Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Digestive System Diseases

Gland and Hormone Related Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Carcinoma

Breast Neoplasms

Pancreatic Neoplasms

Melanoma

Lung Neoplasms

Carcinoma, Hepatocellular

Liver Neoplasms

Carcinoid Tumor

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Adenocarcinoma

Liver Diseases

Pancreatic Cancer

Ocular Melanoma

Intraocular Melanoma

Neuroendocrine Tumor

Neuroepithelioma

Hematinics

All Drugs and Chemicals

Herbal and Botanical

Liver Extracts

Cola

Chrysanthemum

Subjects in each of three cohorts will receive a single dose of PV-10 to one Target Lesion.

Subjects will receive a single injection of PV-10 to a single Target Lesion (0.25 mL PV-10 per cc lesion volume, Lv, or 0.50 mL PV-10 per cc Lv).

PV-10 (10% rose bengal disodium)

Eric Wachter, PhD

This open-label study will evaluate the safety, tolerability, pharmacokinetics and effect on tumor growth following a single intralesional injection of PV-10 in subjects with either (a) hepatocellular carcinoma (HCC) that is not amenable to resection, transplant or other potentially curative therapy or (b) cancer metastatic to the liver.

Subject will be enrolled in one of four planned cohorts (Main Study Group, Expansion Cohort 1, Expansion Cohort 2 or Expansion Cohort 3).

Main Study Group. Three initial subjects with either HCC or cancer metastatic to the liver will receive 0.25 mL PV-10 per cc lesion volume (Lv) to a single lesion (up to a maximum dose of 7.5 mL PV-10). If none of the initial three subjects experiences a new and persistent CTCAE Grade 3 or greater non-hematological or any Grade 4 hematological toxicity over a 28-day follow-up interval, an additional three subjects will be enrolled and similarly treated with PV-10 administered at 0.50 mL per cc Lv (up to a maximum dose of 15 mL PV-10) provided no new and persistent Grade 3 or greater non-hematological or any Grade 4 hematological toxicity occurs.

Expansion Cohort 1 (EC1: PV-10 plus/minus Checkpoint Inhibition). Following demonstration of safety and tolerability in the Main Study Group, up to 48 additional subjects with cancers metastatic to the liver or with HCC will be enrolled into Expansion Cohort 1 (EC1). Subjects will be treated with PV-10 administered at 0.50 mL per cc Lv (up to a maximum dose of 15 mL PV-10). Subjects may receive injection of up to two lesions in any PV-10 treatment cycle. Enrollment will continue provided no new and persistent Grade 3 or greater non-hematological (excluding fatigue) or any Grade 4 hematological toxicity occurs.

Expansion Cohort 2 (EC2: PV-10 plus Checkpoint Inhibition). Following demonstration of safety and tolerability in the Main Study Group, up to 12 additional subjects with HCC on a background of standard care checkpoint inhibition therapy (i.e., anti-PD-1 therapy) will be enrolled into Expansion Cohort 2 (EC2). Subjects will be treated with PV-10 administered at 0.50 mL per cc Lv (up to a maximum dose of 15 mL PV-10). Subjects may receive injection of up to two lesions in any PV-10 treatment cycle. Enrollment will continue provided no new and persistent Grade 3 or greater non-hematological (excluding fatigue) or any Grade 4 hematological toxicity occurs.

Expansion Cohort 3 (EC3: PV-10 plus Checkpoint Inhibition). Following demonstration of safety and tolerability in the Main Study Group, up to 12 additional subjects with hepatic metastases of uveal melanoma (mUM) on a background of standard care checkpoint inhibition therapy (i.e., anti-CTLA-4, anti-PD-1 or combination anti-CTLA-4 and anti-PD-1 therapy) will be enrolled into Expansion Cohort 3 (EC3). Subjects will be treated with PV-10 administered at 0.50 mL per cc Lv (up to a maximum dose of 15 mL PV-10). Subjects may receive injection of up to two lesions in any PV-10 treatment cycle. Enrollment will continue provided no new and persistent Grade 3 or greater non-hematological (excluding fatigue) or any Grade 4 hematological toxicity occurs.

Concomitant therapy with immune checkpoint inhibition is allowed in Expansion Cohort 1 and required in Expansion Cohort 2 and Expansion Cohort 3. This concomitant therapy must commence at least 7 days prior to initial PV-10 administration.

Subjects in each Expansion Cohort one or more additional injectable tumor ≥ 1 cm in diameter will be eligible for treatment of one or more additional injectable tumor 28 days to 6 months after prior PV-10 administration provided that any prior treatments with PV-10 were well tolerated. This may be repeated until all injectable tumors ≥ 1 cm in diameter have received PV-10.

A Study to Assess PV-10 Chemoablation of Cancer of the Liver

A Phase 1 Study to Assess the Safety, Tolerability and Pharmacokinetics of PV-10 Chemoablation of Cancer Metastatic to the Liver or Hepatocellular Carcinoma Not Amenable to Resection or Transplant

Serial correlative samples may be collected from subjects in each Expansion Cohort to evaluate potential changes in subjects' immunologic activity in response to PV-10 treatment; samples will be analyzed at one or more Sponsor-designated central laboratory

Systemic and locoregional Adverse Events (AEs) will be graded by CTCAE v4.0 and coded according to MedDRA; AE data for all subjects in the 1st cohort will be assessed prior to dose escalation. Final assessment use AE data for all subjects

Lesion distribution and retention of PV-10 following injection assessed by CT

Objective response rate (ORR) of Target and measurable Bystander Lesions (if present) by 2D EASL and/or RECIST criteria

Changes in markers of hepatic function, including ALP, ALT, AST, total bilirubin

Pharmacokinetics of PV-10 in the bloodstream following intralesional injection; samples will be obtained immediately prior to PV-10 injection and at 2, 4, 8, 24 and 72 hours, and 7, 14 and 28 days to assess uptake and excretion of PV-10

Overall survival will be assessed for the intent-to-treat population

Provectus Biopharmaceuticals, Inc.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Study to Assess PV-10 Chemoablation of Cancer of the Liver	NCT00986661	Cancer Metastat... Hepatocellular ... Metastatic Mela... Metastatic Ocul... Metastatic Uvea... Metastatic Lung... Metastatic Colo... Metastatic Colo... Metastatic Brea... Metastatic Panc...	PV-10 (10% rose...	18 Years -	Provectus Pharmaceuticals
A Study to Assess PV-10 Chemoablation of Cancer of the Liver	NCT00986661	Cancer Metastat... Hepatocellular ... Metastatic Mela... Metastatic Ocul... Metastatic Uvea... Metastatic Lung... Metastatic Colo... Metastatic Colo... Metastatic Brea... Metastatic Panc...	PV-10 (10% rose...	18 Years -	Provectus Pharmaceuticals

Spots Global Cancer Trial Database for cancer metastatic to the liver