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

Sponsor
Molecular Targeting Technologies, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT05475210
Collaborator
ClinSmart (Industry)
9
1
1
21.4
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Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
9 participants
Allocation:
N/A
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase I, Open-Label Study of the Safety and Dosimetry of a 3-Dose Regimen of Escalating Doses of 177Lu-DOTA-EB-TATE in Untreated (Naïve) Adult Patients With Advanced, Well- Differentiated Neuroendocrine Tumors
Actual Study Start Date :
Jun 18, 2022
Anticipated Primary Completion Date :
Dec 31, 2023
Anticipated Study Completion Date :
Mar 30, 2024

Arms and Interventions

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
  • Outcome Measures

    Primary Outcome Measures

    1. To evaluate the safety of 177Lu-DOTA-EB-TATE assessed from the number of patients with treatment-related adverse events. [16-17 months]

    2. To identify the dose-limiting toxicities (DLTs) of escalating doses of 177Lu-DOTA-EB-TATE up to 150 mCi. [16-17 months]

    3. To determine if the maximum tolerated dose is among the explored doses of 50, 100 and 150 mCi. [16-17 months]

    Secondary Outcome Measures

    1. 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]

    2. To evaluate dosimetry levels in patients following 2 cycles of 177Lu-DOTA-EB-TATE. [16-17 months]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    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 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Memorial Sloan Kettering Cancer Center New York New York United States 10065

    Sponsors and Collaborators

    • Molecular Targeting Technologies, Inc.
    • ClinSmart

    Investigators

    • Principal Investigator: Lisa Bodei, MD, PhD, Memorial Sloan Kettering Cancer Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Molecular Targeting Technologies, Inc.
    ClinicalTrials.gov Identifier:
    NCT05475210
    Other Study ID Numbers:
    • MTTI-EBT-001
    • 21-362
    First Posted:
    Jul 26, 2022
    Last Update Posted:
    Jul 26, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jul 26, 2022