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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Provectus Pharmaceuticals
Sponsor:
Information provided by (Responsible Party):
Provectus Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00986661
First received: September 24, 2009
Last updated: February 26, 2014
Last verified: February 2014
  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: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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:

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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Lesion distribution and retention of PV-10 following injection. [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Objective response rate (ORR) of Target and measurable Bystander Lesions (if present) by 2D EASL criteria. [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • Changes in markers of hepatic function, including ALP, ALT, AST, total bilirubin and GGT. [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 42
Study Start Date: October 2009
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: December 2014 (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).

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 24 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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; A documented variceal hemorrhage 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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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: Lisa Obregon, RN, BSN, OCN    858-939-5052    Lisa.Obregon@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: Rose Cabral    484-503-4151    Rosemarie Cabral <Rosemarie.Cabral@sluhn.org>   
Principal Investigator: Sanjiv Agarwala, MD         
Sponsors and Collaborators
Provectus Pharmaceuticals
Investigators
Study Director: Eric Wachter, Ph.D. Provectus Pharmaceuticals
Principal Investigator: Paul M Goldfarb, M.D. Sharp Clinical Oncology Research
  More Information

No publications provided

Responsible Party: Provectus Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00986661     History of Changes
Other Study ID Numbers: PV-10-LC-01
Study First Received: September 24, 2009
Last Updated: February 26, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on September 15, 2014