Clinical Trials Logo

Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT00986661
Other study ID # PV-10-LC-01
Secondary ID
Status Active, not recruiting
Phase Phase 1
First received
Last updated
Start date October 2009
Est. completion date February 2023

Study information

Verified date October 2022
Source Provectus Pharmaceuticals
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


Description:

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.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 78
Est. completion date February 2023
Est. primary completion date December 2022
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Age 18 years or older, males and females. - Histologically or cytologically confirmed, or clinically diagnosed based on currently accepted standards, cancer metastatic to the liver or HCC that is not amenable at the time of enrollment to resection, transplant or other potentially curative therapy. - At least one Target Lesion determined to be amenable to percutaneous injection by the treating physician. - Target Lesion(s) must have measurable disease, defined as a unidimensionally measurable lesion = 1.0 cm in longest diameter by helical CT; the maximum diameter of Target Lesion(s) shall be = 4.9 cm. - Performance status of Karnofsky scale 60%-100% or ECOG performance scale 0-2. - Life expectancy = 12 weeks. - Hematopoietic Function: WBC = 2,500/mm3; ANC = 1000/mm3; Hemoglobin = 8 g/dL; Platelet count = 50,000/mm3; Coagulation: INR = 1.3. - AST and ALT < 5 times ULN; ALP < 5 times ULN; Bilirubin = 1.5 times ULN; Creatinine = 1.5 times ULN and eGFR = 50. - Thyroid Function: Total T3 or free T3, total T4 or free T4 and THS = CTCAE Grade 2 abnormality. - Renal Function: Adequate renal function in the opinion of the Investigator with no clinically significant renal impairment or uncontrolled renal disease. - Cardiovascular Function: Adequate cardiovascular function in the opinion of the Investigator with no clinically significant uncontrolled cardiovascular disease. - Respiratory Function: Adequate respiratory function in the opinion of the Investigator with no clinically significant uncontrolled respiratory disease. - Immunological Function: Adequate immune system function in the opinion of the Investigator with no known immunodeficiency disease. - Informed Consent: Signed by the subject prior to screening. Exclusion Criteria: - Target Lesion(s) must not be contiguous with, encompass or infiltrate major blood vessels. - Primary HCC amenable to resection, transplant or other potentially curative therapy. - Surgery: Subjects who have received hepatic surgery, ablation or chemoembolization within 4 weeks of PV-10 administration. - Radiation Therapy: Hepatic radiation within 4 weeks of PV-10 administration. - Chemotherapy: Chemotherapy within 4 weeks of PV-10 administration (6 weeks for nitrosoureas or mitomycin C). - Investigational Agents: Investigational agents within 4 weeks (or 5 half-lives) of PV-10 administration. - Phototoxic or Photosensitizing Agents: Concomitant agents posing a clinically significant risk of photosensitivity reaction within 5 half-lives of PV-10 administration. - Concurrent or Intercurrent Illness: Impaired wound healing due to diabetes; Significant concurrent or intercurrent illness, psychiatric disorders or alcohol or chemical dependence that would compromise Subject safety or compliance or interfere with interpretation of the study; Uncontrolled thyroid disease or cystic fibrosis; Presence of clinically significant acute or unstable cardiovascular, cerebrovascular (stroke), renal, gastrointestinal, pulmonary, immunological (with the exception of the presence of hepatitis B virus (HBV), viral hepatitis, or cirrhosis), endocrine, or central nervous system disorders; Current encephalopathy or current treatment for encephalopathy; Variceal bleeding requiring hospitalization or transfusion within 4 months of screening; History of human immunodeficiency virus or acquired immune deficiency syndrome; The clinical presence of ascites. - Pregnancy: Female subjects who are pregnant, lactating or have positive serum ß HCG pregnancy test taken within 7 days of PV-10 administration; Fertile subjects who are not using effective contraception (e.g., oral contraceptives, intrauterine devices, double barrier methods such as condoms and diaphragms, abstinence or equivalent measures).

Study Design


Intervention

Drug:
PV-10 (10% rose bengal disodium)
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).

Locations

Country Name City State
United States St Luke's University Health Network Bethlehem Pennsylvania
United States MD Anderson Cancer Center Houston Texas
United States Vanderbilt University Medical Center Nashville Tennessee
United States Sharp Memorial Hospital San Diego California
United States Florida Hospital Tampa Tampa Florida

Sponsors (1)

Lead Sponsor Collaborator
Provectus Biopharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Other Exploratory Correlative Endpoints 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 28 days
Primary Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of hepatic administration of PV-10 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 28 days
Secondary PV-10 distribution Lesion distribution and retention of PV-10 following injection assessed by CT 3 months
Secondary Objective response rate (ORR) Objective response rate (ORR) of Target and measurable Bystander Lesions (if present) by 2D EASL and/or RECIST criteria 3 months
Secondary Changes in markers of hepatic function Changes in markers of hepatic function, including ALP, ALT, AST, total bilirubin 3 months
Secondary Pharmacokinetics of PV-10 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 28 days
Secondary Overall survival Overall survival will be assessed for the intent-to-treat population Assessed every 3 months for up to 100 months
See also
  Status Clinical Trial Phase
Recruiting NCT04209491 - Interest of the Intervention of a Nurse Coordinator in Complex Care Pathway
Completed NCT03963206 - Cabozantinib toLERANCE Study in HepatoCellular Carcinoma (CLERANCE) Phase 4
Completed NCT03268499 - TACE Emulsion Versus Suspension Phase 2
Recruiting NCT05044676 - Immune Cells as a New Biomarker of Response in Patients Treated by Immunotherapy for Advanced Hepatocellular Carcinoma
Recruiting NCT05263830 - Glypican-3 as a Prognostic Factor in Patients With Hepatocellular Carcinoma Treated by Immunotherapy
Recruiting NCT05095519 - Hepatocellular Carcinoma Imaging Using PSMA PET/CT Phase 2
Recruiting NCT05497531 - Pilot Comparing ctDNA IDV vs. SPV Sample in Pts Undergoing Biopsies for Hepatobiliary and Pancreatic Cancers N/A
Completed NCT05068193 - A Clinical Trial to Compare the Pharmacokinetics and Bioequivalence of "BR2008" With "BR2008-1" in Healthy Volunteers Phase 1
Active, not recruiting NCT03781934 - A Study to Evaluate MIV-818 in Patients With Liver Cancer Manifestations Phase 1/Phase 2
Terminated NCT03655613 - APL-501 or Nivolumab in Combination With APL-101 in Locally Advanced or Metastatic HCC and RCC Phase 1/Phase 2
Active, not recruiting NCT03170960 - Study of Cabozantinib in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors Phase 1/Phase 2
Active, not recruiting NCT04242199 - Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of INCB099280 in Participants With Advanced Solid Tumors Phase 1
Completed NCT04401800 - Preliminary Antitumor Activity, Safety and Tolerability of Tislelizumab in Combination With Lenvatinib for Hepatocellular Carcinoma Phase 2
Withdrawn NCT05418387 - A Social Support Intervention to Improve Treatment Among Hispanic Kidney and Liver Cancer Patients in Arizona N/A
Active, not recruiting NCT04039607 - A Study of Nivolumab in Combination With Ipilimumab in Participants With Advanced Hepatocellular Carcinoma Phase 3
Terminated NCT03970616 - A Study of Tivozanib in Combination With Durvalumab in Subjects With Advanced Hepatocellular Carcinoma Phase 1/Phase 2
Recruiting NCT06239155 - A Phase I/II Study of AST-3424 in Subjects With Advanced Solid Tumors Phase 1/Phase 2
Recruiting NCT04118114 - Phase II Study of PRL3-ZUMAB in Advanced Solid Tumors Phase 2
Recruiting NCT03642561 - Evaluation the Treatment Outcome for RFA in Patients With BCLC Stage B HCC in Comparison With TACE Phase 2/Phase 3
Completed NCT03222076 - Nivolumab With or Without Ipilimumab in Treating Patients With Resectable Liver Cancer Phase 2