Trial Outcomes & Findings for PV-10 vs Chemotherapy or Oncolytic Viral Therapy for Treatment of Locally Advanced Cutaneous Melanoma (NCT NCT02288897)

Last Updated: 2022-01-19

Results Overview

PFS was estimated via Kaplan-Meier analysis using Response Evaluation Criteria In Solid Tumors (RECIST v1.1) criteria. Subjects who did not have an event of progression or death were censored at their last assessment date. Assessment of progression was performed by the sponsor based on review of lesion measurement and clinical progression data reported by each investigator. Events signaling progression included increase in size and/or number of study lesions, onset of visceral metastatic disease, and death. For target lesions (assigned prior to randomization), complete response (CR) required disappearance of all target lesions; partial response (PR) required \>= 30% decrease in sum of the longest diameter (SLD) of all target lesions; progressive disease (PD) required \>=20% increase in SLD of target lesions. Non-target lesions were followed for CR, PD, or non-CR/non-PD status using equivalent thresholds. Progression occurred when PD was observed in either target or non-target lesion.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

20 participants

Primary outcome timeframe

Assessed every 12 weeks until disease progression, withdrawal of consent, or study termination; progression detected between formal assessments was documented at the time of detection; median follow-up time for PFS was 26.6 weeks, maximum was 125.8 weeks.

Results posted on

2022-01-19

Participant Flow

Enrollment open: Apr 2015; first patient treated: Nov 2015; last patient visit completed: Apr 2019

Participant milestones

Participant milestones
Measure	PV-10 (10% Rose Bengal Disodium) Subjects received intralesional PV-10 to all Study Lesions on study Day 1. PV-10 was re-administered at 28-day intervals until complete response, disease progression or study termination.	Chemotherapy or Oncolytic Viral Therapy (Dacarbazine, Temozolomide or Talimogene Laherparepvec) Subjects received (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.
Overall Study STARTED	12	8
Overall Study COMPLETED	12	8
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PV-10 n=12 Participants Subjects received intralesional PV-10 to all Study Lesions on study Day 1. PV-10 was re-administered at 28-day intervals until complete response, disease progression or study termination.	Chemotherapy or Oncolytic Viral Therapy n=8 Participants Subjects received (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.	Total n=20 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Age, Categorical >=65 years	9 Participants n=5 Participants	3 Participants n=7 Participants	12 Participants n=5 Participants
Age, Continuous	79.0 years n=5 Participants	66.8 years n=7 Participants	71.5 years n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	1 Participants n=7 Participants	8 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	7 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants	7 Participants n=7 Participants	18 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	9 participants n=5 Participants	7 participants n=7 Participants	16 participants n=5 Participants
Region of Enrollment Italy	3 participants n=5 Participants	0 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment France	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
American Joint Committee on Cancer (AJCC) Stage at Baseline IIIB-IIID	10 Participants n=5 Participants	7 Participants n=7 Participants	17 Participants n=5 Participants
American Joint Committee on Cancer (AJCC) Stage at Baseline IV-M1a	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: Assessed every 12 weeks until disease progression, withdrawal of consent, or study termination; progression detected between formal assessments was documented at the time of detection; median follow-up time for PFS was 26.6 weeks, maximum was 125.8 weeks.

Population: Subjects receiving PV-10 upon crossover from comparator are not included in the analysis population. Response data from one study center were censored due to resignation of the principal investigator. Because the study was terminated prior to achievement of pre-specified efficacy thresholds (i.e., out of a planned 225 subjects only 20 initiated study treatment), the small number of subjects enrolled precludes scientifically meaningful interpretation of PFS.

Outcome measures

Outcome measures
Measure	PV-10 n=9 Participants Subjects received 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.	Chemotherapy or Oncolytic Viral Therapy n=6 Participants Subjects received (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.
Progression-free Survival (PFS)	6.1 Months Interval 1.5 to 28.9	8.6 Months Interval 1.8 to 14.4

SECONDARY outcome

Timeframe: Assessed every 12 weeks until disease progression, withdrawal of consent, or study termination; median follow-up time for CRR was 26.6 weeks, maximum was 125.8 weeks.

CRR was assessed using RECIST v1.1 criteria, and required disappearance of all target and non-target lesions.

Outcome measures

Outcome measures
Measure	PV-10 n=9 Participants Subjects received 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.	Chemotherapy or Oncolytic Viral Therapy n=6 Participants Subjects received (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.
Complete Response Rate (CRR)	3 Participants	2 Participants

SECONDARY outcome

Timeframe: Assessed every 12 weeks until disease progression, withdrawal of consent, or study termination; median follow-up time for DCR was 26.7 weeks, maximum was 77.7 weeks.

DCR was estimated via Kaplan-Meier analysis for participants achieving a complete response, and was defined as the interval from first complete response to disease progression or death; responders who did not have an event of progression or death were censored at their last assessment date. Complete response was assessed using RECIST v1.1 criteria, and required disappearance of all target and non-target lesions.

Outcome measures

Outcome measures
Measure	PV-10 n=3 Participants Subjects received 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.	Chemotherapy or Oncolytic Viral Therapy n=2 Participants Subjects received (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.
Duration of Complete Response (DCR)	NA Months Could not be estimated due to the low number of events (fewer than 50% of complete responders in the study arm experienced progression prior to study termination).	NA Months Could not be estimated due to the low number of events (fewer than 50% of complete responders in the study arm experienced progression prior to study termination).

SECONDARY outcome

Timeframe: Assessed every 12 weeks upon withdrawal from active study participation until death, withdrawal of consent, or study termination; median follow-up time for survival was 82.4 weeks, maximum was 167.0 weeks.

Population: Subjects were analyzed according to treatment group assignment at randomization.

OS was documented at 12 week intervals commencing on withdrawal from active study participation. Documentation was made by subject clinic visit or other personal contact, telephonic contact, review of medical records, or other unequivocal evidence of survival status. OS was estimated via Kaplan-Meier analysis, and was defined as the interval from randomization to death; subjects who did not have an event of death were censored at their last assessment date.

Outcome measures

Outcome measures
Measure	PV-10 n=12 Participants Subjects received 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.	Chemotherapy or Oncolytic Viral Therapy n=8 Participants Subjects received (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.
Overall Survival (OS)	NA Months Could not be estimated due to the low number of events (fewer than 50% of subjects in the study arm died from any cause prior to study termination).	NA Months Could not be estimated due to the low number of events (fewer than 50% of subjects in the study arm died from any cause prior to study termination).

SECONDARY outcome

Timeframe: Assessed every 4 weeks until 28 days after last treatment; median duration of treatment was 11.8 and 9.5 weeks in each treatment group, respectively.

Population: PV-10 safety population includes two subjects who received PV-10 upon crossover after progression on comparator.

Safety and tolerability were assessed by monitoring the frequency, duration, severity and attribution of adverse events and evaluating changes in laboratory values and vital signs.

Outcome measures

Outcome measures
Measure	PV-10 n=14 Participants Subjects received 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.	Chemotherapy or Oncolytic Viral Therapy n=8 Participants Subjects received (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.
Number of Participants With Adverse Events	14 Participants	8 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Assessed at baseline (Day 1 at start of study treatment) and at the end of each treatment cycle (every 4 or 6 weeks) until disease progression, withdrawal of consent, or study termination; median follow-up time was 26.6 weeks, maximum was 125.8 weeks.

Population: Subjects receiving PV-10 upon crossover from comparator are included in the analysis population for PV-10 (after crossover). Response data from one study center were censored due to resignation of the principal investigator. Because the study was terminated prior to achievement of pre-specified efficacy thresholds (i.e., out of a planned 225 subjects only 20 initiated study treatment), the small number of subjects enrolled precludes scientifically meaningful interpretation of Skindex data.

In this exploratory endpoint, changes in Skindex-16 self-assessment scores were evaluated vs Day 1 baseline domain scores: symptom domain (items 1-4); emotional domain (items 5-11); and functioning domain (items 12-16). The Skindex-16 instrument solicits response to the extent of bother during the preceding week by 16 items (e.g., itching, hurting, worry, impact on daily activities), using a score from 0 (never bothered) to 6 (always bothered) for each item. Item scores are transformed to 0 to 100 scale, and domain scores are calculated as the average of the item scores comprising the domain. A lower domain score at baseline signifies lower impact of that domain; a decrease in domain score from baseline signifies improvement in that domain. Median baseline score and change from baseline over the study interval is presented for each domain.

Outcome measures

Outcome measures
Measure	PV-10 n=10 Participants Subjects received 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.	Chemotherapy or Oncolytic Viral Therapy n=6 Participants Subjects received (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.
Change in Domain Scores From Baseline Using the Patient Reported Skindex-16 Instrument Baseline Symptom Domain Score	2.1 Scores on a Scale (0-100) Standard Error 9.4	18.8 Scores on a Scale (0-100) Standard Error 11.2
Change in Domain Scores From Baseline Using the Patient Reported Skindex-16 Instrument Change in Symptom Domain Score from Baseline	-2.1 Scores on a Scale (0-100) Standard Error 6.0	-6.3 Scores on a Scale (0-100) Standard Error 10.9
Change in Domain Scores From Baseline Using the Patient Reported Skindex-16 Instrument Baseline Emotional Domain Score	20.2 Scores on a Scale (0-100) Standard Error 7.4	16.7 Scores on a Scale (0-100) Standard Error 15.5
Change in Domain Scores From Baseline Using the Patient Reported Skindex-16 Instrument Change in Emotional Domain Score from Baseline	-10.1 Scores on a Scale (0-100) Standard Error 6.3	-4.8 Scores on a Scale (0-100) Standard Error 19.9
Change in Domain Scores From Baseline Using the Patient Reported Skindex-16 Instrument Baseline Functioning Domain Score	1.7 Scores on a Scale (0-100) Standard Error 7.4	8.3 Scores on a Scale (0-100) Standard Error 8.9
Change in Domain Scores From Baseline Using the Patient Reported Skindex-16 Instrument Change in Functioning Domain Score from Baseline	-1.7 Scores on a Scale (0-100) Standard Error 6.1	6.7 Scores on a Scale (0-100) Standard Error 11.0

Adverse Events

PV-10

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Chemotherapy or Oncolytic Viral Therapy

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	PV-10 n=14 participants at risk Subjects received 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. PV-10 (10% rose bengal disodium) PV-10 safety population includes two subjects who received PV-10 upon crossover after progression on comparator	Chemotherapy or Oncolytic Viral Therapy n=8 participants at risk Subjects received (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. Dacarbazine, temozolomide or talimogene laherparepvec
Renal and urinary disorders Glomerulonephritis	0.00% 0/14 • All adverse events occurring between signing the informed consent form and 28 days following final administration of study drug, or that occurred at any time that might be at least possibly related to study drug, were followed until: 1. the event resolved; 2. the subject was lost to follow-up; 3. the event was otherwise explained; or 4. no further improvement or worsening was expected. Median duration of treatment was 11.8 and 9.5 weeks in each treatment group, respectively.	12.5% 1/8 • Number of events 1 • All adverse events occurring between signing the informed consent form and 28 days following final administration of study drug, or that occurred at any time that might be at least possibly related to study drug, were followed until: 1. the event resolved; 2. the subject was lost to follow-up; 3. the event was otherwise explained; or 4. no further improvement or worsening was expected. Median duration of treatment was 11.8 and 9.5 weeks in each treatment group, respectively.

Other adverse events

Additional Information

Eric Wachter, Chief Technology Officer

Provectus Biopharmaceuticals, Inc.

Phone: 865-769-4011

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place