TheranosticTrials.org

Clinical Trial · NCT05178693

Lutathera and ASTX727 in Neuroendocrine Tumours

Overview

Patients entered into the study will receive ASTX727 orally for 5 days, prior to receiving Lutathera treatment on Day 8, to determine whether pre-treatment with ASTX727 results in re-expression of somatostatin receptor-2 in patients with metastatic neuroendocrine tumours. The study will use \[68Ga\]-DOTA-TATE PET to image epigenetic modification of the receptor locus.

Sponsor

Imperial College London

Phase

Phase 1

Contacts

Rohini Sharma, Professor (PRINCIPAL_INVESTIGATOR)

Rohini Sharma, Professor (CONTACT)

rohini.sharma2@nhs.net

02083833170

ClinicalTrials.gov

NCT05178693

Drug / Compound

DOTATATE

Isotope(s):
Target(s):
  • SSTR2
Ligand Class: Peptides
Chelator: DOTA

DOTATATE

Isotope(s):
Target(s):
  • SSTR2
Ligand Class: Peptides
Chelator: DOTA

Eligibility

Inclusion

  • No tumoural uptake on \[68Ga\]-DOTA-TATE or uptake less than background liver
  • Progression or intolerance to first line therapy including somatostatin analogues
  • Adequate organ function as outlined in the protocol
  • Women of childbearing potential must be willing to use a highly effective method of contraception as outlined in the protocol for the course of the study through 6 months after the last dose of Investigational Medicinal Product (IMP). Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subjects
  • Have disease that can be readily biopsied by ultrasound guidance (n=5)
  • Measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
  • Histologic or cytologic confirmed diagnosis of neuroendocrine tumour
  • Have archival tissue block available or willing to have fresh tissue biopsy if blocks not available
  • ECOG Performance status 0 - 2
  • Sexually active males must agree to use an adequate method of contraception as outlined in the protocol starting with the first dose of IMP through 6 months after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject
  • Ki67 \< 55% (only patients with well differentiated grade 1-3 NETs will be included in the study as patients with poorly differentiated grade 3 NETs have a prognosis of less than 6 months)

Exclusion

  • Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through to 6 months after the last dose of IMP.
  • Has a known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is required unless mandated by local health authority.
  • Has received a live vaccine within 30 days of first dose of ASTX727 administration. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
  • Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease and stereotactic radiotherapy to the CNS
  • Is currently participating and receiving therapy or has participated or is participating in a study of an IMP or used an investigational device within 4 weeks of the first dose of IMP.
  • Serious concurrent medical illness, including serious active infection
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating Principal Investigator (PI).
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Previous treatment with either study medication and/or known hypersensitivity to the study medication
  • Has a known history of active Bacillus Tuberculosis (TB).
  • Bleeding or thrombotic disorders or subjects at risk for severe haemorrhage
  • Other clinically significant co-morbidities that could compromise the subject's participating in the study
  • History of organ transplant