Trial · Interventional
RecruitingPhase 3Registry dataRandomized Interval Assessment Trial of Lu177-Dotatate in Slowly Progressive G1-2 Advanced Midgut Neuroendocrine Tumors
Short name RIALTO
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
- Ph 3
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.
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)
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
Best radiological response
Time frame · 24 months
Registry description
Best radiological response according to local investigator RECIST V1.1
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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
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
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
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.
Number of RLT cycles per patient
Time frame · Throughout the study period, up to 24 month
Registry description
Number of RLT cycles per patient
Acumulative dose received each patient
Time frame · Throughout the study period up to 24 month
Registry description
Number acumulative dose received each patient
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
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