Clinical Trials /

A Phase 1 Study of PV-10 Chemoablation of Neuroendocrine Tumours (NET) Metastatic to the Liver

NCT02693067

Description:

This study is intended to determine the safety, tolerability and reduction of biochemical markers (Chromogranin A or, if deemed appropriate, 5-hydroxyindoleaceticacid) and troublesome symptoms (particularly diarrhea and flushing) of intralesional injection of PV-10 in subjects with NET metastatic to the liver that are not amenable to resection or other potentially curative therapy.

Related Conditions:
  • Neuroendocrine Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Phase 1 Study of PV-10 Chemoablation of Neuroendocrine Tumours (NET) Metastatic to the Liver
  • Official Title: A Phase 1 Study to Assess the Safety, Tolerability and Effectiveness of PV-10 Chemoablation of Neuroendocrine Tumours (NET) Metastatic to the Liver in the Reduction of Biochemical Markers and Symptoms Caused by Secretory Products

Clinical Trial IDs

  • ORG STUDY ID: PV-10-NET-01
  • NCT ID: NCT02693067

Conditions

  • Neuroendocrine Tumors Metastatic to the Liver

Interventions

DrugSynonymsArms
Rose bengal disodiumPV-10PV-10

Purpose

This study is intended to determine the safety, tolerability and reduction of biochemical markers (Chromogranin A or, if deemed appropriate, 5-hydroxyindoleaceticacid) and troublesome symptoms (particularly diarrhea and flushing) of intralesional injection of PV-10 in subjects with NET metastatic to the liver that are not amenable to resection or other potentially curative therapy.

Detailed Description

      This is a single center, open-label study to evaluate the safety, tolerability, and effect on
      tumor growth and symptomology (clinical and biomarkers) following a single intralesional
      injection of PV-10 in subjects with neuroendocrine tumors metastatic to the liver. Subjects
      will be divided into two cohorts (up to 6 subjects in each), the first of which will receive
      intralesional PV-10 to one liver lesion (to a maximum dose of 15 mL PV-10) to assess safety.
      If safety is established, cohort two will receive treatment to all amenable lesions (to a
      maximum dose of 15 mL PV-10). Subjects can have further lesions treated 6 weeks after their
      initial treatment provided any preceding treatments with PV-10 were well tolerated.
    

Trial Arms

NameTypeDescriptionInterventions
PV-10ExperimentalIntralesional rose bengal disodium (PV-10) to one or more neuroendocrine tumor metastases to the liver
  • Rose bengal disodium

Eligibility Criteria

        Inclusion Criteria:

          1. Age 18 years or older, males and females.

          2. Histologically or cytologically confirmed, or clinically diagnosed based on currently
             accepted standards, NET tumors metastatic to the liver that are not amenable at the
             time of enrolment to resection, transplant or other potentially curative therapy.
             Patients must have at least one common NET symptom (European Organization for Research
             and Treatment of Cancer GI.NET21 instrument score of 2 or more at baseline) including:
             flushing, diaphoresis, diarrhea, abdominal discomfort, hyperacidity, dyspnea or
             palpitations.

          3. The Target Lesion(s) must be determined to be amenable to percutaneous injection by
             the treating physician.

          4. The Target Lesion(s) must have measurable disease, defined as a unidimensionally
             measurable lesion ≥ 1.0 cm in longest diameter by helical computed tomography (CT);
             the maximum diameter of any Target Lesion should be ≤ 3.9 cm. These lesions should
             also overexpress SSTR. If the lesion is negative on positron emission
             tomography-computed tomography (PET/CT), there is no need to perform further PET/CT
             scans.

          5. Performance status of Karnofsky scale 60%-100% or Eastern Cooperative Oncology Group
             (ECOG) performance scale 0-2.

          6. Life expectancy ≥ 6 Months.

          7. Hematopoietic Function

               -  White blood cells (WBC) ≥ 2,500/mm3.

               -  Absolute neutrophil count (ANC) ≥ 1000/mm3.

               -  Hemoglobin ≥ 8 g/dL.

               -  Platelet count ≥ 50,000/mm3.

               -  Coagulation: international normalized ratio (INR) ≤ 1.3.

          8. Blood Chemistry

               -  Aspartate transaminase (AST) and alanine transaminase (ALT) < 5 times Upper Limit
                  of Normal (ULN).

               -  Alkaline phosphatase (ALP) < 5 times ULN.

               -  Bilirubin ≤ 1.5 times ULN.

               -  Creatinine ≤ 1.5 times ULN and estimated glomerular filtration rate (eGFR) ≥ 50.

          9. Thyroid Function

             • Total T3 or free T3 (serum triiodothyronine), total T4 or free T4 (serum thyroxine)
             and TSH (serum thyrotropin) ≤ Common Terminology Criteria for Adverse Events (CTCAE)
             Grade 2 abnormality.

         10. Renal Function

             • Subjects must have adequate renal function in the opinion of the Investigator with
             no clinically significant renal impairment or uncontrolled renal disease, see 8 above.

         11. Cardiovascular Function

             • Subjects must have adequate cardiovascular function in the opinion of the
             Investigator with no clinically significant uncontrolled cardiovascular disease. All
             subjects must have a cardiac echo performed within 12 months to exclude tricuspid
             incompetence ("carcinoid heart syndrome").

         12. Respiratory Function

             • Subjects must have adequate respiratory function in the opinion of the Investigator
             with no clinically significant uncontrolled respiratory disease.

         13. Immunological Function

             • Subjects must have adequate immune system function in the opinion of the
             Investigator with no known immunodeficiency disease.

         14. Long Acting Somatostatin Analogs

             • Subjects on long acting somatostatin analogs must be stable on treatment.
             Somatostatin analogs are to be continued throughout the study period.

         15. Informed Consent: Signed by the subject prior to screening.

        Exclusion Criteria:

          1. Target Lesion(s) must not be contiguous with, encompass or infiltrate major blood
             vessels.

          2. Liver metastases amenable to resection, transplant or other potentially curative
             therapy.

          3. Subjects who have received hepatic surgery, ablation or chemoembolization within 4
             weeks of PV-10 administration.

          4. Radiation Therapy • Subjects who have received hepatic radiation within 4 weeks of
             PV-10 administration.

          5. Chemotherapy

             • Subjects who have received chemotherapy within 4 weeks of PV-10 administration (6
             weeks for nitrosoureas or mitomycin C).

          6. Investigational Agents

             • Subjects who have received investigational agents within 4 weeks (or 5 half-lives)
             of PV-10 administration.

          7. Phototoxic or Photosensitizing Agents

             • Subjects who have received agents posing a clinically significant risk of
             photosensitivity reaction within 5 half-lives of PV-10 administration.

          8. Concurrent or Intercurrent Illness

               -  Subjects with significant concurrent or intercurrent illness, psychiatric
                  disorders or alcohol or chemical dependence that would, in the opinion of the
                  Investigator, compromise their safety or compliance or interfere with
                  interpretation of the study.

               -  Subjects with 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 or radiological presence of ascites.

          9. Pregnancy

               -  Female subjects who are pregnant or lactating.

               -  Female subjects who have positive serum 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:Number of Participants with Adverse Events
Time Frame:28 days
Safety Issue:
Description:Incidence of Systemic and Locoregional Adverse Events will be Coded and Tabulated

Secondary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:6 months
Safety Issue:
Description:Response of Injected Target and Measurable Bystander Lesions (if present) will be Tabulated
Measure:Target Lesion Somatostatin Receptor (SSTR) Expression
Time Frame:6 months
Safety Issue:
Description:Change in SSTR Expression will be Assessed vs Baseline Values
Measure:Change in Neuroendocrine Tumor Biomarkers
Time Frame:6 months
Safety Issue:
Description:Change in Chromogranin A (CgA) and/or 5-Hydroxyindole Acetic Acid (5-HIAA) will be Assessed vs Baseline Values
Measure:Reduction in Major Symptoms
Time Frame:6 months
Safety Issue:
Description:Change in Major Symptoms (Diarrhea and Flushing) will be Separately Assessed using European Organization for Research and Treatment of Cancer QLQ-C30 and GI.NET21 Symptom Scores vs Baseline Values
Measure:Reduction in Other Symptoms
Time Frame:6 months
Safety Issue:
Description:Change in Other Symptoms (including Bronchoconstriction and Abdominal Cramping) will be Separately Assessed using QLQ-C30 and GI.NET21 Symptom Scores vs Baseline Values
Measure:Change in Peripheral Blood Mononuclear Cells (PBMC)
Time Frame:28 days
Safety Issue:
Description:Change in PBMC will be Assessed vs Baseline Values

Details

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

Last Updated

April 5, 2017