NCT01567488

Phase II Study of Everolimus Combined With Octreotide LAR to Treat Advanced GI NET

A Phase II Study on Everolimus, an mTOR Inhibitor (Oral Formulation), With Octreotide LAR® in Adult Patients With Advanced, Non-functioning, Well-differentiated Gastrointestinal Neuroendocrine Tumours (GI NET)

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 43 (actual)
• Sponsor: Grupo Espanol de Tumores Neuroendocrinos · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The underlying hypothesis of the synergistic activity of octreotide and everolimus is based on the combination of a) a direct action of everolimus over mTOR (mammalian target of rapamycin), and b) the inhibitory effect of octreotide on the IGF-I (insulin like growth factor 1) system preventing the activation of the mTOR system by this factor. Both types of inhibition would completely cancel this signal transduction pathway, which is so important in neuroendocrine tumours. Furthermore, the biological study proposed in this protocol will allow for better establishing the relationship between the activation of the IGFR-PI3K-mTOR signal transduction pathway (i.e., the mTOR pathway stimulated by IGFR) and treatment response; this information is relevant since the IGFR-PI3K-mTOR activation status could be a response prediction factor. This study will provide significant additional information about the efficacy of the combination treatment of everolimus with octreotide LAR® in non-functioning GI NET.

Detailed description

Everolimus has been developed following two administration regimens: weekly and daily. Phase I pharmacodynamic studies recommend doses of 50 mg weekly and 10 mg/daily, based on its toxicity and inhibitory effect of the mTOR pathway in tumours; although the inhibition of this pathway has been demonstrated, the knowledge of response prediction factors has not been developed, in part due to the very low responses found in the population in phase I studies. These factors can be better outlined in a phase II study, where patients who have received fewer previous treatments can respond better, and where the profile of responders and non-responders can be identified more easily.

Conditions

• Gastrointestinal Neoplasms

Interventions

Type	Name	Description
DRUG	Everolimus	Everolimus 10mg/day
DRUG	octreotide LAR	30 mg each 28 days

Timeline

• Start date: 2011-06-08
• Primary completion: 2014-09-01
• Completion: 2017-06-07
• First posted: 2012-03-30
• Last updated: 2018-01-03

Locations

1 site across 1 country: Spain