5% 2/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
General disorders Injection site ulcer	1.2% 1/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
General disorders Pyrexia	1.2% 1/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
Infections and infestations Viral infection	1.2% 1/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
General disorders Injection site necrosis	1.2% 1/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
Cardiac disorders Atrial fibrillation	1.2% 1/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
Infections and infestations Pneumonia	2.5% 2/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
Injury, poisoning and procedural complications Back injury	1.2% 1/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
Injury, poisoning and procedural complications Delayed recovery from anaesthesia	1.2% 1/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
General disorders Injection site pain	2.5% 2/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
General disorders Injection site infection	1.2% 1/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
General disorders Injection site vesicles	1.2% 1/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
Endocrine disorders Pituitary disorder	1.2% 1/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
Skin and subcutaneous tissue disorders Photosensitivity reaction	1.2% 1/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
Gastrointestinal disorders Dysphagia	1.2% 1/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
Musculoskeletal and connective tissue disorders Back pain	1.2% 1/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.

Other adverse events

Other adverse events
Measure	PV-10 n=80 participants at risk PV-10 (10% rose bengal disodium): Intralesional injection for chemoablation.
Gastrointestinal disorders Abdominal pain	5.0% 4/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
Gastrointestinal disorders Constipation	12.5% 10/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
Gastrointestinal disorders Diarrhoea	10.0% 8/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
Gastrointestinal disorders Nausea	21.2% 17/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
Gastrointestinal disorders Vomiting	8.8% 7/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
General disorders Fatigue	6.2% 5/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
General disorders Injection site cellulitis	5.0% 4/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
General disorders Injection site discolouration	31.2% 25/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
General disorders Injection site erythema	13.8% 11/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
General disorders Injection site infection	6.2% 5/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
General disorders Injection site inflammation	7.5% 6/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
General disorders Injection site oedema	40.0% 32/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
General disorders Injection site pain	81.2% 65/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
General disorders Injection site photosensitivity reaction	7.5% 6/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
General disorders Injection site pruritus	21.2% 17/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
General disorders Injection site rash	5.0% 4/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
General disorders Injection site swelling	25.0% 20/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
General disorders Injection site ulcer	5.0% 4/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
General disorders Injection site vesicles	37.5% 30/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
General disorders Injection site warmth	5.0% 4/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
General disorders Lethargy	5.0% 4/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
General disorders Oedema peripheral	6.2% 5/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
Infections and infestations Nasopharyngitis	7.5% 6/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
Metabolism and nutrition disorders Decreased appetite	6.2% 5/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
Musculoskeletal and connective tissue disorders Arthralgia	8.8% 7/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
Musculoskeletal and connective tissue disorders Back pain	5.0% 4/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	6.2% 5/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.
Nervous system disorders Headache	17.5% 14/80 • Adverse event data were collected over the study interval (52 weeks) and followed until resolution. Events on-going at time of withdrawal were followed until resolution or for a period of at least 28 days from last dose of study medication.

Additional Information

Eric Wachter, Chief Technology Officer

Provectus Biopharmaceuticals, Inc.

Phone: 1-865-769-4011

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60