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Lutathera and ASTX727 in Neuroendocrine Tumours (LANTana)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05178693
Recruitment Status : Not yet recruiting
First Posted : January 5, 2022
Last Update Posted : January 5, 2022
Sponsor:
Collaborator:
Advanced Accelerator Applications, a Novartis company
Information provided by (Responsible Party):
Imperial College London

Brief Summary:
Patients entered into the study will receive ASTX727 orally up to 3 to 8 days prior to receiving Lutathera treatment 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.

Condition or disease Intervention/treatment Phase
Neuroendocrine Tumors Drug: ASTX727 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 27 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Epigenetic Modification of Somatostatin Receptor-2 to Improve Therapeutic Outcome With Lutathera in Patients With Metastatic Neuroendocrine Tumours.
Estimated Study Start Date : January 10, 2022
Estimated Primary Completion Date : December 31, 2025
Estimated Study Completion Date : December 31, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment Drug: ASTX727
Cedazuridine 100mg + 35mg decitabine




Primary Outcome Measures :
  1. 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 [ Time Frame: Through study completion, an average of 1 year ]
    This outcome will be assessed using a specific PET scan


Secondary Outcome Measures :
  1. To assess tolerability of combination therapy [ Time Frame: Through study completion, an average of 1 year ]
    This outcome will be assessed using CTCAE v5.0

  2. To assess response to treatment using conventional imaging [ Time Frame: Through study completion, an average of 1 year ]
    This outcome will be assessed using standard of care CT scans

  3. To assess patients quality of life during treatment [ Time Frame: Through study completion, an average of 1 year ]
    This will be assessed using standardised quality of life questionnaires, which will be given to the patients

  4. To assess progression free survival [ Time Frame: Through study completion, an average of 1 year ]
    This will be the time until patients show progressive disease on their routine CT scans



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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. histologically or cytologically confirmed diagnosis of neuroendocrine tumour
  4. archival tissue block available
  5. 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 Version 3.6 - 4th Novermber 2021 IRAS ID 285903 Page 11 of 69
  8. ECOG Performance status 0 - 2
  9. Tumoural uptake on [68Ga]-DOTA-TATE greater 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 (see table 4)
  12. Women of childbearing potential must be willing to use a highly effective method of contraception as outlined in Appendix 4 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 Appendix 4 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 Version 3.6 - 4th Novermber 2021 IRAS ID 285903 Page 12 of 69 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05178693


Contacts
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Contact: Rohini Sharma, MD 02083833170 rohini.sharma2@nhs.net

Sponsors and Collaborators
Imperial College London
Advanced Accelerator Applications, a Novartis company
Investigators
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Principal Investigator: Rohini Sharma, MD Imperial College London
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Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT05178693    
Other Study ID Numbers: RS - IC03
First Posted: January 5, 2022    Key Record Dates
Last Update Posted: January 5, 2022
Last Verified: December 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue