No registrations found.
ID
Source
Brief title
Health condition
metastasized neuroendocrine tumors (NETs)
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint will be the percentage of patients that will have an uptake of
68Ga-DOTATATE in the tumor equal to or above that of the liver after the 14 days
treatment period.
Secondary outcome
• Safety, as number of adverse events
• Drug levels of valproic acid
• Dosimetric evaluation of intra- and intertumoral SSTR2 expression
• Leucocyte methylation analysis
Background summary
Somatostatin receptor type 2 (SSTR2) expressions are of eminent importance for the staging
and treatment of neuroendocrine tumors (NETs). The clinical benefit obtained by treatment
with unlabeled and radiolabeled somatostatin analogues does not apply to the subset of
patients with SSTR2-negative tumors. The lack of these anti-tumoral options could be
responsible for the inferior outcome of these patients compared to those with SSTR2-positive
tumors. Recent in vitro data showed the possibility of upregulating SSTR2 expression in
pancreatic NET cells through treatment with epigenetic drugs. Translating these methods into
clinic could substantially improve diagnostic and treatment options for SSTR2-negative tumors.
The aim of this prospective proof-of-concept study is to increase the expression of the SSTR2
in SSTR2-negative NET patients to levels amenable for somatostatin analogue treatment
through the use of epigenetic drugs.
Study objective
The combined treatment with the epigenetic drugs valproic acid and hydralazine will lead to an increase in SSTR2 expression levels in
patients with metastasized Grade 1 or 2 NETs with low uptake on 68Ga-DOTATATE-PET CT.
Study design
Baseline, 1 & 2 weeks after start of treatment
Intervention
14 days treatment with valproic acid (30mg/kg body weight/day) and hydralazine (150mg / day)
Inclusion criteria
• Age ≥18 years
• Inoperable or metastasized neuroendocrine tumor with well-differentiated histology
(grade 1 or 2)
• SSTR2 negativity on 68Ga DOTATATE PET scan, defined as tumor uptake on 68Ga-
DOTATATE PET CT below that of the liver
Exclusion criteria
• Hypotension, defined as systolic blood pressure <90mmHg
• Heart failure, defined as NYHA III-IV
• Impaired kidney function, defined as creatinine clearance <50ml/min
• Impaired liver function, defined as bilirubin or liver transaminases >3 times upper
normal range
• Uncontrolled hormonal symptoms including severe diarrhea, defined as >5 loose
stools / day
• Severe hypoalbuminemia, defined as serum albumin concentration <25g/L
• Epilepsy
• Known allergies / intolerances to valproic acid or hydralazine
• Existing drug treatment which cannot be stopped and interacts or interferes with
study drugs
• Inability to provide informed consent
• End of life care
Design
Recruitment
IPD sharing statement
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL7726 |
| Other | METC Erasmus MC : MEC-2019-0031 |