FIRST PIVOTAL PHASE III STUDY EVALUATING 177Lu-DOTATATE IN MIDGUT NEUROENDOCRINE TUMOURS
Lutathera (or 177Lu-DOTATATE) is a novel compound currently under development for the treatment of midgut neuroendocrine tumours. Lutathera belongs to an emerging form of treatments called peptide receptor radionuclide therapy (PRRT) which involves targeting carcinoid tumors with radiolabeled somatostatin analogue peptides.
The unmet medical need for an effective treatment of inoperable, advanced neuroendocrine tumors (NETs) is well known. There are no therapeutic options for patients with NETs other than pancreatic (about 90% of NETs) who are progressive under somatostatin analogues.
PRRT meets this specific medical need and leading key scientific societies such as NANETS1, ESMO2 and ENETS3 have included this therapy in their treatment guidelines for non-resectable midgut or gastro-entero-pancreatic NETs.
Furthermore, preliminary scientific evidence of efficacy and safety of tumor-targeted PRRT has urged several European countries (currently Austria, Estonia, Finland, France, Greece, Portugal, Spain, Switzerland, UK) to implement compassionate use/named patient basis programs. Hence, since 2000, thousands of patients have been treated with 177Lu-DOTA0-Tyr3-Octreotate (177Lu-DOTATATE) showing promising results in terms of tumor response, safety and quality of life improvement.
Currently at the end of phase III development with the Netter-1 pivotal study, Lutathera is the most advanced candidate in development for PRRT.
Design: Netter-1 is the first Phase III multicentric, stratified, open, randomized, controlled, parallel-group study, comparing 177Lu-DOTATATE with Octreotide LAR (Sandostatin® LAR Depot) in patients with inoperable, progressive, somatostatin receptor positive midgut carcinoid tumours.
Primary endpoint: Progression Free Survival (PFS) as per RECIST 1.1 criteria. Objective tumor assessment is performed every 12 weeks until progression is documented using an independent image reading center.
Main secondary endpoints: Objective Response Rate (ORR), Overall Survival (OS), Time To Progression (TTP), safety, tolerability and health-related quality of life. Dosimetry, pharmacokinetics and ECG evaluations are also performed in a subset of patients.
Protocol: Treatment with a cumulative dose of 29.6 GBq of 177Lu-DOTATATE (4 administrations of 7.4 GBq every 8 weeks) plus supportive care with 30 mg Sandostatin® LAR on one arm. Compared to 60 mg Sandostatin® LAR alone every 4-weeks on the other arm. Patients must have progressive disease while on a fixed dose of Sandostatin® LAR at baseline. Presence of somastotatin receptors on all target lesions shall be confirmed by OctreoScan® imaging.
The OS period includes 18-month accrual plus a 5-year follow-up starting from the last patient’s randomization date. Tumor response is centrally assessed in both arms, every 12 +/-1 week(s) from the randomization date, according to the RECIST criteria. Efficacy is blindly and independently assessed through image review by qualified readers.
Patients shall remain under treatment until disease progression or unacceptable toxicity or inability/unwillingness to comply with study requirements or consent withdrawal.
Participating sites: 36 in Europe and 15 in the USA.
The first patient was enrolled in July 2012. The study will randomize 230 patients, 1:1 to each arm.
The Analysis of primary endpoint (PFS) shall start after 74 evaluable and centrally confirmed events.
An independent Data Safety Monitoring Board (DSMB) is supervising the conduct of the study and regularly assesses the study safety outcome.
The recruitment is now complete.
More information on the Netter-1 trial can be found at: https://clinicaltrials.gov/ct2/show/NCT01578239
177Lu-DOTATATE Mode of Action video
- Boudreaux et al. 2010, The NANETS Consensus Guidelines for the Diagnosis and Management of Neuroendocrine Tumors.
- Eriksson et al. 2008, Consensus Guidelines for the Management of Patients with Digestive Neuroendocrine Tumors – Well-differentiated Jujenal-Ileal Tumor/Carcinoma (ENETS Guidelines)
- Oberg et al. 2012, Neuroendocrine Gastro-entero-pancreatic tumors : ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.