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

Gastrointestinal Neoplasms Clinical Trial

— EVERLAR  

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01567488
• Other study ID #: GETNE 1003
• Secondary ID: CRAD001KES08T
• Status: Completed
• Phase: Phase 2
• First received: March 26, 2012
• Last updated: January 2, 2018
• Start date: June 8, 2011
• Est. completion date: June 7, 2017

Study information

• Verified date: May 2017
• Source: Grupo Espanol de Tumores Neuroendocrinos
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: June 7, 2017
• Est. primary completion date: September 1, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of non-operable or metastatic non-functioning, well differentiated advanced GI NET, confirmed by cytology or histology. In case of liver metastasis, neuroendocrine tumours of unknown origin are accepted.

• Confirmation of diagnosis of neuroendocrine carcinoma of low to intermediate histology grade

• Radiologically documented disease progression within 12 months prior to inclusion in the study. If the patient received anticancer treatment within the past 12 months, disease progression must be documented by radiology during or after taking this medication

• Adequate bone marrow. liver and renal function

Exclusion Criteria:

• Previous treatment with mTOR inhibitors (sirolimus, temsirolimus, everolimus, deforolimus).

• Patients with any serious disease and/or an uncontrolled clinical condition

• Patients on chronic treatment with corticosteroids or any other immunosuppressive agent

Related Conditions & MeSH terms

• Digestive System Neoplasms
• Gastrointestinal Neoplasms

Intervention

Drug:
• Everolimus
Everolimus 10mg/day
• octreotide LAR
30 mg each 28 days

Locations

Country	Name	City	State
Spain	Instituto Catalán de Oncologia	Hospitalet de Llobregat	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Grupo Espanol de Tumores Neuroendocrinos

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of patients with progression-free survival (PFS)	Rate of patients	After 12 month of study treatment
Secondary	Number of patients positive for insulin like growth factor 1 receptor (IGF1R) and ribosomal kinase S6 (S6K) phosphorylation.	Activation status of mTOR pathway.	At baseline
Secondary	Rate of patients with objective responses	Includes duration of response	Each three cycles
Secondary	Median and average of time for Overall survival	Time from inclusion date up to date of death for any reason.	At the end of the study
Secondary	Rate of patients with an early decrease of chromogranin A (CgA) levels	CgA levels will be measured when increased at baseline and up to its normalization.	Each cycle
Secondary	Percentage of patients with Adverse Events	Ocurred during the trial and up to 30 days after the last dose.	Each cycle