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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):
Provectus Pharmaceuticals ( Provectus Biopharmaceuticals, Inc. )

Tracking Information
First Submitted Date  ICMJE February 23, 2016
First Posted Date  ICMJE February 26, 2016
Last Update Posted Date April 7, 2017
Study Start Date  ICMJE July 2016
Estimated Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 25, 2016)
Number of Participants with Adverse Events [ Time Frame: 28 days ]
Incidence of Systemic and Locoregional Adverse Events will be Coded and Tabulated
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02693067 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 25, 2016)
  • Objective Response Rate (ORR) [ Time Frame: 6 months ]
    Response of Injected Target and Measurable Bystander Lesions (if present) will be Tabulated
  • Target Lesion Somatostatin Receptor (SSTR) Expression [ Time Frame: 6 months ]
    Change in SSTR Expression will be Assessed vs Baseline Values
  • 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
  • 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
  • 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
  • Change in Peripheral Blood Mononuclear Cells (PBMC) [ Time Frame: 28 days ]
    Change in PBMC will be Assessed vs Baseline Values
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase 1 Study of PV-10 Chemoablation of Neuroendocrine Tumours (NET) Metastatic to the Liver
Official Title  ICMJE 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
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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Neuroendocrine Tumors Metastatic to the Liver
Intervention  ICMJE Drug: Rose bengal disodium
Percutaneous intralesional injection to NET tumor
Other Name: PV-10
Study Arms  ICMJE Experimental: PV-10
Intralesional rose bengal disodium (PV-10) to one or more neuroendocrine tumor metastases to the liver
Intervention: Drug: Rose bengal disodium
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 25, 2016)
12
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2020
Estimated Primary Completion Date July 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
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
Listed Location Countries  ICMJE Australia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02693067
Other Study ID Numbers  ICMJE PV-10-NET-01
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Provectus Pharmaceuticals ( Provectus Biopharmaceuticals, Inc. )
Study Sponsor  ICMJE Provectus Biopharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Eric Wachter, Ph.D. Provectus Biopharmaceuticals, Inc.
Study Director: David Sarson, Ph.D. Provectus Biopharmaceuticals Australia Pty Ltd
PRS Account Provectus Pharmaceuticals
Verification Date April 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP