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Trial · Interventional

RecruitingPhase 3Registry data

Randomized Interval Assessment Trial of Lu177-Dotatate in Slowly Progressive G1-2 Advanced Midgut Neuroendocrine Tumors

Short name RIALTO

NCTNCT06878664 (opens ClinicalTrials.gov in a new tab)Other idRLTTio2023 / GETNE T2421Other id2024-517921-14-00

Overview

Status
Recruiting
Phase
Phase 3
Enrollment
166 participants (estimated)
Sponsor
Grupo Espanol de Tumores Neuroendocrinos · Other
Design
Randomized · Single masking
Countries
2 countries

France, Spain

Start
12 Jun 2025
Primary completion
Jan 2029 (estimated)
Completion
Jan 2029 (estimated)
First posted
17 Mar 2025
Last update posted
16 Sept 2026
Conditions
Grade1-2 Advanced Midgut Neuroendocrine Tumors (NETs)

Timeline

1 trial · 1 ongoing

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
202520262027202820292030
  1. Ph 3

    RIALTO

    NCT06878664

    12 Jun 2025 to est. Jan 2029

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

This is a randomized Phase II/late phase I de-escalation clinical trial with approved investigational medicinal products in new use condition, low intervention. Disease under study Patients with unresectable or metastatic, slowly progressive, well-differentiated (Grade1 and Grade2), somatostatin receptor-positive midgut neuroendocrine tumors (GEP-NETs). It is planned to randomize 166 patients with a histologically confirmed diagnosis of slowly progressive grade 1 or grade 2 advanced midgut neuroendocrine tumors (NETs) candidates to receive 177Lu-Dotatate targeted radioligand therapy (RLT). Patients are required to have SSTR+ disease, as evidenced on somatostatin receptor imaging. Patients will be randomized into two arms: 1. control arm: regimen 177Lu-Dotatate every 8 weeks (q8w) 2. experimental arm: regimen 177Lu-Dotatate every 16 weeks (q16w) Research hypothesis: Less intensive somatostatin-receptor (SST) targeted radioligand therapy (RLT) (7.4 GBq/cycle 177Lu-Dotatate every 16 weeks x 4 cycles) is associated with less severe hematological toxicities and may mitigate the risk to develop therapy-related myeloid neoplasms (t-MN) with similar antitumor efficacy in slowly growing gastrointestinal grade 1-2 NETs.

Interventions

  • 177Lu-Dotatate (7.4 Gigabecquerel/cycle) during 30 min intravenous infusion every 16 weeks (q8w) x 4 cycles; 2) and 3) as in the experimental arm.Drug
  • 177Lu-Dotatate (7.4 Gigabecquerel/cycle) during 30 min intravenous infusion every 8 weeks (q8w) x 4 cycles; 2) and 3) as in the experimental arm.Drug
  • Amino acid solutionDrug
  • Lanreotide (Autogel formulation) or Octreotide LARDrug

Arms2

  • Experimental

    177Lu-Dotatate every 16 weeks

    Experimental arm: 1. Treatment with 177Lu-Dotatate (7.4 Gigabecquerel/cycle) during 30 min intravenous infusion every 16 weeks (q16w) x 4 cycles 2. Renal protection starting 30 minutes before targeted radioligand therapy (RLT) lasting 4 hours (iv amino acid solution of 14.4-20g of lysine and 14.9-20.7g of arginine in 1 to 2 liters of solution) 3. Long-acting standard doses of SSA (Lanreotide autogel 120 mg subcutaneous or Octreotide LAR 30 mg intramuscular, starting 24h after RLT every 4 weeks during RLT (q16w interval SSA administration should be adjusted to RLT administrations so that SSA is always given 24h after each RLT dose and at least 4 weeks prior to next RLT administration cycle) and q4w following last RLT administration until disease progression.

  • Active comparator

    177Lu-Dotatate every 8 weeks

    1. Treatment with 177Lu-Dotatate (7.4 Gigabecquerel/cycle) during 30 min intravenous infusion every 8 weeks (q8w) x 4 cycles 2. Renal protection starting 30 minutes before targeted radioligand therapy (RLT) lasting 4 hours (iv amino acid solution of 14.4-20g of lysine and 14.9-20.7g of arginine in 1 to 2 liters of solution); 3. Long-acting standard doses of SSA (Lanreotide autogel 120 mg subcutaneous or Octreotide LAR 30 mg intramuscular, starting 24h after RLT every 4 weeks during RLT (q8w interval SSA administration should be adjusted to RLT administrations so that SSA is always given 24h after each RLT dose and at least 4 weeks prior to next RLT administration cycle) and q4w following last RLT administration until disease progression

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Rate of Grade 2-5 hematological toxicity

    Time frame · Throughout the study period, from initiation of treatment with RLT up to 24 months

    Registry description

    The primary endpoint for the RIALTO trial is the frequency 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)

Secondary outcomes(20)
  1. Best hormonal response

    Time frame · 24 months

    Registry description

    Best hormonal response defined as greatest decrease, or \>30% decrease, of chromogranin A and 5HIAA from baseline if baseline levels were \>2x ULN or 5xULN

  2. Best radiological response

    Time frame · 24 months

    Registry description

    Best radiological response according to local investigator RECIST V1.1

  3. Duration of response (DoR)

    Time frame · Throughout the study period, from initiation of treatment with RLT up to 24 months

    Registry description

    Duration of response (DoR) according to local investigator RECIST v1.1. Time from first response (CR or PR), according to ORR definition for the trial, to the date of the documented PD as determined using RECIST v1.1 criteria or death due to any cause, whichever occurs first. Those patients with response and without PD or death event will be censored on the date of their last tumor assessment.

  4. Objective response rate (ORR)

    Time frame · Throughout the study period, from initiation of treatment with RLT up to 24 months

    Registry description

    Objective response rate (ORR) according to local investigator RECIST v1.1. Assessed by the investigator through imaging follow-up (CT scan/MRI) using RECIST v1.1 (Appendix 3). This will be considered as the percentage/proportion of randomized patients with complete response (CR) or partial response (PR) as their overall best response throughout the study period. The investigator will report the change in size of tumors as compared with baseline, before the first dose of study treatment.

  5. Disease control rate (DCR)

    Time frame · Throughout the study period, from initiation of treatment with RLT up to 24 months

    Registry description

    Disease control rate (DCR) RECIST v1.1 according to local investigator RECIST v1.1. Assessed by the investigator through imaging follow-up (CT scan/MRI) using RECIST v1.1. This will be considered as the percentage/proportion of randomized patients with complete response (CR) or partial response (PR) as their overall best response throughout the study period. The investigator will report the change in size of tumors as compared with baseline, before the first dose of study treatment.

  6. Progression-free survival (PFS)

    Time frame · Throughout the study period, up to 3 months from radomization

    Registry description

    Progression-free survival (PFS) (investigator assessed) defined as the time between randomization date and disease progression according to RECIST v1.1 or death from any cause (primary analysis of PFS) .PFS will be censored at the date of the last adequate tumor assessment if no PFS event is observed prior to the analysis cut-off date.

  7. Progression-free survival (PFS)

    Time frame · Throughout the study period, up to 12 months from radomization

    Registry description

    Progression-free survival (PFS) (investigator assessed) defined as the time between randomization date and disease progression according to RECIST v1.1 or death from any cause (primary analysis of PFS). PFS will be censored at the date of the last adequate tumor assessment if no PFS event is observed prior to the analysis cut-off date.

  8. Progression-free survival (PFS)

    Time frame · Throughout the study period, up to 24 months from radomization

    Registry description

    Progression-free survival (PFS) (investigator assessed) defined as the time between randomization date and disease progression according to RECIST v1.1 or death from any cause (primary analysis of PFS) .PFS will be censored at the date of the last adequate tumor assessment if no PFS event is observed prior to the analysis cut-off date.

  9. Overall survival

    Time frame · Throughout the study period, up to 6 months from radomization

    Registry description

    Overall survival defined as the time elapsed from randomization until death from any cause. Patients alive and free of events at the date of the analysis will be censored at their last known contact.

  10. Overall survival

    Time frame · Throughout the study period, up to 12 months from radomization

    Registry description

    Overall survival defined as the time elapsed from randomization until death from any cause. Patients alive and free of events at the date of the analysis will be censored at their last known contact.

  11. Overall survival

    Time frame · Throughout the study period, up to 18 months from radomization

    Registry description

    Overall survival defined as the time elapsed from randomization until death from any cause. Patients alive and free of events at the date of the analysis will be censored at their last known contact.

  12. Overall survival

    Time frame · Throughout the study period, up to 24 months from radomitation

    Registry description

    Overall survival defined as the time elapsed from randomization until death from any cause. Patients alive and free of events at the date of the analysis will be censored at their last known contact.

  13. Worst grade non-hematological toxicity per patient

    Time frame · Throughout the study period, up to 24 months

    Registry description

    Percentage of patients with Non-hematological toxicity. Non-hematological toxicity: defined as worst grade non-hematological toxicity per patient according to NCI-CTCAE v 5.0 criteria.

  14. Rate of clonal hematopoiesis

    Time frame · Throughout the study period, at baseline

    Registry description

    Rate of clonal hematopoiesis by Next-Generation Sequencing (NGS) of ctDNA calculated by mutations frequency in ctDNA samples

  15. Rate of clonal hematopoiesis

    Time frame · Throughout the study period, up to 3 months from the start of treatment of the study

    Registry description

    Rate of clonal hematopoiesis by Next-Generation Sequencing (NGS) of ctDNA calculated by mutations frequency in ctDNA

  16. Rate of clonal hematopoiesis

    Time frame · Throughout the study period, up to 12 months from the start of treatment of the study

    Registry description

    Rate of clonal hematopoiesis by Next-Generation Sequencing (NGS) of ctDNA calculated by mutations frequency in ctDNA samples

  17. Rate of clonal hematopoiesis

    Time frame · Throughout the study period, up to 24 months from the start of treatment of the study

    Registry description

    Rate of clonal hematopoiesis by Next-Generation Sequencing (NGS) of ctDNA calculated by mutations frequency in ctDNA samples.

  18. Number of RLT cycles per patient

    Time frame · Throughout the study period, up to 24 month

    Registry description

    Number of RLT cycles per patient

  19. Acumulative dose received each patient

    Time frame · Throughout the study period up to 24 month

    Registry description

    Number acumulative dose received each patient

  20. Treatment compliance analyzing treatment delays and interruptions due to toxicity

    Time frame · Throughout the study period, time from first to last RLT dose

    Registry description

    Treatment compliance analyzing treatment delays and interruptions due to toxicity, rate of patients completing planned schedule, time from first to last RLT dose

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

No results are posted for this trial.

A trial that is still running, or that stopped early, may post results later.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
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.

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