Clinical trial • Phase III • Oncology

DOTATATE; Lutetium-177; Yttrium-90 for Gastrointestinal neuroendocrine tumour

Phase III trial of DOTATATE; Lutetium-177; Yttrium-90 for Gastrointestinal neuroendocrine tumour.

Overview

Trial Therapeutic Area
Oncology
Trial Disease
Gastrointestinal neuroendocrine tumour
Trial Stage
Phase III
Drug Modality
Radiopharmaceutical

Key dates

Initial CTIS Submission Date
15-11-2024
First CTIS Authorization Date
11-01-2025

Trial design

Randomised, open-label, group a: [177lu]lu-dota-tate fixed dose of 7400 mbq radioactivity (standard arm). group b: [177lu]lu-dota-tate with [90y]y-dota-tate - initially in a ratio of 3700:1850 mbq/mbq; ratio individually adjusted in subsequent cycles based on imaging, pharmacokinetics and calculated absorbed doses. group c: [177lu]lu-dota-tate with [90y]y-dota-tate - initially in a ratio of 3700:1850 mbq (individualized selection of ratio with fixed 90y or 177lu as described). group d: [177lu]lu-dota-tate initially 7400 mbq then individualized dose based on imaging/pharmacokinetics/dosimetry.-controlled, adaptive Phase III trial in Poland.

Randomised
Yes
Open Label
Yes
Comparator
Group A: [177Lu]Lu-DOTA-TATE fixed dose of 7400 MBq radioactivity (standard arm). Group B: [177Lu]Lu-DOTA-TATE with [90Y]Y-DOTA-TATE - initially in a ratio of 3700:1850 MBq/MBq; ratio individually adjusted in subsequent cycles based on imaging, pharmacokinetics and calculated absorbed doses. Group C: [177Lu]Lu-DOTA-TATE with [90Y]Y-DOTA-TATE - initially in a ratio of 3700:1850 MBq (individualized selection of ratio with fixed 90Y or 177Lu as described). Group D: [177Lu]Lu-DOTA-TATE initially 7400 MBq then individualized dose based on imaging/pharmacokinetics/dosimetry.
Adaptive
True - several arms include individualized adjustment of the 177Lu:90Y ratio or individualized dosing based on imaging studies, pharmacokinetics and calculated absorbed doses in tumour, kidney and bone marrow; these constitute adaptive dose-selection rules across cycles.
Single Multiple Or Escalation Dose Combined
Yes
Target Sample Size
92
Trial Duration For Participant
1825

Eligibility

Recruits 92 No vulnerable populations are selected. Only adults (Age over 18 years) are eligible; age under 18 is an exclusion. Participants lacking capacity to give informed consent are excluded. Written informed consent must be signed by the participant (no provision for proxy consent or assent described)..

Pregnancy Exclusion
Pregnancy or breastfeeding.
Vulnerable Population
No vulnerable populations are selected. Only adults (Age over 18 years) are eligible; age under 18 is an exclusion. Participants lacking capacity to give informed consent are excluded. Written informed consent must be signed by the participant (no provision for proxy consent or assent described).

Inclusion criteria

  • {"criterion_text":"- Associated with neuroendocrine tumour: a)Presence of advanced, unresectable, histopathologically confirmed well and intermediate differentiated (G1 and G2) neuroendocrine tumour with high expression of somatostatin receptors on somatostatin receptor imaging (SRI) PET/CT with 68Ga-DOTA-TATE performed up to 12 weeks prior to first administration of therapy\n- Detection of tumour progression according to RECIST criteria 1. 1 on multiphasic CT or dynamic MR imaging within 18 months, with a qualifying study performed up to 12 weeks prior to the first administration of therapy\n- Laboratory tests*: ◦ Blood count with smear Hb > 9g/dl, platelets > 100,000/μl, leukocytes > 3,000/μl, neutrocytes > 1.5,000/μl, ◦ Creatinine <120 μmol/l (1.36 mg/dl) or eGFR>45 ml/min. ◦ ALT, AspAT, total bilirubin (values not exceeding 3x the reference standard) **it is acceptable to use for qualification the results of biochemical and haematological tests that are part of the medical history if they were performed up to 12 weeks before the qualifying visit and if, in the opinion of the investigator, there is no need and no indication to repeat them\n- Patient-related: Patient's overall Karnofsky score ≥60%.\n- Expected survival of more than 6 months.\n- Age over 18 years, with no upper age limit.\n- Ability to give informed consent to participate in the study.\n- Signing an informed consent form to participate in the study."}

Exclusion criteria

  • {"criterion_text":"- Cancer-related: Patient disability (Karnofsky <60)\n- Expected survival of less than 6 months.\n- Treatment for another malignancy less than 5 years prior to randomisation.\n- Associated with current and past medical therapies and interventions: PRRT in the past.\n- Chemotherapy or molecular treatment (for NEN or other cancer) in the past.\n- Patient-related: Age under 18 years.\n- Pregnancy or breastfeeding.\n- Patients with impaired bladder outflow or untreated urinary incontinence without catheter protection.\n- Lack of capacity to give informed consent to participate in the study.\n- Failure to sign an informed consent form to participate in the study."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Disease progression assessed by CT or MRI according to RECIST 1.1. Timepoints of Primary End Point evaluation: control imaging investigations (CT or MRI) using the technique identical with the one based on which the patient was qualified for the trial, performed after 3,6,12,24,36,49,60 months after completion of therapy with assessment according to RECIST 1.1","definition_or_measurement_approach":"Assessed by CT or MRI according to RECIST 1.1 at control imaging timepoints performed after 3, 6, 12, 24, 36, 49 and 60 months after completion of therapy (using the same imaging technique as the qualifying study)."}

Secondary endpoints

  • {"endpoint_text":"- Assessment of effectiveness and safety of personalized therapy. It is planned to perform biochemical tests during visit W1, during hospitalization and in the course of observation every 3 months (tests of blood morphology, urea, creatinine, eGFR, bilirubin). Total volume of blood collected at single timepoint - 6.8 ml.","definition_or_measurement_approach":"Effectiveness and safety assessed by biochemical tests at visit W1, during hospitalization and every 3 months during follow-up: blood morphology, urea, creatinine, eGFR, ALT, bilirubin; total blood drawn per timepoint 6.8 ml."}

Recruitment

Planned Sample Size
92
Recruitment Window Months
71
Consent Approach
Informed consent must be provided and signed by the participant; only adults (over 18) may consent. Lack of capacity to give informed consent is an exclusion. Subject information and informed consent form documents are included in the submission (ICF documents present). Language of public materials includes Polish (translations present). No specific remote/alternative consenting procedures described.

Geography

Total Number Of Sites
4
Total Number Of Participants
92

Poland

Earliest CTIS Part Ii Submission Date
05-12-2024
Latest Decision Or Authorization Date
27-03-2026
Processing Time Days
477
Number Of Sites
4
Number Of Participants
92

Sites

Site Name
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwersytecki W Krakowie
Department Name
Uniwersytet Jagielloński w Krakowie, Katedra i Klinika Endokrynologii
Contact Person Name
Alicja Hubalewska-Dydejczyk
Contact Person Email
alahub@cm-uj.krakow.pl
Site Name
Wojskowy Instytut Medyczny Panstwowy Instytut Badawczy
Department Name
Wojskowy Instytut Medyczny, Department of Endocrinology and Isotope Therapy
Contact Person Name
Grzegorz wiktor Kamiński
Contact Person Email
gkam@wim.mil.pl
Site Name
Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
Department Name
Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Instytut Badawczy
Contact Person Name
Marek Krzysztof Dedecjus
Contact Person Email
dyrektor@pib-nio.pl
Site Name
Swietokrzyskie Centrum Onkologii Samodzielny Publiczny Zaklad Opieki Zdrowotnej W Kielcach
Department Name
Świętokrzyskie Centrum Onkologii , Samodzielny Zakład Opieki Zdrowotnej, Dział Endokrynologii
Contact Person Name
Aldona Kowalska

Sponsor

Primary sponsor

Full Name
Narodowe Centrum Badan Jadrowych
Organisation Type
Laboratory/Research/Testing facility
Country Of Registered Address
Poland

Third parties

  • {"country":"Poland","full_name":"Genelytica Sp. z o.o.","duties_or_roles":"sponsorDuties codes: 1,5,6 (as listed in submission)","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
DuoNEN solution for injection
Active Substance
DOTATATE; Lutetium-177; Yttrium-90
Modality
Radiopharmaceutical
Routes Of Administration
Injection
Route
Injection
Starting Dose
7400 MBq (177Lu-DOTATATE fixed arm) ; initial mixture ratio 3700:1850 MBq (177Lu:90Y) for mixed arms
Dose Levels
Fixed 7400 MBq; Mixture initial ratio 3700:1850 MBq (177Lu:90Y); subsequent cycles individually adjusted based on imaging/pharmacokinetics/dosimetry
Maximum Dose
7.4 GBq
Dose Escalation Increase
Initial: 7400 MBq (or 3700:1850 MBq ratio for mixture arms); following doses individually adjusted (ratio or absolute activity changed) based on imaging studies, pharmacokinetics and calculated absorbed doses in tumour, kidney and bone marrow.
Combination Treatment
Yes

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