177Lu-DOTA-EB-TATE in Adult Patients With Advanced, Well- Differentiated Neuroendocrine Tumors

Phase I, Open-Label Study of the Safety and Dosimetry of a 3-Dose Regimen of Escalating Doses of 177Lu-DOTA-EB-TATE in Adult Patients With Advanced, Well- Differentiated Neuroendocrine Tumors

This is a Phase I clinical trial to assess the safety and dosimetry profiles of 177Lu-DOTA-EB-TATE in patients with advanced, metastatic or inoperable, somatostatin receptor-positive, well-differentiated GEP-NETs.

Study Overview

• Status: Recruiting
• Conditions: Neuroendocrine Tumors
• Intervention / Treatment: Drug: 177Lu-DOTA-EB-TATE; Other: Amino Acid Solution

• Study Type: Interventional
• Enrollment (Estimated): 9
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Chris Pak; Phone Number: 610-738-7938; Email: cpak@mtarget.com

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
      • Contact: Lisa Bodei, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Ability to understand and willing to sign a written informed consent document

Aged 18 years or older

Histologically proven or cytologically confirmed, inoperable, GEP-NETs

Neuroendocrine tumors (NETs) of grade 1, 2 and 3 according to World Health Organization (WHO) 2017 classification

Measurable disease as defined by Response Criteria in Solid Tumors (RECIST) version 1.1

Overexpression of somatostatin receptors of the target lesions in 68Ga-DOTA-TATE positron emission tomography (PET)/computed tomography (CT) with SUV of lesions greater than normal liver in at least 1 lesion

A Cockcroft Gault calculated creatinine clearance > 60 mL/min

Karnofsky performance status scale ≥ 70%

Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation, including follow-up (7 months after the last dose of study drug for women and 4 months for men).

Previous local therapy (e.g., chemoembolization or bland embolization) is allowed if completed >4 weeks prior to study entry.

Previous surgery no less than 6 weeks prior to study entry.

Either no prior treatment with 177Lu-DOTA-TATE or at least 12 months progression-free survival (PFS) after prior treatment with 177Lu-DOTA-TATE

Exclusion Criteria:

Women who are pregnant or breastfeeding

History of allergic reactions attributed to compounds of similar chemical or biologic composition to 177Lu-DOTA-EB-TATE as assessed from medical records

Previous treatment with more than 4 cycles of 177Lu-DOTA-TATE

Participant has had prior chemotherapy, targeted cancer therapy, immunotherapy, or treatment with an investigational anticancer agent within 4 weeks or 4 half-lives whichever is longer, before the first administration of study drug.

Participant has not fully recovered from major surgery or significant traumatic injury prior the first dose of study drug or expects to have major surgery during the study period or within 3 months after the last dose of study drug.

Life expectancy < 6 months as assessed by the treating physician

> 80% liver involvement by tumor

> 25% bone marrow involvement by tumor

Poorly differentiated neuroendocrine neoplasms, such as poorly differentiated neuroendocrine carcinoma, small- and large-cell neuroendocrine carcinoma; mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN); Grade 3 neuroendocrine carcinomas (NEC)

Presence of somatostatin receptor negative lesions if they cannot be addressed with loco-regional therapies prior to the treatment start

Deteriorated renal function, as indicated by a serum creatinine clearance > 1.7 mg/dL

Deteriorated bone marrow function

Deteriorated liver function

Toxicities from prior therapies that have not resolved to grade 1 or grade 0

Active and clinically significant bacterial, fungal, or viral infection, including hepatitis B (HBV), hepatitis C (HBC), know human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS)-related illness

Known brain metastases and/or carcinomatous meningitis, unless these metastases have been treated and stabilized

Uncontrolled diabetes mellitus as defined by a HbA1c >9%

Impossibility to interrupt short-acting octreotide for 24 h before and 24 h after the administration of 177Lu-DOTA-EB-TATE; impossibility to have an interval of ≥4 weeks between octreotide and 177Lu-DOTA-EB-TATE

The use of somatostatin and its analogues within 4 months of a planned 177Lu-DOTA-EB-TATE treatment

Uncontrolled, intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

Prior external beam radiation therapy involving >25% of the bone marrow

Unmanageable urinary incontinence rendering the administration of 177Lu-DOTA-EB-TATE unsafe

Other known co-existing malignancies except non-melanoma skin cancer and carcinoma in situ of the uterine cervix, unless definitively treated and with no evidence of recurrence

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Peptide Receptor Radionucleotide Therapy (PRRT); The treatment regimen will consist of a single-dose intravenous administration of 177Lu-DOTA-EB-TATE per 6-week cycle, for a total of 2 cycles. The dose per cycle will be fixed for each patient and will be escalated in 3 different dose levels, from 50 mCi to 150 mCi (1.85 -5.55 GBq). Each dose of 177Lu-DOTA-EB-TATE will be administered in association with intravenous renal protective amino acid solutions.

Drug: 177Lu-DOTA-EB-TATE; Peptide Receptor Radionucleotide Therapy ( PRRT) using 177Lu-DOTA-EB-TATE with a defined number of cycles will be administered.; Other: Amino Acid Solution; The Amino acid solution to be used in this study will contain a mixture of lysine and arginine diluted in an electrolyte solution.; Other Names: Arginine-Lysine Solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To evaluate the safety of 177Lu-DOTA-EB-TATE assessed from the number of patients with treatment-related adverse events.	16-17 months
To identify the dose-limiting toxicities (DLTs) of escalating doses of 177Lu-DOTA-EB-TATE up to 150 mCi.	16-17 months
To determine if the maximum tolerated dose is among the explored doses of 50, 100 and 150 mCi.	16-17 months

Secondary Outcome Measures

Outcome Measure	Time Frame
To evaluate the differential safety of 177Lu-DOTA-EB-TATE, expressed as the number of patients with treatment-related adverse events following 177Lu-DOTA-EB-TATE.	16-17 months
To evaluate dosimetry levels in patients following 2 cycles of 177Lu-DOTA-EB-TATE.	16-17 months

Collaborators and Investigators

• Sponsor: Molecular Targeting Technologies, Inc.
• Collaborators: ClinSmart
• Investigators: Principal Investigator: Lisa Bodei, MD, PhD, Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2022
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): March 30, 2025

Study Registration Dates

• First Submitted: July 22, 2022
• First Submitted That Met QC Criteria: July 22, 2022
• First Posted (Actual): July 26, 2022

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Pharmaceutical Solutions; (177)Lu-DOTA-EB-TATE
• Other Study ID Numbers: MTTI-EBT-001; 21-362 (Other Identifier: Memorial Sloan-Kettering Cancer Center IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No