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:
  • Malignant Solid Tumor
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
  • Metastatic Melanoma
  • Metastatic Ocular Melanoma
  • Metastatic Uveal Melanoma
  • Metastatic Lung Cancer
  • Metastatic Colon Cancer
  • Metastatic Colorectal Cancer
  • Metastatic Breast Cancer
  • Metastatic Pancreatic Cancer

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 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.
    

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.

          -  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 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:Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of hepatic administration of PV-10
Time Frame:28 days
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:PV-10 distribution
Time Frame:3 months
Safety Issue:
Description:Lesion distribution and retention of PV-10 following injection assessed by CT
Measure:Objective response rate (ORR)
Time Frame:3 months
Safety Issue:
Description:Objective response rate (ORR) of Target and measurable Bystander Lesions (if present) by 2D EASL and/or RECIST criteria
Measure:Changes in markers of hepatic function
Time Frame:3 months
Safety Issue:
Description:Changes in markers of hepatic function, including ALP, ALT, AST, total bilirubin
Measure:Pharmacokinetics of PV-10
Time Frame:28 days
Safety Issue:
Description: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
Measure:Overall survival
Time Frame:Assessed every 3 months for up to 100 months
Safety Issue:
Description:Overall survival will be assessed for the intent-to-treat population

Details

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

Trial Keywords

  • melanoma
  • uveal
  • ocular
  • mUM
  • mOM
  • OM
  • UM
  • pancreatic
  • colon
  • colorectal
  • lung
  • metastatic
  • carcinoid
  • neuroendocrine
  • liver
  • hepatic

Last Updated

March 19, 2021