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

January 2, 2018 updated by: Grupo Espanol de Tumores Neuroendocrinos

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)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

43

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
    • Barcelona
      • Hospitalet de Llobregat, Barcelona, Spain, 08907
        • Instituto Catalan de Oncologia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Everolimus + Octreotide LAR treatment
Drug: Everolimus
Everolimus 10mg/day
Other Names:
  • Afinitor
Drug: octreotide LAR
30 mg each 28 days
Other Names:
  • Sandostatin LAR

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of patients with progression-free survival (PFS)
Time Frame: After 12 month of study treatment
Rate of patients
After 12 month of study treatment

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Grupo Espanol de Tumores Neuroendocrinos

Investigators

  • Study Chair: Ramón Salazar, MD, PhD, Grupo Espanol de Tumores Neuroendocrinos

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 8, 2011

Primary Completion (Actual)

September 1, 2014

Study Completion (Actual)

June 7, 2017

Study Registration Dates

First Submitted

March 26, 2012

First Submitted That Met QC Criteria

March 29, 2012

First Posted (Estimate)

March 30, 2012

Study Record Updates

Last Update Posted (Actual)

January 3, 2018

Last Update Submitted That Met QC Criteria

January 2, 2018

Last Verified

May 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GETNE 1003
  • CRAD001KES08T (Other Grant/Funding Number: Novartis Farmacéutica S.A.)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

As per Spanish local regulations

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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