Symptoms and General Pathology

All Conditions

Neoplasms

Skin and Connective Tissue Diseases

Rare Diseases

Recurrence

Melanoma

Melanoma, Cutaneous Malignant

Skin Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Temozolomide

Dacarbazine

Talimogene laherparepvec

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Immunological

Subjects will receive 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 occurs.

Subjects will receive (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 occurs.

PV-10 (10% rose bengal disodium)

Dacarbazine, temozolomide or talimogene laherparepvec

Eric Wachter, Ph.D.

Sanjiv Agarwala, M.D.

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.

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 study treatment and who meet the study protocol definition of disease progression but do not have evidence of 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 for clinical laboratories, thyroid function, concurrent or intercurrent illness and pregnancy 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.

Blinded review by independent review committee (IRC) for primary and key secondary endpoints.

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

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

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.

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.

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

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.

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.

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.

Provectus Biopharmaceuticals, Inc.

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

PV-10

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

Chemotherapy or Oncolytic Viral Therapy

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.

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

Age, Categorical

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Italy

France

Region of Enrollment

Disease burden was assessed at baseline to characterize melanoma disease stage according to the AJCC 2009 staging system, where stage (I-IV) is based on TNM classification: T refers to tumor size, N refers to lymph node involvement, and M represents metastasis (spread) to other parts of the body. The staging number represents a sum of the TNM classification: a lower stage (i.e., I or II) represents better the prognosis for the patient; the higher the stage (i.e., III or IV), the worse the prognosis.

Participants were not stratified according to stage.

American Joint Committee on Cancer (AJCC) Stage at Baseline

Planned accrual was 225 subjects. However, due to slow accrual during a period of rapid change in global drug development for cutaneous melanoma, the study was terminated early after 20 subjects initiated study treatment. Because the study was terminated prior to achievement of pre-specified efficacy thresholds, the planned central independent review was not conducted and the small number of subjects precluded formal analysis and scientifically meaningful interpretation of efficacy parameters.

Eric Wachter, Chief Technology Officer

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.

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.

Progression-free Survival (PFS)

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 CRR.

Complete Response Rate (CRR)

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.

Duration of Complete Response (DCR)

Subjects were analyzed according to treatment group assignment at randomization.

Overall Survival (OS)

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

Number of Participants With Adverse Events

Baseline Symptom Domain Score

Change in Symptom Domain Score from Baseline

Baseline Emotional Domain Score

Change in Emotional Domain Score from Baseline

Baseline Functioning Domain Score

Change in Functioning Domain Score from Baseline

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.

Spots Global Cancer Trial Database for ivm1a

Every month we try and update this database with for ivm1a cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for ivm1a

Every month we try and update this database with for ivm1a cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for ivm1a cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.