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Comparing two dosing schedules of Lutetium‑177 Dotatate for slowly progressive midgut neuroendocrine tumors

Randomized Interval Assessment Trial of Lu177-Dotatate Every 8 Versus Every 16 Weeks in Slowly Progressive G1-2 Advanced Midgut Neuroendocrine Tumors (NETs) to Lower TOxicity

Phase 3 Interventional Grupo Espanol de Tumores Neuroendocrinos · NCT06878664

This will test whether giving Lu‑177 Dotatate every 16 weeks instead of every 8 weeks works as well but causes fewer blood-related side effects for people with slowly progressive, Grade 1–2 midgut neuroendocrine tumors that are somatostatin receptor–positive.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment166 (estimated)
Ages18 Years and up
SexAll
SponsorGrupo Espanol de Tumores Neuroendocrinos Academic / other
Drugs / interventionsradiation
Locations21 sites (Caen, Caen and 20 other locations)
Trial IDNCT06878664 on ClinicalTrials.gov

What this trial studies

This randomized Phase III de‑escalation study will enroll about 166 patients with unresectable or metastatic, slowly progressive, well‑differentiated Grade 1–2 midgut neuroendocrine tumors that are somatostatin receptor positive. Participants are randomized to receive four cycles of 7.4 GBq Lu‑177 Dotatate given either every 8 weeks (standard) or every 16 weeks (less intensive), with concomitant somatostatin analog therapy and amino acid protection. The primary objective is to show that the 16‑week schedule causes less serious hematologic toxicity, while secondary objectives include comparing clinical, hormonal and radiologic responses, progression‑free and overall survival, and rates of clonal hematopoiesis and therapy‑related myeloid neoplasms. Safety, duration of grade ≥2 hematologic toxicity, overall toxicity, and exploratory predictors of efficacy and toxicity are also assessed.

Who should consider this trial

Good fit: Ideal candidates are adults with histologically confirmed, unresectable or metastatic, slowly progressive well‑differentiated Grade 1–2 midgut NETs (Ki‑67 ≤20%) with somatostatin receptor–positive disease who are candidates for Lu‑177 Dotatate and have had disease progression within the prior 36 months, without prior radioligand therapy.

Not a fit: Patients with high‑grade or rapidly progressive disease, somatostatin receptor–negative lesions, non‑midgut primary sites, prior peptide receptor radionuclide therapy, or who cannot tolerate somatostatin analogs are unlikely to benefit from this de‑escalation approach.

Why it matters

Potential benefit: If successful, patients could receive equally effective treatment with fewer severe blood‑related side effects and a lower risk of therapy‑related myeloid neoplasms.

How similar studies have performed: Previous randomized work (for example NETTER‑1) showed benefit using Lu‑177 Dotatate given every 8 weeks for midgut NETs, but comparing a 16‑week schedule to the standard 8‑week schedule is a novel question.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

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 lesions should also be somatostatin receptor positive in SSRT imaging (see guidance Appendix 10).
6. Measurable disease according to RECIST v1.1 criteria (Appendix 3)
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%; refer to Appendix 4) 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 last administration of 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:

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 history of 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%; refer to Appendix 4) 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.

Where this trial is running

Caen, Caen and 20 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Grade1-2 Advanced Midgut Neuroendocrine TumorsmidgutNeuroendocrine TumorsLu177-Dotatate
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.