Study to Evaluate the Efficacy and Safety of [177Lu]Lu-DOTA-TATE in Patients With Grade 1 and Grade 2 Advanced GEP-NET

Launched by NOVARTIS PHARMACEUTICALS · Jan 15, 2025

Keywords

ClinConnect Summary

This clinical trial is studying a treatment called [177Lu]Lu-DOTA-TATE combined with a medication called octreotide for patients with advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that are positive for somatostatin receptors. The goal is to see if this combination is more effective than using octreotide alone in newly diagnosed patients with Grade 1 and Grade 2 tumors that cannot be surgically removed and have a high disease burden. This means the tumors are significant in size or number and may be causing symptoms.

To join the trial, participants need to be at least 12 years old and have a confirmed diagnosis of GEP-NET within the last six months. They should also show signs of high disease burden, such as having large tumors or experiencing symptoms like pain or weight loss. Participants will undergo tests to ensure their tumors respond positively to the treatment. Those who qualify can expect to receive either the new treatment or the standard care while being monitored for safety and effectiveness. It's important to know that this trial is not yet recruiting participants, so interested individuals will have to wait for it to start.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Presence of metastasized or locally advanced, unresectable (curative intent), histologically proven, well differentiated Grade 1 or Grade 2 (Ki-67 \<10%) gastroenteropancreatic neuroendocrine tumor (GEP-NET) diagnosed within 6 months prior to screening.
• * Participants with high disease burden in the Investigator's opinion. Following criteria should be used as the guiding principle for determining high disease burden:
• • Primary tumor or a metastatic lesion \> 4 cm
• • More than one tumor or metastatic lesions measuring \> 2 cm
• • Elevated alkaline phosphatase \> 2.5 X upper limit of normal (ULN)
• • Presence of bone metastasis
• • Presence of peritoneal metastasis
• • Symptoms due to tumor volume such as pain, fatigue, weight loss, anorexia etc.
• • Symptoms due to hormone excess requiring active management
• • Additionally, participants who, in the Investigator's opinion, have high disease burden due to their disease characteristics not specified above could also be considered eligible.
• • Participants ≥ 12 years of age.
• * RLI somatostatin receptor (SSTR) uptake on all target lesions (defined by RECIST v1.1 criteria) at least as high as normal liver uptake assessed within 3 months prior to randomization. Any of the RLI modalities as available (some examples are listed below) can be used as per local practice:
• • \[68Ga\]Ga-DOTA-TOC PET/CT or PET/MRI
• • \[68Ga\]Ga-DOTA-TATE PET/CT or PET/MRI
• • \[64Cu\]Cu-DOTA-TATE PET/CT or PET/MRI
• • Somatostatin receptor scintigraphy (SRS) (planar and/or SPECT/CT) with \[111In\]In-pentetreotide
• • SRS (planar and/or SPECT/CT) with \[99mTc\]Tc-octreotide.
• * Adequate bone marrow and organ function as defined by the following laboratory values prior to receiving the first study treatment:
• • White blood cell (WBC) count ≥ 2 x 109/L
• • Platelet count ≥ 75 x 109/L
• • Hemoglobin (Hb) ≥ 8 g/dL
• • Creatinine clearance \> 40 mL/min calculated by the Cockcroft Gault method
• • Total bilirubin ≤ 3 x ULN
• • Potassium within normal limits. Potassium level of up to 6.0 millimoles per liter (mmol/L) is acceptable at study entry if associated with creatinine clearance within normal limits calculated using Cockcroft-Gault formula. Mild decrease (grade 1) below lower limit of normal (LLN) is acceptable at study entry if considered not clinically significant by Investigator.
• • ECOG performance status 0-1.
• • Presence of at least 1 measurable site of disease.
• Exclusion Criteria:
• • Prior administration of a therapeutic radiopharmaceutical for GEP-NET at any time prior to randomization in the study.
• • Any previous therapy with interferons, mTOR-inhibitors, chemotherapy or other systemic therapies except somatostatin analogues (SSAs) of GEP-NET. If as per Investigator's opinion a participant is candidate for such therapies, such participant must not be enrolled.
• • Participant who received more than 4 cycles of prior SSAs (e.g., octreotide long-acting release) are not eligible. In addition, any participant receiving treatment with short-acting octreotide, which cannot be interrupted for 24 h before the administration of \[177Lu\]Lu-DOTA-TATE, or any participant receiving treatment with SSAs, which cannot be interrupted for at least 4 weeks before the administration of \[177Lu\]Lu-DOTA-TATE.
• • Documented RECIST v1.1 progression during previous SSA treatments for the current GEP-NET at any time prior to randomization.
• • Any previous radioembolization, chemoembolization and radiofrequency ablation for GEP-NET.
• • Any major surgery within 12 weeks prior to randomization in the study.
• • Known brain metastases.
• • Participant with known intolerance to CT scans with intravenous (i.v.) contrast due to allergic reaction or renal insufficiency. If such a participant can be imaged with MRI, then the participant would not be excluded.
• • Hypersensitivity to any somatostatin analogues, to the Investigational Medicinal Products (IMPs) active substance or to any of the excipients.
• • Active severe urinary incontinence, severe voiding dysfunction, or urinary obstruction requiring an indwelling/condom catheter that, in the judgment of the Investigator, could prevent adhering to radiation safety instructions.
• • Other protocol-defined Inclusion/Exclusion criteria may apply.