We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 11 of 14 for:    Provectus

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

This study is currently recruiting participants.
Verified May 2017 by Provectus Pharmaceuticals ( Provectus Biopharmaceuticals, Inc. )
Sponsor:
ClinicalTrials.gov Identifier:
NCT00986661
First Posted: September 30, 2009
Last Update Posted: May 30, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Provectus Pharmaceuticals ( Provectus Biopharmaceuticals, Inc. )
  Purpose
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 Intervention Phase
Cancer Metastatic to the Liver Hepatocellular Carcinoma That is Not Amenable to Resection, Transplant or Other Potentially Curative Therapy Drug: PV-10 (10% rose bengal disodium) Phase 1

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Provectus Pharmaceuticals ( Provectus Biopharmaceuticals, Inc. ):

Primary Outcome Measures:
  • 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:
  • Lesion distribution and retention of PV-10 following injection. [ Time Frame: 3 months ]
  • Objective response rate (ORR) of Target and measurable Bystander Lesions (if present) by 2D EASL criteria. [ Time Frame: 3 months ]
  • Changes in markers of hepatic function, including ALP, ALT, AST, total bilirubin and GGT. [ Time Frame: 3 months ]
  • 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 ]
  • 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 ]

Estimated Enrollment: 66
Study Start Date: October 2009
Estimated Study Completion Date: February 2018
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).

  Hide Detailed Description

Detailed Description:

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

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). Following demonstration of safety and tolerability in the Main Study Group, up to 48 additional subjects with cancers metastatic to the liver or with recurrent HCC will be enrolled into this expansion cohort. 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). 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 (PV-10 plus Sorafenib). Following demonstration of safety and tolerability in the Main Study Group, up to 6 additional subjects with HCC receiving sorafenib at a dose that has been stable and tolerable for at least 4 weeks will be enrolled into each of two successive dose groups in Expansion Cohort 2.

The first 3 subjects will be assigned to Expansion Cohort 2.1 (EC2.1) and will receive PV-10 administered at 0.25 mL PV-10 per cc Lv (up to a maximum dose of 7.5 mL PV-10). If none of the initial 3 subjects experiences dose-limiting toxicity (DLT), defined as onset of any Grade 3 or greater non-hematological (excluding fatigue) or Grade 4 hematological toxicity within 28 days of PV-10 administration that is persistent for 14 days or longer, enrollment in Expansion Cohort 2.2 will commence. If 2 or more of the initial 3 subjects experience a DLT, the combination of PV-10 and sorafenib at this PV-10 dose level will be judged to be intolerable. If one of the initial 3 subjects experiences a DLT, an additional 3 subjects will be enrolled in Expansion Cohort 2.1. If none of these additional subjects experiences a DLT, enrollment in Expansion Cohort 2.2 will commence. If 1 or more of the 3 additional subjects (i.e., ≥ 2 of 6 subjects) experiences a DLT, the combination of PV-10 and sorafenib at this PV-10 dose level will be judged to be intolerable.

If Expansion Cohort 2.1 has been completed with tolerable toxicity, enrollment in Expansion Cohort 2.2 (EC2.2) will commence at a dose of 0.5 mL PV-10 per cc Lv (up to a maximum dose of 15 mL PV-10). If none or 1 of the first 3 subjects enrolled experiences a DLT, the cohort will be expanded to 6 subjects. If no more than 1 subject among 6 experiences a DLT, the dose of 0.5 mL PV-10 per cc Lv will be judged to be the maximum tolerable dose (MTD) for the study. If 2 or more of the 6 subjects experiences a DLT, the combination of PV-10 and sorafenib at this PV-10 dose level will be judged to be intolerable.

If the Expansion Cohort 2.2 dose is not tolerated, Expansion Cohort 2.1 will be expanded to 6 subjects, unless this has already occurred. If more than 1 subject of the 6 experiences a DLT, the Expansion Cohort 2.1 dose of PV-10 plus sorafenib will judged to be intolerable. Otherwise, the Expansion Cohort 2.1 dose will be the MTD for the study.

Subjects in Expansion Cohort 1 or Expansion Cohort 2 with more than one injectable tumor ≥ 1 cm in diameter will be eligible for treatment of an additional injectable tumor 28 days to 120 days 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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00986661


Contacts
Contact: Paul M Goldfarb, M.D. 858 637 7888 gldfrb@aol.com

Locations
United States, California
Sharp Memorial Hospital Recruiting
San Diego, California, United States, 92123
Contact: Cathy Wood, RN, BSN, OCN, CBCN, CCRP    858 939 5062    Cathy.Wood@sharp.com   
Principal Investigator: Paul Goldfarb, M.D.         
United States, Florida
The Southeastern Center for Digestive Disorders & Pancreatic Cancer Recruiting
Tampa, Florida, United States, 33613
Contact: Lindsey Bergman    813-615-7068    Lindsey Bergman <Lindsey.Bergman@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: Melissa Ford, MSN, PhD, RN    615-875-7143    melissa.b.ford@vanderbilt.edu   
Principal Investigator: Daniel Brown, 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

Responsible Party: Provectus Biopharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT00986661     History of Changes
Other Study ID Numbers: PV-10-LC-01
First Submitted: September 24, 2009
First Posted: September 30, 2009
Last Update Posted: May 30, 2017
Last Verified: May 2017

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