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Recruiting NCT05477576

Study of RYZ101 Compared With SOC in Pts w Inoperable SSTR+ Well-differentiated GEP-NET That Has Progressed Following 177Lu-SSA Therapy

Phase III Interventional GEP-NET Gastroenteropancreatic Neuroendocrine Tumor Gastroenteropancreatic Neuroendocrine Tumor Disease Neuroendocrine Tumors

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: RYZ101, Everolimus, Sunitinib, Octreotide.
Who it may be relevant to
Registry conditions: GEP-NET, Gastroenteropancreatic Neuroendocrine Tumor, Gastroenteropancreatic Neuroendocrine Tumor Disease, Neuroendocrine Tumors. Basic parameters: from 18 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United States, Belgium, Brazil, Canada, France +3
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

Phase 1b/3 Global, Randomized, Controlled, Open-label Trial Comparing Treatment With RYZ101 to Standard of Care Therapy in Subjects With Inoperable, Advanced, SSTR+, Well-differentiated GEP-NETs That Have Progressed Following Prior 177Lu-SSA Therapy

Overview

This study aims to determine the safety, pharmacokinetics (PK) and recommended Phase 3 dose (RP3D) of RYZ101 in Part 1, and the safety, efficacy, and PK of RYZ101 compared with investigator-selected standard of care (SoC) therapy in Part 2 in subjects with inoperable, advanced, well-differentiated, somatostatin receptor expressing (SSTR+) gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that have progressed following treatment with Lutetium 177-labelled somatostatin analogue (177Lu-SSA) therapy, such as 177Lu-DOTATATE or 177Lu-DOTATOC (177Lu-DOTATATE/TOC), or 177Lu-high affinity \[HA\]-DOTATATE.

Interventions

  • Drug RYZ101
    RP3D as determined in Phase 1b
  • Drug Everolimus
    Everolimus
  • Drug Sunitinib
    Sunitinib
  • Drug Octreotide
    High-dose octreotide
  • Drug Lanreotide
    Lanreotide

Primary outcome measures

  • Phase 1b: RP3D [Time frame: 56 days of study treatment]
  • Phase 3: PFS as determined by BICR [Time frame: After the target number of 143 PFS events have occurred]

Eligibility criteria

Inclusion:

  • Histologically proven, Grade 1-2 well differentiated, inoperable, advanced GEP-NETs (Ki67 ≤20%) Eastern Cooperative Oncology Group (ECOG) status 0-2. Ki67% <20% is not required for the ad hoc subcohort of the PK/ECG substudy.
  • Progressive, SSTR-PET positive (i.e., Krenning score 3 or 4) GEP-NET (GI or pancreas) following 2-4 cycles of treatment with 177Lu-labeled SSA. Must have achieved disease control for at least 6 months following Lu-177 SSA (archival tissue is not required for the ad hoc subcohort of the PK/ECG substudy). No time limit is defined between 177Lu-SSA treatment and randomization. There must be at least 1 SSTR-PET imaging-positive measurable site of disease (according to RECIST v1.1) and no RECIST v1.1 measurable metastatic lesions that are SSTR imaging-negative.
  • Adequate renal function, as evidenced by estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 (calculated using the Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\]) (Levey et al. 2009)
  • Adequate hematologic function, defined by the following laboratory results:
  • Part 2: Hemoglobin concentration ≥5.0 mmol/L (≥8.0 g/dL); ANC ≥1000 cells/µL (≥1000 cells/mm3); platelets ≥75 x 109/L (75 x 103/mm3).
  • Total bilirubin ≤3 x upper limit normal (ULN)
  • Serum albumin ≥3.0 g/dL unless prothrombin time is within the normal range

Exclusion:

  • Prior radioembolization
  • Significant cardiovascular disease, such as New York Heart Association (NYHA) Class ≥II heart failure, left ventricular ejection fraction (LVEF) <40% or QT interval corrected for heart rate using Fridericia's formula (QTcF) >450 ms for males and >470 ms for females.
  • Resistant hypertension, defined as uncontrolled blood pressure (BP) >140/90 mmHg while on optimal doses of at least 3 antihypertensive medications with 1 being a diuretic (Whelton et al. 2018)
  • Uncontrolled diabetes mellitus as defined by hemoglobin A1C (HgB A1C) ≥8%
  • PRRT other than Lu-177 SSA (not applicable for ad hoc subcohort of the PK/ECG substudy)
  • Any condition requiring systemic treatment with high-dose glucocorticoids within 14 days prior to first dose of study treatment and/or which cannot be stopped while on study. Inhaled or topical steroids are permitted.
  • Prior history of liver cirrhosis or liver transplantation

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Parallel assignment
Masking
Open label
Primary purpose
Treatment

Study locations

United States · 32 centers
  • Research Facility — Phoenix
  • Research Facility — Duarte
  • Research Facility — Irvine
  • Research Facility — Los Angeles
  • Research Facility — Palo Alto
  • Research Facility — San Francisco
  • Research Facility — New Haven
  • Research Facility — Washington D.C.
  • … and 24 more centers
France · 6 centers
  • Research Facility — Clichy
  • Research Facility — Lille
  • Research Facility — Montpellier
  • Research Facility — Nantes
  • Research Facility — Vandœuvre-lès-Nancy
  • Research Facility — Villejuif
Belgium · 3 centers
  • Research Facility — Brussels
  • Research Facility — Leuven
  • Research Facility — Roeselare
Brazil · 3 centers
  • Research Facility — Brasília
  • Research Facility — Rio de Janeiro
  • Research Facility — São Paulo
Canada · 3 centers
  • Research Facility — London
  • Research Facility — Toronto
  • Research Facility — Montreal
Netherlands · 3 centers
  • Research Facility — Amsterdam
  • Research Facility — Maastricht
  • Research Facility — Utrecht
Spain · 3 centers
  • Research Facility — Barcelona
  • Research Facility — Madrid
  • Research Facility — Zaragoza
South Korea · 1 center
  • Research Facility — Seoul

Publications

  • Taunk NK, Escorcia FE, Lewis JS, Bodei L. Radiopharmaceuticals for Cancer Diagnosis and Therapy: New Targets, New Therapies-Alpha-Emitters, Novel Targets. Cancer J. 2024 May-Jun 01;30(3):218-223. doi: 10.1097/PPO.0000000000000720. PMID 38753757

Identifiers

NCT: NCT05477576 · RYZ101-301

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗