TheranosticTrials.org

Clinical Trial · NCT03972488

Study to Evaluate the Efficacy and Safety of Lutathera in Patients With Grade 2 and Grade 3 Advanced GEP-NET

Overview

The aim of NETTER-2 was to determine if Lutathera in combination with long-acting octreotide prolongs progression free survival (PFS) in gastroenteropancreatic neuroendocrine tumor (GEP-NET) patients with high proliferation rate tumors (G2 and G3), when given as a first line treatment compared to treatment with high dose (60 mg) long-acting octreotide. Somatostatin analog (SSA) naive patients were eligible, as well as patients previously treated with SSAs in the absence of progression.

Sponsor

Advanced Accelerator Applications

Phase

Phase 3

Contacts

Novartis Pharmaceuticals (STUDY_DIRECTOR)

ClinicalTrials.gov

NCT03972488

Drug / Compound

DOTATATE

Isotope(s):
Target(s):
  • SSTR2
Ligand Class: Peptides
Chelator: DOTA

Eligibility

Inclusion

  • Ki67 index ≥10 and ≤ 55%
  • Expression of somatostatin receptors on all target lesions documented by CT/MRI scans, assessed by any of the following somatostatin receptor imaging (SRI) modalities within 3 months prior to randomization: \[68Ga\]-DOTA-TOC (e.g. Somakit-TOC®) PET/CT (or MRI when applicable based on target lesions) imaging, \[68Ga\]-DOTA-TATE PET/CT (or MRI when applicable based on target lesions) imaging (e.g. NETSPOT®), Somatostatin Receptor scintigraphy (SRS) with \[111In\]-pentetreotide (Octreoscan® SPECT/CT), SRS with \[99mTc\]-Tektrotyd, \[64Cu\]-DOTA-TATE PET/CT (or MRI when applicable based on target lesions) imaging.
  • Karnofsky Performance Score (KPS) ≥ 60
  • The tumor uptake observed in the target lesions must be \> normal liver uptake.
  • Presence of at least 1 measurable site of disease
  • 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.

Exclusion

  • Current spontaneous urinary incontinence
  • Documented RECIST progression to previous treatments for the current GEP-NET at any time prior to randomization
  • Total bilirubin \> 3 x ULN
  • 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 treatment period (including cross-over and re-treatment, if applicable) and for 7 months after study drug discontinuation
  • Uncontrolled diabetes mellitus as defined by hemoglobin A1c value \> 7.5%
  • 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.
  • Any previous radioembolization, chemoembolization and radiofrequency ablation for GEP-NET
  • 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.
  • Prior external beam radiation therapy to more than 25% of the bone marrow.
  • Creatinine clearance \< 40 mL/min calculated by the Cockroft Gault method
  • Patients who have participated in any therapeutic clinical study/received any investigational agent within the last 30 days
  • 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 or MRI with contrast to document stable disease prior to randomization in the study.
  • Pregnancy or lactation
  • QTcF \> 470 msec for females and QTcF \> 450 msec for males or congenital long QT syndrome
  • Hypersensitivity to any somatostatin analogues, the IMPs active substance or to any of the excipients.
  • Hyperkaleamia \> 6.0 mmol/L (CTCAE Grade 3) which is not corrected prior to study enrolment
  • Peptide receptor radionuclide therapy (PRRT) at any time 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 via echocardiography. 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 randomization.
  • Hb concentration \< 5.0 mmol/L (\<8.0 g/dL); WBC \< 2x10E9/L (2000/mm3); platelets \< 75x10E9/L (75x10E3/mm3)
  • Patients with any other significant medical, psychiatric, or surgical condition, currently uncontrolled by treatment, which may interfere with the completion of the study.
  • Any previous therapy with Interferons, Everolimus (mTOR-inhibitors), chemotherapy or other systemic therapies for GEP-NET administered for more than 1 month or within 12 weeks prior to randomization in the study.
  • Serum albumin \< 3.0 g/dL unless prothrombin time is within the normal range
  • Any surgery within 12 weeks prior to randomization in the study
  • 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