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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.
Accepts Healthy Volunteers
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms |
No |
Study Type
An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies. |
Interventional |
Eligible Ages | 18 Years and Over |
Gender | All |
Subjects must meet all the following criteria for enrollment in the study: 1. Histologically proven, Grade 1-2 well differentiated, inoperable, advanced GEP-NETs (Ki67 ≤20%) 2. Eastern Cooperative Oncology Group (ECOG) status 0-2. 3. Life expectancy of at least 12 weeks. 4. Subjects with functional tumors who are receiving SSAs on a stable dose for symptom control . Subjects that do not require octreotide LAR or lanreotide for symptom control must discontinue SSAs at least 4 weeks prior to randomization. 5. Progressive, SSTR-PET positive (i.e., Krenning score 3 or 4) GEP-NET (GI or pancreas) based on RECIST v1.1 following 2-4 cycles of treatment with 177Lu-labeled SSA. Must have achieved disease control for at least 6 months following Lu-177 SSA. Radiographic progression must be demonstrated within 18 months of randomization. No time limit is defined between 177Lu-SSA treatment and randomization. Premature discontinuation of Lu-177 SSA treatment should not have been due to PD. 6. Part 2: Subject is a candidate for therapy with 1 of the following SoC options: 1. Everolimus 10 mg daily. 2. Sunitinib 37.5 mg daily. 3. High-dose octreotide LAR 60 mg Q4W. 4. High dose frequency lanreotide 120 mg every 2 weeks (Q2W) 7. Adequate renal function, as evidenced by creatinine clearance (CrCl) ≥60 mL/min (calculated using the Cockcroft-Gault formula) (Cockcroft and Gault, 1976) 8. Adequate hematologic function, defined by the following laboratory results: 1. Part 1: Hemoglobin concentration ≥5.6 mmol/L (≥9.0 g/dL); absolute neutrophil count (ANC) ≥1500 cells/µL (≥1500 cells/mm3); platelets ≥100 x 109/L (100 x 103/mm3) 2. 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). 9. Total bilirubin ≤3 x upper limit normal (ULN) 10. Serum albumin ≥3.0 g/dL unless prothrombin time is within the normal range. 11. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 48 hours prior to the first dose of study drug and agree to use barrier contraception and a second form of highly effective contraception (Clinical Trials Facilitation Group [CTFG] 2014) or total abstinence while receiving study drug and for 6 months following their last dose of RYZ101. 12. Sexually active male subjects must use a condom during intercourse while receiving study drug and for 3 months after the last dose of the study drug and should not father a child during this period. If sexual partners are WOCBP must also agree to use a second form of highly effective contraception (CTFG 2014) or total abstinence while receiving study drug and for 3 months following their last dose of RYZ101. 13. Able to read and/or understand the details of the study and provide written informed consent prior to any study-specific assessments and procedures commence. Subjects who meet any of the following criteria will be excluded from the study: 1. Known hypersensitivity to 225Actinium, 68Gallium, 64Copper, octreotate, or any of the excipients of DOTATATE imaging agents. 2. Part 1: Prior treatment with alkylating agents. 3. Prior radioembolization. 4. Any surgery, chemoembolization, and radiofrequency ablation within 12 weeks prior to first dose of study drug. 5. Use of anticancer agents within the following intervals prior to the first dose of study drug: 1. PRRT: within <6 months. 2. Chemotherapy: within <6 weeks. 3. Small molecule inhibitors: within <4 weeks. 4. Biological agents: within 4 weeks. 6. Prior external-beam radiation (EBRT) therapy as defined below: 1. Part 1: Any prior EBRT, including SBRT. 2. Part 2: Prior EBRT within 6 weeks prior to study enrollment or any prior EBRT to more than 25% of the bone marrow. 7. Prior participation in any interventional clinical study within 30 days prior to first dose of study drug. 8. Current somatic or psychiatric disease/condition that may interfere with the objectives and assessments of the study. 9. 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. 10. 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) 11. Uncontrolled diabetes mellitus as defined by hemoglobin A1C (HgB A1C) ≥8% 12. Have a history of primary malignancy within the past 3 years other than
Trial ID:
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries. |
NCT05477576 |
Phase
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use. |
Phase 3 |
Lead Sponsor
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data. |
RayzeBio, Inc. |
Principal Investigator
The person who is responsible for the scientific and technical direction of the entire clinical study. |
Denis Ferreira, MD |
Principal Investigator Affiliation | RayzeBio Sr. Medical Director |
Agency Class
Category of organization(s) involved as sponsor (and collaborator) supporting the trial. |
Industry |
Overall Status | Recruiting |
Countries | Belgium, Brazil, Canada, France, Netherlands, Spain, United States |
Conditions
The disease, disorder, syndrome, illness, or injury that is being studied. |
GEP-NET, Gastroenteropancreatic Neuroendocrine Tumor, Gastroenteropancreatic Neuroendocrine Tumor Disease, Neuroendocrine Tumors, Carcinoid, Carcinoid Tumor, Pancreatic NET |
Experimental: Phase 1b - RYZ101
Part 1 is an uncontrolled dose de-escalation study to confirm the safety and determine the RP3D of RYZ101 based on Bayesian optimal interval design. Eligible participants will be enrolled in cohorts of 6 to receive RYZ101 up to 4 infusions every 8 weeks. If the initial dose level is not tolerated, the dose will be de-escalated; up to 3 dose levels will be assessed.
Active Comparator: Phase 3 - RYZ101
Actinium 225 radiolabeled somatostatin analog (SSA) for injection
Active Comparator: Phase 3 - Standard of Care
Investigator's choice of standard of care between everolimus, sunitinib, octreotide, or lanreotide.
Drug: - RYZ101
RP3D as determined in Phase 1b
Drug: - Everolimus 10 mg
Everolimus 10 mg daily by mouth
Drug: - Sunitinib 37.5 MG
Sunitinib 37.5 mg daily by mouth
Drug: - Octreotide LAR 60 MG Injection
High-dose octreotide LAR 60 mg Q4W by i.m. injection
Drug: - Lanreotide 120Mg Sa Susp Inj Syringe
High dose frequency lanreotide 120 mg Q2W by deep s.c. injection
If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.
Status
Recruiting
Address
University of California, San Francisco
San Francisco, California, 94143
Status
Recruiting
Address
Yale Cancer Center
New Haven, Connecticut, 06510
Status
Recruiting
Address
MedStar Washington Hospital Center
Washington, District of Columbia, 20010
Status
Recruiting
Address
Mayo Clinic Florida
Jacksonville, Florida, 32224
Status
Recruiting
Address
Biogenix Molecular
Miami, Florida, 33165
Status
Recruiting
Address
Moffitt Cancer Center
Tampa, Florida, 33607
Status
Recruiting
Address
Winship Cancer Institute, Emory University Hospital Midtown
Atlanta, Georgia, 30322
Status
Recruiting
Address
University of Iowa Hospitals & Clinics
Iowa City, Iowa, 52242
Status
Recruiting
Address
University of Kentucky Markey Cancer Center
Lexington, Kentucky, 40536
Status
Recruiting
Address
Advanced Molecular Imaging and Therapy
Glen Burnie, Maryland, 21061
Status
Recruiting
Address
Boston Medical Center
Boston, Massachusetts, 02118
Status
Recruiting
Address
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Status
Recruiting
Address
Profound Research LLC/MHP Radiation Oncology Institute
Troy, Michigan, 48098
Status
Recruiting
Address
Mayo Clinic Rochester
Rochester, Minnesota, 55905
Status
Recruiting
Address
Washington University - St. Louis
Saint Louis, Missouri, 63110
Status
Recruiting
Address
Nebraska Cancer Specialists
Omaha, Nebraska, 68130
Status
Recruiting
Address
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
Status
Recruiting
Address
Memorial Sloan Kettering
New York, New York, 10065
Status
Recruiting
Address
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
Status
Recruiting
Address
Oregon Health & Science University
Portland, Oregon, 97239
Status
Recruiting
Address
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Status
Recruiting
Address
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Status
Recruiting
Address
Mayo Clinic Arizona
Phoenix, Arizona, 85054
Status
Recruiting
Address
City of Hope
Duarte, California, 91010
Status
Recruiting
Address
UCLA Nuclear Medicine
Los Angeles, California, 90095
Status
Recruiting
Address
Hoag Memorial Hospital Presbyterian
Newport Beach, California, 92663
Status
Not yet recruiting
Address
Stanford University
Palo Alto, California, 94305
Status
Recruiting
Address
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
Status
Recruiting
Address
MD Anderson
Houston, Texas, 77030
Status
Recruiting
Address
Huntsman Cancer Hospital University of Utah
Salt Lake City, Utah, 84112
Status
Recruiting
Address
Fred Hutchinson Cancer Center
Seattle, Washington, 98109
Status
Recruiting
Address
Institut Jules Bordet
Brussels, ,
Status
Recruiting
Address
Cliniques universitaires Saint-Luc
Brussel, ,
Status
Not yet recruiting
Address
UZ Leuven
Leuven, ,
Status
Recruiting
Address
AZ Delta
Roeselare, ,
Status
Recruiting
Address
Sociedade Beneficente De Senhoras Hospital - Sírio-Libanês Brasilia
Brasília, ,
Status
Not yet recruiting
Address
Instituto D'or de Pesquisa e Ensino
Rio De Janeiro, ,
Status
Not yet recruiting
Address
Instituto Nacional de Cancer
Rio De Janeiro, ,
Status
Not yet recruiting
Address
Fundacao Antonio Prudente - A.C. Camargo Cancer Center
São Paulo, ,
Status
Not yet recruiting
Address
Hospital Israelita Albert Einstein
São Paulo, ,
Status
Recruiting
Address
Sociedade Beneficente de Senhoras Hospital Sirio-Libanes
São Paulo, ,
Status
Recruiting
Address
London Health Sciences Centre
London, Ontario,
Status
Recruiting
Address
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5
Status
Recruiting
Address
Jewish General Hospital
Montréal, Quebec,
Status
Not yet recruiting
Address
University Health Network - Princess Margaret Cancer Centre
Toronto, ,
Status
Not yet recruiting
Address
CHU Beaujon, APHP.Nord - Université Paris Cité
Clichy, ,
Status
Not yet recruiting
Address
CHRU de Lile
Lille, ,
Status
Recruiting
Address
CHU De Nantes
Nantes, ,
Status
Not yet recruiting
Address
CHRU de Nancy Hôpital de Brabois
Vandoeuvre-Lès-Nancy, ,
Status
Not yet recruiting
Address
Institut Gustave Roussy
Villejuif, ,
Status
Recruiting
Address
UMC Utrecht
Utrecht, ,
Status
Not yet recruiting
Address
Hospital Universitari Vall d'Hebron
Barcelona, ,
Status
Not yet recruiting
Address
Hospital HM Universitario Sanchinarro
Madrid, ,
Status
Not yet recruiting
Address
Hospital Universitario 12 de Octubre
Madrid, ,
Status
Not yet recruiting
Address
Hospital Universitario La Paz
Madrid, ,
Status
Not yet recruiting
Address
Hospital Universitario Ramon Y Cajal
Madrid, ,
Status
Not yet recruiting
Address
MD Anderson Cancer Center
Madrid, ,
Status
Not yet recruiting
Address
Hospital Universitario Miguel Servet
Zaragoza, ,