- Presence of metastasized or locally advanced, inoperable (curative intent)
histologically proven, well differentiated Grade 2 or Grade 3 gastroenteropancreatic
neuroendocrine (GEP-NET) tumor diagnosed within 6 months prior to screening.
- Ki67 index ≥10 and ≤ 55%
- Patients ≥ 15 years of age and a body weight of > 40 kg at screening
- Expression of somatostatin receptors on all target lesions documented by CT/MRI scans,
assessed by the following somatostatin receptor imaging (SRI) modalities within 3
months prior to randomization: [68Ga]-DOTA-TOC (e.g. Somakit-TOC) PET/CT imaging or
[68Ga]-DOTA-TATE PET/CT imaging (e.g. NETSPOT) or Somatostatin Receptor scintigraphy
(SRS) with 111In-pentetreotide (Octreoscan SPECT/CT).
- The tumor uptake observed in the target lesions must be > normal liver uptake observed
on planar imaging.
- Karnofsky Performance Score (KPS) ≥ 60
- Presence of at least 1 measurable site of disease
- Patients who have provided a signed informed consent form to participate in the study,
obtained prior to the start of any protocol related activities
- Creatinine clearance < 40 mL/min calculated by the Cockroft Gault method
- Hb concentration < 5.0 mmol/L (<8.0 g/dL); WBC < 2x10E9/L (2000/mm3); platelets <
- Total bilirubin > 3 x ULN
- Serum albumin < 3.0 g/dL unless prothrombin time is within the normal range
- Pregnancy or lactation
- Women of child-bearing potential, defined as all women physiologically capable of
becoming pregnant, are not allowed to participate in this study UNLESS they are using
highly effective methods of contraception throughout the study and for 6 months after
study drug discontinuation
- Peptide receptor radionuclide therapy (PRRT) at any time prior to randomization in the
- Documented RECIST progression to previous treatments for the current GEP-NET at any
time prior to randomization
- Patients for whom in the opinion of the investigator other therapeutic options (eg
chemo-, targeted therapy) are considered more appropriate than therapy offered in the
study, based on patient and disease characteristics
- Any previous therapy with Interferons, Everolimus (mTOR-inhibitors), chemotherapy or
other systemic therapies administered for more than 1 month and within 12 weeks prior
to randomization in the study.
- Any previous radioembolization, chemoembolization and radiofrequency ablation
- Any surgery within 12 weeks prior to randomization in the study
- Known brain metastases, unless these metastases have been treated and stabilized for
at least 24 weeks, prior to screening in the study. Patients with a history of brain
metastases must have a head CT with contrast to document stable disease prior to
randomization in the study.
- Uncontrolled congestive heart failure (NYHA II, III, IV). Patients with history of
congestive heart failure who do not violate this exclusion criterion will undergo an
evaluation of their cardiac ejection fraction prior to randomization, preferably via
gated equilibrium radionuclide ventriculography. The results from an earlier
assessment (not exceeding 30 days prior to randomization) may substitute the
evaluation at the discretion of the Investigator, if no clinical worsening is noted.
The patient's measured cardiac ejection fraction in these patients must be ≥40% before
- QTcF > 470 msec for females and QTcF > 450 msec for males or congenital long QT
- Uncontrolled diabetes mellitus as defined by a fasting blood glucose > 2 ULN
- Hyperkaleamia > 6.0 mmol/L (CTCAE Grade 3) which is not corrected prior to study
- Any patient receiving treatment with short-acting octreotide, which cannot be
interrupted for 24 h before and 24 h after the administration of Lutathera, or any
patient receiving treatment with SSAs (e.g. octreotide long-acting), which cannot be
interrupted for at least 6 weeks before the administration of Lutathera, unless the
tumor uptake on target lesions observed by study-permitted somatostatin receptor
imaging (SRI) modalities during continued long-acting SSA treatment is greater than
the liver uptake observed by planar imaging.
- Patients with any other significant medical, psychiatric, or surgical condition,
currently uncontrolled by treatment, which may interfere with the completion of the
- Prior external beam radiation therapy to more than 25% of the bone marrow.
- Current spontaneous urinary incontinence
- Other known co-existing malignancies except non-melanoma skin cancer and carcinoma in
situ of the uterine cervix, unless definitively treated and proven no evidence of
recurrence for 5 years
- Patient with known incompatibility to CT Scans with IV contrast due to allergic
reaction or renal insufficiency. If such a patient can be imaged with MRI, then the
patient would not be excluded.
- Patients with known intolerance or hypersensitivity to any somatostatin analogs
- Patients who have participated in any therapeutic clinical study/received any
investigational agent within the last 30 days