Clinical Trials

Date: 2017-01-12

Type of information: Publication of results in a medical journal

phase: 3

Announcement: publication of results in The New English Journal of Medicine

Company: Advanced Accelerator Applications (France)

Product: Lutathera® ([177]Lutetium-DOTA[0]-Tyr[3]-Octreotate)

Action mechanism:

• peptide/radiopharmaceutical product. Lutathera®, is a radiolabeled somatostatin analog that selectively targets somatostatin receptors which are over-expressed in some tumor types. It acts like a Trojan horse, delivering [177]Lu directly into the tumour cell. [177]Lu is an instable particle that releases an electron which, as in radiotherapy, is capable of killing the tumors. It also releases a gamma ray, which exits the body and enables physicians to image and evaluate the progress of the treatment via a SPECT (Single Photon Emission Computed Tomography) camera. Lutathera® is an  example of a theragnostic drug, since its efficacy can be evaluated and monitored using imaging at every therapeutic injection, without additional costs.

Disease: inoperable, progressive, somatostatin receptor positive, midgut carcinoid tumors

Therapeutic area: Cancer - Oncology

Country: Austria, Belgium, France, Germany, Italy, Portugal, Spain, UK, USA

Trial details:

• The study, known as NETTER-1, is a Phase III, international, multi-center, randomised, comparator controlled, parallel-group study evaluating the efficacy and safety of Lutathera® compared to Novartis' Sandostatin® LAR in patients with inoperable, progressive, somatostatin receptor positive, midgut carcinoid tumors. The primary endpoint is the assessment of Progression-Free Survival (PFS). Secondary endpoints include safety, Objective Response Rate (ORR), Time to Tumour Progression (TTP), Overall Survival (OS) and Quality of Life (QoL). The trial is being managed in collaboration with Pierrel Research International. It will include 200 patients across 51 centers in nine different countries (Austria, Belgium, France, Germany, Italy, Portugal, Spain, UK and the US).

Latest news:

• • On January 12, 2017, Advanced Accelerator Applications announced that the New England Journal of Medicine published the results of the NETTER-1 Phase III study evaluating efficacy and safety of Lutathera® (lutetium-177 dotatate), an investigational drug, in patients with advanced, progressive somatostatin receptor-positive midgut neuroendocrine tumors.
• In this study, the primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), overall survival, safety, and tolerability. The NETTER-1 study met its primary endpoint by demonstrating that treatment with Lutathera® was associated with a statistically significant and clinically meaningful 79% reduction in risk of disease progression or death versus treatment with a high dose (60 mg) of Octreotide LAR (hazard ratio 0.21, 95% Confidence Interval: 0.13-0.33; p<0.0001). The estimated PFS rate at month 20 was 65.2% (95% Confidence Interval: 50.0-76.8) in the Lutathera® arm and 10.8% (95% Confidence Interval: 3.5-23.0) in the control arm. Median PFS was 8.4 months in the control arm, and had not yet been reached in the Lutathera® arm. Significant treatment benefits associated with Lutathera® were observed irrespective of stratification factors and prognostic factors. The response rate of 18% in the Lutathera® arm (compared to 3% with Octreotide) is also notable given that response rates above 5% have not been observed in large randomized clinical trials investigating other systemic therapies in this population. Although the trial has not reached the point at which median overall survival can be calculated, interim analysis suggests an overall survival improvement. Importantly, Lutathera® when administered concomitantly with a renal-protective agent, had low rates of grade three or four hematological toxicity, and no evidence of nephrotoxicity observed over the study timeframe (median follow-up time 14 months).
• • On October 8, 2014, THERAMetrics announced that its fully-owned company Pierrel Research Italy has been selected by Advanced Accelerator Applications, to extend the conduct of its international Phase III clinical trial NETTER-1 for Lutathera®, with the aim to compare Lutathera® with the current standard of care in patients with inoperable, progressive, somatostatin receptor positive midgut neuroendocrine tumours. The total budget for the completion of the study is estimated at 7.6 mio EUR. Pierrel Research will continue to provide full services for the clinical trial to Advanced Accelerator Applications including Trial Preparation, EU Regulatory Submissions, Site Management, Safety Management, eCRF and IWRS Set-up, Data Management, Statistics, Clinical Study Report, Project management, IMP services, and coordination of Central Lab and Imaging Services.
• • On October 16, 2013, Advanced Accelerator Applications (AAA) has announced that the 100-patient milestone has been reached for the NETTER-1 study, an international Phase III clinical trial evaluating the effect of Lutathera® in patients with inoperable progressive midgut carcinoid tumors. The rate of recruitment has accelerated in both Europe and the US, with 68 additional patients consenting to take part in the study (26 in Europe and 42 in the US) in the past six months. As of today, 43 sites have been initiated (31 in Europe, 12 in US), and 23 of them are actively recruiting.AAA expects results from the study to be published in 2015 and hopes to obtain marketing authorization in H1 2017. Phase II results of Lutathera® in patients with progressive midgut carcinoid showed Progression-Free Survival of over 45 months compared to the reported 14.6 months of Novartis’ Sandostatin® LAR. Lutathera® is currently used on a named patient basis or compassionate use for pre-marketing sales in several European countries (Austria, Estonia, Finland, Greece, Portugal, Spain, Switzerland and the UK) when no alternative therapeutic option is available and under specific authorization.
• • On September 19, 2012, Advanced Accelerator Applications has announced the initiation of an international Phase III clinical trial evaluating the effect of Lutathera®, an investigational peptide, in patients with inoperable progressive midgut carcinoid. The first European patient was enrolled on July 20th 2012 in Madrid, Spain. The FDA approved the trial on September 10th and the first patient is expected to be enrolled in the US during the fourth quarter of 2012.

Is general: Yes