Combining ASTX727 with Lutathera for Neuroendocrine Tumors

The Epigenetic Modification of Somatostatin Receptor-2 to Improve Therapeutic Outcome With Lutathera in Patients With Metastatic Neuroendocrine Tumours.

This study is testing whether taking ASTX727 for five days before Lutathera treatment can help people with metastatic neuroendocrine tumors by looking at changes in a specific receptor.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 27 (estimated)
• Ages: 18 Years to 99 Years
• Sex: All
• Sponsor: Imperial College London (Academic / other)
• Drugs / interventions: radiation
• Locations: 1 site (London, London, City of)
• Trial ID: NCT05178693 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effects of pre-treatment with ASTX727 on the re-expression of somatostatin receptor-2 in patients with metastatic neuroendocrine tumors. Eligible participants will take ASTX727 orally for five days before receiving Lutathera treatment on Day 8. The study aims to assess the efficacy of this combination therapy using imaging techniques to monitor changes in the receptor locus. Patients will undergo multiple treatment cycles and be monitored for disease progression and treatment response.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and over with well-differentiated neuroendocrine tumors who have progressed on first-line therapy.

Not a fit: Patients with poorly differentiated neuroendocrine tumors or those who do not meet the specific inclusion criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could enhance the effectiveness of Lutathera in treating neuroendocrine tumors.

How similar studies have performed: While this approach is innovative, similar studies have shown promise in enhancing treatment responses in neuroendocrine tumors.

Eligibility criteria

Inclusion Criteria:

1. Be willing and able to provide written informed consent for the trial.
2. Be aged 18 or over at the day of signing consent
3. Histologic or cytologic confirmed diagnosis of neuroendocrine tumour
4. Have archival tissue block available or willing to have fresh tissue biopsy if blocks not available
5. Have disease that can be readily biopsied by ultrasound guidance (n=5)
6. 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)
7. Progression or intolerance to first line therapy including somatostatin analogues
8. ECOG Performance status 0 - 2
9. No tumoural uptake on \[68Ga\]-DOTA-TATE or uptake less than background liver
10. 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
11. Adequate organ function as outlined in the protocol
12. 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
13. 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

Exclusion Criteria:

1. Previous treatment with either study medication and/or known hypersensitivity to the study medication
2. Serious concurrent medical illness, including serious active infection
3. History of organ transplant
4. Has a known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is required unless mandated by local health authority.
5. Has a known history of active Bacillus Tuberculosis (TB).
6. 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.
7. Bleeding or thrombotic disorders or subjects at risk for severe haemorrhage
8. 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.
9. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
10. 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).
11. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
12. 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.
13. 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.
14. 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
15. Other clinically significant co-morbidities that could compromise the subject's participating in the study

Where this trial is running

London, London, City of

• Hammersmith Hospital — London, London, City of, United Kingdom (Recruiting)

Study contacts

• Principal investigator: Rohini Sharma, Professor — Imperial College London
• Study coordinator: Rohini Sharma, Professor

Conditions Neuroendocrine Tumors