Clinical Trials /

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

NCT00986661

Description:

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.

Related Conditions:
  • Hepatocellular Carcinoma
  • Metastatic Malignant Neoplasm in the Liver
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study to Assess PV-10 Chemoablation of Cancer of the Liver
  • 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

Clinical Trial IDs

  • ORG STUDY ID: PV-10-LC-01
  • NCT ID: NCT00986661

Conditions

  • Cancer Metastatic to the Liver
  • Hepatocellular Carcinoma That is Not Amenable to Resection, Transplant or Other Potentially Curative
  • Therapy

Interventions

DrugSynonymsArms
PV-10 (10% rose bengal disodium)PV-10 Injection (Intralesional)

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
PV-10 Injection (Intralesional)ExperimentalSubjects in each of three cohorts will receive a single dose of PV-10 to one Target Lesion.
  • PV-10 (10% rose bengal disodium)

Eligibility 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).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:

Secondary Outcome Measures

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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Provectus Biopharmaceuticals, Inc.

Last Updated

May 24, 2017