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

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief 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.

Condition or disease	Intervention/treatment	Phase
Cancer Metastatic to the Liver; Hepatocellular Carcinoma	Drug: PV-10 (10% rose bengal disodium)	Phase 1

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Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	66 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	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
Study Start Date :	October 2009
Estimated Primary Completion Date :	December 2019
Estimated Study Completion Date :	February 2020

Arms and Interventions

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Arm	Intervention/treatment
Experimental: PV-10 Injection (Intralesional); Subjects in each of three cohorts will receive a single dose of PV-10 to one Target Lesion.	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).

Outcome Measures

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Primary Outcome Measures :

1. Safety. 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. [ Time Frame: 28 days ]

Secondary Outcome Measures :

1. Lesion distribution and retention of PV-10 following injection. [ Time Frame: 3 months ]
2. Objective response rate (ORR) of Target and measurable Bystander Lesions (if present) by 2D EASL criteria. [ Time Frame: 3 months ]
3. Changes in markers of hepatic function, including ALP, ALT, AST, total bilirubin and GGT. [ Time Frame: 3 months ]
4. 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. [ Time Frame: 28 days ]
5. Pharmacokinetics of sorafenib 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 impact of PV-10 on sorafenib levels. [ Time Frame: 28 days ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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.
• The Target Lesion must be determined to be amenable to percutaneous injection by the treating physician.
• The Target Lesion must have measurable disease, defined as a unidimensionally measurable lesion ≥ 1.0 cm in longest diameter by helical CT; the maximum diameter of the Target Lesion 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). Subjects with HCC who have been on a stable dose of sorafenib for at least 4 weeks will be candidates for enrollment in Expansion Cohort 2.
• 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 β 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).

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Contacts

Contact: Paul M Goldfarb, M.D.	858 637 7888	gldfrb@aol.com
Contact: Eric Wachter, Ph.D.	865-769-4011 ext 23	wachter@pvct.com

Locations

United States, California
Sharp Memorial Hospital	Recruiting
San Diego, California, United States, 92123
Contact: Amy King 858-939-5052 Amy.King@sharp.com
Principal Investigator: Kristin Rice, M.D.
United States, Florida
Florida Hospital Tampa	Recruiting
Tampa, Florida, United States, 33613
Contact: Heather Bingaman, BS 813-615-7068 heather.bingaman@ahss.org
Principal Investigator: Alexander Rosemurgy, M.D.
United States, Pennsylvania
St Luke's University Health Network	Recruiting
Bethlehem, Pennsylvania, United States, 18015
Contact: Alyse M LaLiberte, MPH 484-503-4151 Alyse.LaLiberte@sluhn.org
Contact: Robyn Rex, RN, OCN, CCRP 484-503-4152 robyn.rex@sluhn.org
Principal Investigator: Sanjiv Agarwala, MD
United States, Tennessee
Vanderbilt University Medical Center	Recruiting
Nashville, Tennessee, United States, 37232
Contact: Rhonda Combs, LPN 615-322-2260 rhonda.j.combs@vanderbilt.edu
Contact: Melissa Ford, MSN, PhD, RN 615-875-7143 melissa.b.ford@vanderbilt.edu
Principal Investigator: Daniel Brown, MD
United States, Texas
MD Anderson Cancer Center	Recruiting
Houston, Texas, United States, 77030
Contact: Gener Balmes, RN, CCRP 713-794-4153 gcbalmes@mdanderson.org
Principal Investigator: Sapna Patel, MD

Sponsors and Collaborators

Provectus Biopharmaceuticals, Inc.

Investigators

Study Director:	Eric Wachter, Ph.D.	Provectus Biopharmaceuticals, Inc.
Principal Investigator:	Paul M Goldfarb, M.D.	Sharp Clinical Oncology Research

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Provectus Biopharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT00986661 History of Changes
Other Study ID Numbers:	PV-10-LC-01
First Posted:	September 30, 2009
Last Update Posted:	April 26, 2018
Last Verified:	April 2018

Keywords provided by Provectus Pharmaceuticals ( Provectus Biopharmaceuticals, Inc. ):

melanoma; uveal; ocular; mUM; mOM; OM; UM	pancreatic; colon; colorectal; lung; metastatic; carcinoid; neuroendocrine

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Hepatocellular; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Adenocarcinoma	Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases