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Trial record 9 of 14 for:    Provectus

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

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ClinicalTrials.gov Identifier: NCT02693067
Recruitment Status : Recruiting
First Posted : February 26, 2016
Last Update Posted : April 7, 2017
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Neuroendocrine Tumors Metastatic to the Liver Drug: Rose bengal disodium Phase 1

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.

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : July 2016
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : August 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Carcinoid Tumors
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: PV-10
Intralesional rose bengal disodium (PV-10) to one or more neuroendocrine tumor metastases to the liver
Drug: Rose bengal disodium
Percutaneous intralesional injection to NET tumor
Other Name: PV-10


Outcome Measures

Primary Outcome Measures :
  1. Number of Participants with Adverse Events [ Time Frame: 28 days ]
    Incidence of Systemic and Locoregional Adverse Events will be Coded and Tabulated


Secondary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: 6 months ]
    Response of Injected Target and Measurable Bystander Lesions (if present) will be Tabulated

  2. Target Lesion Somatostatin Receptor (SSTR) Expression [ Time Frame: 6 months ]
    Change in SSTR Expression will be Assessed vs Baseline Values

  3. Change in Neuroendocrine Tumor Biomarkers [ Time Frame: 6 months ]
    Change in Chromogranin A (CgA) and/or 5-Hydroxyindole Acetic Acid (5-HIAA) will be Assessed vs Baseline Values

  4. Reduction in Major Symptoms [ Time Frame: 6 months ]
    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

  5. Reduction in Other Symptoms [ Time Frame: 6 months ]
    Change in Other Symptoms (including Bronchoconstriction and Abdominal Cramping) will be Separately Assessed using QLQ-C30 and GI.NET21 Symptom Scores vs Baseline Values

  6. Change in Peripheral Blood Mononuclear Cells (PBMC) [ Time Frame: 28 days ]
    Change in PBMC will be Assessed vs Baseline Values


Eligibility Criteria

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).
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): NCT02693067


Contacts
Contact: Eric Wachter, Ph.D. +1 865 769 4011 ext 23 wachter@pvct.com
Contact: David Sarson, Ph.D. +612 9489 9220 davidsarson@bigpond.com

Locations
Australia, South Australia
The Queen Elizabeth Hospital Recruiting
Woodville, South Australia, Australia, 5011
Contact: Jessica Reid    +61 08 8222 7779    Jessica.Reid2@sa.gov.au   
Principal Investigator: Timothy Price, M.D.         
Sponsors and Collaborators
Provectus Biopharmaceuticals, Inc.
Investigators
Study Director: Eric Wachter, Ph.D. Provectus Biopharmaceuticals, Inc.
Study Director: David Sarson, Ph.D. Provectus Biopharmaceuticals Australia Pty Ltd
More Information

Responsible Party: Provectus Biopharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02693067     History of Changes
Other Study ID Numbers: PV-10-NET-01
First Posted: February 26, 2016    Key Record Dates
Last Update Posted: April 7, 2017
Last Verified: April 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Neuroendocrine Tumors
Carcinoid Tumor
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial