Neuroendocrine TumorsPhase 1LANTanaNCT05178693
Lutathera and ASTX727 in Neuroendocrine Tumours
A Phase 1 study testing ASTX727 and Lutathera in people with Neuroendocrine Tumors, run by Imperial College London at 1 site in United Kingdom.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Neuroendocrine Tumors
- What is being tested?
- ASTX727 and Lutathera
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 25 Apr 2022to 28 Feb 2029
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Be willing and able to provide written informed consent for the trial.
- Be aged 18 or over at the day of signing consent
- Histologic or cytologic confirmed diagnosis of neuroendocrine tumour
- Have archival tissue block available or willing to have fresh tissue biopsy if blocks not available
- Have disease that can be readily biopsied by ultrasound guidance (n=5)
- 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)
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- Progression or intolerance to first line therapy including somatostatin analogues
- ECOG Performance status 0 - 2
- No tumoural uptake on [68Ga]-DOTA-TATE or uptake less than background liver
- 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
- 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
- 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
Who cannot join
- Previous treatment with either study medication and/or known hypersensitivity to the study medication
- Serious concurrent medical illness, including serious active infection
- History of organ transplant
- Has a known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is required unless mandated by local health authority.
- Has a known history of active Bacillus Tuberculosis (TB).
- 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.
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- Bleeding or thrombotic disorders or subjects at risk for severe haemorrhage
- 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.
- 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.
- 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.
- 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 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
- Other clinically significant co-morbidities that could compromise the subject's participating in the study
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom1 site, 1 recruiting
- Recruiting
Hammersmith Hospital
London, London, City of, W12 0HS
Rohini Sharma, MD, 02075942807, rohini.sharma2@nhs.net
About this study
Official title: The Epigenetic Modification of Somatostatin Receptor-2 to Improve Therapeutic Outcome With Lutathera in Patients With Metastatic Neuroendocrine Tumours.
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.
Read the detailed description
Patients with neuroendocrine tumours (NET) who are found to be eligible will receive up to 4 doses of Lutathera on this trial. All participants will receive ASTX727 orally (cedazuridine 100mg + 35mg decitabine) Days 0-5 prior to receiving Lutathera Day 8 +/- 2days. Each cycle will be repeated every 2 months for 4 cycles unless unacceptable toxicity, progression of disease or withdrawal of patients' consent. Restaging will occur after 2 cycles of Lutathera and at the end of treatment. Patients will be followed 3 monthly until disease progression, death or withdrawal of patients' consent.
- Conditions
- Neuroendocrine Tumors
- Being tested
- ASTX727, Lutathera
- Medical subject headings
- Neuroendocrine Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ASTX727Drug
Cedazuridine 100mg + 35mg decitabine
LutatheraRadiation
Also called lutetium Lu 177 dotatate
Peptide receptor radionuclide therapy (PRRT)
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Not described Receives: Drug: ASTX727; Radiation: Lutathera |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine whether pre-treatment with ASTX727 results in re-expression of SSTR2 in patients with metastatic NETs, using [68Ga]-DOTA-TATE to image epigenetic modification of the SSTR2 locus allowing subsequent treatment with Lutathera
This outcome will be assessed using a specific PET scan
Measured: Through study completion, an average of 1 year
Secondary outcomes (4)
To assess tolerability of combination therapy
This outcome will be assessed using CTCAE v5.0
Measured: Through study completion, an average of 1 year
To assess response to treatment using conventional imaging
This outcome will be assessed using standard of care CT scans
Measured: Through study completion, an average of 1 year
To assess patients quality of life during treatment
This will be assessed using standardised quality of life questionnaires, which will be given to the patients
Measured: Through study completion, an average of 1 year
To assess progression free survival
This will be the time until patients show progressive disease on their routine CT scans
Measured: Through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2022
- Study start25 Apr 2022
- Primary completion30 Jun 2026 (estimated)
- Study completion28 Feb 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Neuroendocrine TumorsStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- Advanced Accelerator Applications
- Responsible party
- Sponsor
- Investigators
- Rohini Sharma, Professor, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05178693
- Sponsor's protocol ID
- RS - IC03
- Other IDs
- 21HH6544
- Acronym
- LANTana
- Status last verified
- Nov 2025
- First submitted
- 3 Dec 2021
- Last updated
- 24 Nov 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Murphy R, Chander G, Martinez M, Ward C, Khan SR, Naik M, Barwick T, Aboagye E, Sharma R. Study protocol of LANTana: a phase Ib study to investigate epigenetic modification of somatostatin receptor-2 with ASTX727 to improve therapeutic outcome with [177Lu]Lu-DOTA-TATE in patients with metastatic neuroendocrine tumours, UK. BMJ Open. 2023 Oct 24;13(10):e075221. doi: 10.1136/bmjopen-2023-075221.
PubMed 37879695