Neoplasms

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Blood and Lymph Conditions

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All Conditions

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Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Disease Progression

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

All Drugs and Chemicals

Somatostatin

Dose escalation study to assess the safety and determine the recommended phase II dose, based on time-to-event Bayesian optimal interval design, with a target toxicity rate of 30%. Three dose levels are planned to be evaluated: 5 MBq (starting dose), 7.5 MBq and 10 MBq (maximum dose allowed). The cohort size will be 3, with a maximum of 10 participants within a same dose level, and a maximum of 18 evaluable participants in total. Participants are planned to receive two cycles of intravenous infusion of 225Ac-DOTATATE every 6 weeks (Q6W). Each dose escalation and potential de-escalation step will be decided based on the dose-limiting toxicities (DLT) rate observed during the study treatment period (84 days following the first infusion), in the current dose cohort.

Two intravenous infusions every 6 weeks (Q6W)

225Ac-DOTATATE

Wendy Delbart, PhD

This study aims to determine the safety and the recommended phase II dose of RYZ101 (actinium-225 labelled DOTA-octreotate (225Ac-DOTATATE)) in participants with refractory and relapsing multiple myeloma (MM) that have received at least 3 prior lines of myeloma therapy. Participants will be selected based on somatostatin receptor (SSTR) positivity assessed by gallium-68 labelled DOTA-octreotate (68Ga-DOTATATE) PET/CT. The response to 225Ac-DOTATATE therapy will also be assessed in the target study population.

A Phase I Study to Assess the Tolerability of 225Ac-DOTATATE in Patients With Refractory and Relapsing Multiple Myeloma Expressing Somatostatin Receptors

Incidence and severity of adverse events (AEs) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0

Rate incidence of dose-limiting toxicities (DLT)

Overall response according to the International Myeloma Working Group (IMWG) response criteria

RayzeBio, Inc.

Jules Bordet Institute

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

Capecitabine

Fluorodeoxyglucose F18

Edotreotide

Edotreotide lutetium LU-177

Antimetabolites

Radiopharmaceuticals

Patients with 68Ga-DOTA- and 18F-FDG-PET-positive NET will receive a combination of intravenous 7.5 GBG (gigabequerel) 177Lu-DOTATOC for about 7 cycles in combination with capecitabine (4 cycles, cycle length 3 weeks, with one week without capecitabine, dosing 825 mg twice daily) and PRRT to a cumulative renal AD (absorbed dose) limit of 30 Gy and dosimetry-based PRRT.

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Intravenous infusion for about 7 treatment cycles with 7.5 GBq 177Lu-DOTATOC with an interval of 10 ± 2 weeks and PRRT to a cumulative renal AD limit of 30 Gy and dosimetry-based PRRT.

Standard treatment of 177Lu-DOTATOC with treatment for 4 cycles.

The investigational medicinal product (IMP) is 177Lu-DOTATOC which is registered as an orphan drug by the EMA ( European Medicines Agency) for the treatment of GEP-NEN (gastro-entero-pancreatic neuroendocrine tumor).

The IMP will be administered to participants both in the control arm and the experimental arms, but with different intervals, but the same activity; 7.5 Gbq per dosing.

177Lu-DOTATOC

Will be given orally with a dose of 825/m2 twice daily, starting on day 1 of each of the 4 first treatment cycles, cycle length 3 weeks.

There are several ways of personalizing PRRT (peptide receptor radionuclide treatment) in NEN (neuroendocrine neoplasia). Nevertheless, the current treatment regimen is not personalized. This trial aims to compare personalized PRRT to non-personalized PRRT in terms of safety, efficacy and resource demands in order to optimize treatment outcomes in an evidence-based manner in future.

This is a randomized, open-label, controlled trial in which patients are assigned to either non-personalized treatment with 4 cycles of 7.5 gigabequerel (GBq) 177Lu-DOTATOC (TOC), or personalized treatment based on dual imaging. In the personalized arm patients are treated according to the results of the dual imaging at screening:

A. Patients with 68Ga-1,4,7,10-tetra-azacyclododecane-N.n,N,N-tetraacetic acid (DOTA)-positron emission tomography (PET)-positive but 18F-2-fluoro-2-deoxy-D-glucosefluorodeoxyglucose (FDG)-PET-negative NET will receive dosimetry-based PRRT only (dTOC) B. Patients with 68Ga-DOTA- and 18F-FDG-PET-positive NET will receive a combination of capecitabine and dosimetry-based PRRT (CAP-dTOC).

Systemic Targeted Adaptive RadioTherapy of NeuroEndocrine Tumors.

Systemic Targeted Adaptive RadioTherapy of NeuroEndocrine Tumors. An Open-label, Multicenter, Randomized Phase III Trial Comparing Safety and Efficacy of Personalized Versus Non-personalized Radionuclide Therapy With 177Lu (Lutetium)-DOTATOC.

Time to progression is evaluated by CT (computed tomography) or MRI (magnetic resonance imaging) after every 16-22 weeks.

Time to progression is evaluated by CT (computed tomography) or MRI (magnetic resonance imaging) after every 10 +/- 2 weeks.

Treatment-related adverse reactions graded according to CTCAE v.5.0.

Median OS defined as time from randomization to death of any cause.

Percent change in SLD from baseline (within 4 weeks before treatment) to time of best response.

All patients complete the Eastern Cooperative Oncology Group (EORTC) QoL (quality of life)-questionnaires GI- neuroendocrine tumors (NET)21.

AD to target tumor lesions in subjects with complete remission (CR), partial remission (PR), stable disease (SD) and progressive disease (PD) as best response, according to RECIST evaluations.

Correlation between cumulative median absorbed dose to target tumor lesions and time to progression, defined as time from randomization to radiological progression.

Cumulative median AD and biological effective dose (BED) to kidneys vs rate of grade 3-4 renal toxicity (estimated and measured GFR ( glomerular filtration rate).

Differences in resource utilization and treatment cost between the two treatment arms, in relation to the progressive free survival (PFS) and overall survival (OS).

Lund University Hospital

Hypersensitivity

Recurrence

Control, age greater than or equal to 18 with normal renal function

Age 18 to less than 65 with mild renal impairment

Age 18 to less than 65 with moderate to severe renal impairment

Age 18 to less than 65 with end stage renal impairment

Age 65 to less than 75 with mild renal impairment

Age 65 to less than 75 with moderate to severe renal impairment

Age 65 to less than 75 with end stage renal impairment

Age greater than or equal to 75 with mild renal impairment

Age greater than or equal to 75 with moderate to severe renal impairment

Age greater than or equal to 75 with end stage renal impairment

Single intravenous injection of 222MBq (6.0 mCi) Indium In-111 pentetreotide

Indium In-111 pentetreotide

The objective of this study was to evaluate the effect of age (geriatric) and renal function on the safety, efficacy and pharmacokinetics of OctreoScan at the recommended clinical dose in this patient population.

Study to Evaluate the Effect of Age (Geriatric) and Kidney Function on the Safety, Efficacy and Pharmacokinetics of OctreoScan in Patients Who Have New or Recurrent Tumors

An Open-Label, Multi-Center, Phase 4 Study to Evaluate the Effect of Age (Geriatric) and Renal Function on the Safety, Efficacy (Sensitivity, Specificity) and Pharmacokinetics of OctreoScan in Patients Referred for Scintigraphy of All Solid Tumors With a High Suspicion of Containing Somatostatin Receptor Positive Tissue

Mallinckrodt

James Brodack, Ph.D.

Nervous System Diseases

Glioma

Central Nervous System Neoplasms

Medulloblastoma

Diffuse Intrinsic Pontine Glioma

Meningioma

Nervous System Neoplasms

Ependymoma

Disease Attributes

Neoplasms, Neuroepithelial

Neoplasms, Glandular and Epithelial

Neoplasms, Vascular Tissue

Meningeal Neoplasms

Brain Stem Neoplasms

Infratentorial Neoplasms

Brain Neoplasms

Brain Diseases

Central Nervous System Diseases

Anaplastic Ependymoma

Lutetium Lu 177 dotatate

Pediatric patients (4 -12 years, Phase I) and adolescent and young adult patients (\>12years, Phase II) with recurrent/progressive high-grade central nervous system tumors and meningiomas that express SST2A and demonstrate uptake on DOTATATE PET will receive Lutathera once every 8 weeks (1 cycle) for a total of 4 doses over 8 months

Phase I starting dose will be 200 mCi\*(BSA/1.73m2), corresponding to the BSA-adjusted FDA approved adult Lutathera dosing. The first cycle will be used as the DLT period. Once MTD/RP2D is established, an efficacy expansion cohort of up to 10 patients will be opened to determine the preliminary efficacy of MTD/RP2D of Lutathera in this cohort

Phase II patients will receive the adult RP2D of 200 mCi every 8 weeks to determine the anti-tumor activity of Lutathera in this patient population, through evaluation of 6-month PFS as the primary efficacy endpoint. Response will be assessed on imaging (brain/spine MRI and DOTATATE PET) following every cycle.

Lutathera: IV administration maximum dose of 200 mCi once every 8 weeks (one cycle) for total of 4 cycles (8 months)

LUTATHERA® (Lutetium Lu 177 dotatate)

Leonie Mikael

Kathleen Dorris, MD

Ashley Plant, MD

Susan Chi, MD

David H Ashley

Peter de Blank, MD

Margot Lazow, MD

Melinda Triplet

Michael J Fisher

Patricia Baxter, MD

Sarah Leary, MD

Margot Lazow

This study will evaluate the safety and efficacy of Lutathera (177Lu-DOTATATE) in patients with progressive or recurrent High-Grade Central Nervous System (CNS) tumors and meningiomas that demonstrate uptake on DOTATATE PET. The drug will be given intravenously once every 8 weeks for a total of up to 4 doses over 8 months in patients aged 4-12 years (Phase I) or older than 12 yrs (Phase II) to test its safety and efficacy, respectively.

Funding Source - FDA OOPD (grant number FD-R-0532-01)

Somatostatin receptors regulate cell growth through downstream modulation of both proliferation and apoptosis signaling pathways, and thus represent a potential therapeutic target. Lutathera (Lutetium \[Lu\]177 Dotatate) is a radionuclide therapy which binds type-2A somatostatin receptors (SST2A) and has recently gained FDA approval for the treatment of adult gastroenteropancreatic neuroendocrine tumors expressing SST2A.

High SST2A expression has been consistently observed in medulloblastoma and other embryonal tumors (75-100% of cases) as well as in some HGGs and anaplastic ependymomas (13-80%), with corresponding uptake on radiolabeled somatostatin receptor nuclear imaging (e.g. DOTATATE PET).

Emerging data has demonstrated treatment response (disease stabilization or regression) to somatostatin receptor-targeted therapy in children and young adults with relapsed medulloblastoma, HGG, meningioma, and brain metastases of neuroendocrine tumors, suggesting sufficient CNS penetration to achieve therapeutic benefit.

The proposed Phase I-II study will investigate the safety and efficacy of Lutathera treatment in patients whose tumors demonstrate uptake on DOTATATE PET (functional evidence of SST2A expression). In both Phase cohorts, Lutathera will be administered as an intravenous infusion on day 1 of each 8-week cycle for up to 4 cycles.

Phase I: (4-12 years) To determine the safety, define the dose-limiting toxicities, and establish the maximally tolerated dose (MTD)/ recommended Phase II dose (RP2D) of Lutathera in this patient population. The first cycle (first 8 weeks) will be used as the dose-limiting toxicity (DLT) observation period. The starting dose will be dose level 1, 200 mCi\*(body surface area \[BSA\]/1.73m2), which corresponds to the BSA-adjusted FDA approved adult dosing of Lutathera (200 mCi every 8 weeks). Once the MTD/RP2D is established, an efficacy expansion cohort of up to 10 patients will be opened to determine the preliminary efficacy of the MTD/RP2D of Lutathera in this cohort.

Phase II: (\>12 years) Enroll patients at the recommended adult dose of 200 mCi every 8 weeks to determine the anti-tumor activity of Lutathera at this dosing in this population. Response will be assessed on imaging (brain and/or spine MRI and DOTATATE PET) following every cycle.

Phase I (4-12 yrs) Lutathera (maximum dose of 200 mCi) once every 8 weeks (one cycle) for 4 cycles.

Level 0: 150 mCi\*(BSA/1.73m2). Level 1#: 200 mCi\*(BSA/1.73m2). Level 2: 250 mCi\*(BSA/1.73m2).

#starting dose

Phase II (\>12 yrs) RP2D 200 mCi once every 8 weeks

Lutathera for Treatment of Recurrent or Progressive High-Grade CNS Tumors

Phase I/II Study of Lutathera in Patients With Recurrent and/or Progressive High-Grade Central Nervous System Tumors and Meningiomas That Demonstrate Uptake on DOTATATE PET

Document anti-tumor activity of Lutathera through assessment of ORR, PFS in patients with recurrent or progressive High-Grade CNS tumors or meningiomas

Describe prevalence and heterogeneity of SST2A expression (IHC) in patients with recurrent or progressive High-Grade CNS tumors or meningiomas

Assess correlation of SST2A expression with uptake on DOTATATE PET, response to Lutathera therapy, and relevant clinical and molecular features within the confines of a Phase I/II study in patients with recurrent or progressive High-Grade CNS tumors or meningiomas treated with Lutathera

To estimate the maximum tolerated dose (MTD) of Lutathera in pediatric patients between 4 and \<12 years of age with recurrent and/or progressive high-grade CNS tumors or meningiomas that demonstrate uptake on DOTATATE PET.

To estimate the recommended Phase II dose (RP2D) of Lutathera in pediatric patients between 4 and \<12 years of age with recurrent and/or progressive high-grade CNS tumors or meningiomas that demonstrate uptake on DOTATATE PET.

To define and describe the toxicities of Lutathera in pediatric patients with recurrent and/or progressive high-grade CNS tumors or meningiomas that demonstrate uptake on DOTATATE PET. This will include calculating the number of participants with Lutathera-related adverse events as assessed by CTCAE v 5.0

To assess efficacy, evaluated by 6 month progression-free survival, of treatment with Lutathera in adolescent and young adult patients age ≥12 years with recurrent and/or progressive high-grade CNS tumors or meningiomas that demonstrate uptake on DOTATATE PET

To evaluate the objective response rate of Lutathera in adolescent and young adult patients age ≥12 years with recurrent and/or progressive high-grade CNS tumors or meningiomas that demonstrate uptake on DOTATATE PET.

To establish the safety and toxicity of Lutathera 200 mCi every 8-week dosing in adolescent and young adult patients age ≥12 years with recurrent and/or progressive high-grade CNS tumors or meningiomas that demonstrate uptake on DOTATATE PET. This will include calculating the number of participants with, as well as severity and frequency of, Lutathera-related adverse events as assessed by CTCAE v 5.0

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase I Study to Assess the Tolerability of 225Ac-DOTATATE in Patients With Refractory and Relapsing Multiple Myeloma Expressing Somatostatin Receptors	NCT06411301	Multiple Myelom... Multiple Myelom... Multiple Myelom...	225Ac-DOTATATE	18 Years -	Jules Bordet Institute
Systemic Targeted Adaptive RadioTherapy of NeuroEndocrine Tumors.	NCT05387603	Neuroendocrine ...	177Lu-DOTATOC Capecitabine	18 Years -	Lund University Hospital
Study to Evaluate the Effect of Age (Geriatric) and Kidney Function on the Safety, Efficacy and Pharmacokinetics of OctreoScan in Patients Who Have New or Recurrent Tumors	NCT00944372	Solid Tumors	Indium In-111 p...	18 Years -	Mallinckrodt
A Phase I Study to Assess the Tolerability of 225Ac-DOTATATE in Patients With Refractory and Relapsing Multiple Myeloma Expressing Somatostatin Receptors	NCT06411301	Multiple Myelom... Multiple Myelom... Multiple Myelom...	225Ac-DOTATATE	18 Years -	Jules Bordet Institute
Systemic Targeted Adaptive RadioTherapy of NeuroEndocrine Tumors.	NCT05387603	Neuroendocrine ...	177Lu-DOTATOC Capecitabine	18 Years -	Lund University Hospital
Lutathera for Treatment of Recurrent or Progressive High-Grade CNS Tumors	NCT05278208	High Grade Glio... Meningioma Embryonal Tumor Medulloblastoma Anaplastic Epen... Recurrent Diffu... Recurrent Malig... Recurrent Medul... Recurrent Prima... Refractory Diff... Refractory Mali... Refractory Medu... Refractory Prim...	LUTATHERA® (Lut...	4 Years -	Nationwide Children's Hospital

Spots Global Cancer Trial Database for somatostatin receptor