Overview

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.

Eligibility

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