Trial from ClinicalTrials.gov

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Trial ID
NCT02693067
Ethics application status
Date submitted
23/02/2016
Date registered
23/02/2016
Date last updated
5/04/2017

Titles & IDs
Public title
A Phase 1 Study of PV-10 Chemoablation of Neuroendocrine Tumours (NET) Metastatic to the Liver
Scientific 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
Secondary ID [1] 0 0
PV-10-NET-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neuroendocrine Tumors Metastatic to the Liver 0 0
Condition category
Condition code
Cancer 0 0 0 0
Neuroendocrine tumour (NET)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: drugs - Rose bengal disodium

Experimental: PV-10 - Intralesional rose bengal disodium (PV-10) to one or more neuroendocrine tumor metastases to the liver


Treatment: drugs: Rose bengal disodium
Percutaneous intralesional injection to NET tumor

Intervention code [1] 0 0
Treatment: drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants with Adverse Events - Incidence of Systemic and Locoregional Adverse Events will be Coded and Tabulated
Timepoint [1] 0 0
28 days
Secondary outcome [1] 0 0
Objective Response Rate (ORR) - Response of Injected Target and Measurable Bystander Lesions (if present) will be Tabulated
Timepoint [1] 0 0
6 months
Secondary outcome [2] 0 0
Target Lesion Somatostatin Receptor (SSTR) Expression - Change in SSTR Expression will be Assessed vs Baseline Values
Timepoint [2] 0 0
6 months
Secondary outcome [3] 0 0
Change in Neuroendocrine Tumor Biomarkers - Change in Chromogranin A (CgA) and/or 5-Hydroxyindole Acetic Acid (5-HIAA) will be Assessed vs Baseline Values
Timepoint [3] 0 0
6 months
Secondary outcome [4] 0 0
Reduction in Major Symptoms - 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
Timepoint [4] 0 0
6 months
Secondary outcome [5] 0 0
Reduction in Other Symptoms - Change in Other Symptoms (including Bronchoconstriction and Abdominal Cramping) will be Separately Assessed using QLQ-C30 and GI.NET21 Symptom Scores vs Baseline Values
Timepoint [5] 0 0
6 months
Secondary outcome [6] 0 0
Change in Peripheral Blood Mononuclear Cells (PBMC) - Change in PBMC will be Assessed vs Baseline Values
Timepoint [6] 0 0
28 days

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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).

Study design
Purpose of the study
Treatment
Allocation to intervention
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Current
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
The Queen Elizabeth Hospital - Woodville
Recruitment postcode(s) [1] 0 0
5011 - Woodville

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Provectus Biopharmaceuticals, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Eric Wachter, Ph.D.
Address 0 0
Provectus Biopharmaceuticals, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Eric Wachter, Ph.D.
Address 0 0
Country 0 0
Phone 0 0
+1 865 769 4011
Fax 0 0
Email 0 0
wachter@pvct.com
Contact person for scientific queries
Contact person responsible for updating information