Lu177-Dotatate every 16 weeks to reduce adverse events in patients with midgut neuroendocrine tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Grupo Espanol De Tumores Neuroendocrinos

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

7 May 2025 → ongoing

Decision date (initial)

2025-03-20

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

GETNE

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Therapy, Efficacy

To demonstrate decreased serious hematological toxicity with a less intensive RLT regimen in slowly progressive advanced Grade 1-2 midgut NETs.

Secondary objectives 4

1. To show comparable efficacy (clinical, hormonal and radiological response, progression-free survival and overall survival) of the less intensive RLT regimen (cycles q16w) versus the conventional one (cycles q8w).
2. To compare the rate of clonal hematopoiesis among study arms (baseline and post-treatment) and assess its potential value to predict the risk of therapy-related myeloid neoplasms (t-MN).
3. To compare the duration of ≥ Grade 2 hematological toxicity (median and percentage rate of > 6 month duration)
4. To show decreased overall toxicity of the less intensive RLT regimen (cycles q16w) versus the conventional one (cycles q8w)

Conditions and MedDRA coding

Neuroendocrine tumors of midgut origin

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Patients who have histologically confirmed diagnosis of unresectable, advanced or metastatic midgut NETs (originated in the jejunum-ileum or right colon) who are candidates to receive 177Lu-Dotatate targeted radioligand therapy (RLT) and SSA. Patients with a large SRI+ mesenteric mass with abdominal-dominant disease judged by the investigator to be a midgut NET will also be eligible.
2. Ki-67 index ≤20%
3. Disease progression per RECIST v1.1 within 36 months prior to study entry.
4. Patients may be treatment naïve (first-line) or have received prior systemic therapy except for any type of prior RLT (not restricted to 177Lu-Dotatate).
5. In somatostatin receptor (SSTR) imaging all RECIST v1.1 evaluable target lesions and non-target lesions need to be SSTR positive (SSTR+) as defined by equal or above the liver uptake (this includes lesions of at least 10 mm in diameter in CT or MRI). If an FDG PET is performed (not mandatory), all FDG PET positive RECIST v1.1 lesions should also be somatostatin receptor positive in SSTR imaging
6. Measurable disease according to RECIST v1.1 criteria
7. Adequate organ function (hematological, renal and liver) based upon meeting all of the following laboratory criteria: Neutrophil count (ANC) ≥ 2,000/mm3. Platelet count ≥ 75 × 109/L. Hemoglobin ≥ 8 g/dL. Serum bilirubin ≤ 3.0 × upper limit of normal (ULN) or ≤ 3 × ULN for subjects with Gilbert’s disease. Serum albumin <3.0 g/dL unless prothrombin time is within the normal range. Creatinine clearance (CrCl) ≥ 50 mL/min as estimated by the Cockroft-Gault formula or as measured by 24-hour urine collection (GFR can also be used instead of CrCl). Note: renal tract obstruction is not allowed. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN or ≤ 5 xULN for subjects with liver metastases.
8. Karnofsky performance status (KPS) scale ≥ 70%.
9. Patient information and signing of the consent form, Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved, before any study-specific procedure. The patient must be able and willing to cooperate in monitoring study visits and procedures.
10. Patients ≥ 18 years of age.
11. Recovery to Grade ≤ 1 from any adverse event (AE) from prior treatment (excluding alopecia and/or asthenia).
12. Life expectancy ≥ 12 months.
13. Patients with health coverage (public or private), that includes coverage for patients enrolled in clinical trials, to both study treatments and determinations/procedures.
14. Female subject must provide a negative urine pregnancy test at screening, and must agree to use a medically accepted and highly effective birth control method (i.e. those with a failure rate less than 1%) for the duration of the study treatment and for 7 months after the final dose of study treatment. Sexually active men must agree to use the male condom during the study and until at least 7 months after the final administration of study treatment. Additionally, it is recommended that your female partner of childbearing age use a highly effective method of contraception.
15. Subject agrees not to participate in another interventional study while on treatment in the present study.

Exclusion criteria 13

1. Patients who have known hypersensitivity to lutetium-177 (177Lu), oxodotreotide, DOTA, somatostatin analogues, lysine, arginine, or any excipient/derivative of these agents.
2. Prior external beam radiation therapy (EBRT) to more than 25% of the bone marrow.
3. Prior whole liver internal radiation therapy (SIRT)
4. Prior radioligand therapy (RLT) (not restricted to 177Lu-Dotatate).
5. Prior major surgery, systemic therapy, embolization or other locoregional treatments within 4 weeks of study entry.
6. Patients who have a known active Hepatitis B (e.g., HBsAg reactive) or active hepatitis C (e.g., HCV RNA [qualitative] is detected). Patients who have a known active human immunodeficiency virus (HIV) infection (HIV 1 or 2).
7. Other known malignancies unless cured or definitively treated with no evidence of recurrence for 3 years.
8. Serious non-malignant disease (e.g. psychiatric, infectious, autoimmune, cardiovascular or dementia), that may interfere with the objectives of the trial or with the safety or compliance of the patient, as judged by the investigator.
9. Female patients must agree not to breastfeed or donate ovules starting at screening and throughout the study period, and for at least 7 months after the final study drug administration.
10. Male patients must agree not to donate sperm starting at screening and throughout the study period, and for at least 4 months after the final study drug administration.
11. Pregnancy or lactation. Men and women should not procreate during study treatment and until seven months after the final study drug administration.
12. For female patients of childbearing potential (defined as < 2 years after last menstruation and not surgically sterile) and male patients who are not surgically sterile and have female partners of childbearing potential that do not agree to use a medically accepted and highly effective birth control method (i.e. those with a failure rate less than 1%) for the duration of the study treatment and for 7 months after the final dose of study treatment.
13. Patient under guardianship or curatorship or deprived of liberty by a judicial or administrative decision or patient unable to give consent.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint for the RIALTO trial is the rate of Grade 2-5 hematological toxicity (worst per patient) from initiation of treatment with RLT up to 24 months thereafter according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5 (NCI-CTCAE v5)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Grupo Espanol De Tumores Neuroendocrinos

Sponsor organisation

Grupo Espanol De Tumores Neuroendocrinos

Address

Calle De Velazquez 7 Planta 3

City

Madrid

Postcode

28001

Country

Spain

Scientific contact point

Organisation

Grupo Espanol De Tumores Neuroendocrinos

Contact name

MFAR Clinical Research

Public contact point

Organisation

Grupo Espanol De Tumores Neuroendocrinos

Contact name

MFAR Clinical Research

Third parties 1

Locations

2 EU/EEA countries · 22 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 2 · Art. 52 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications