NCT01567488

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
43

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Jun 2011

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 8, 2011

Completed
10 months until next milestone

First Submitted

Initial submission to the registry

March 26, 2012

Completed
4 days until next milestone

First Posted

Study publicly available on registry

March 30, 2012

Completed
2.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2014

Completed
2.8 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 7, 2017

Completed
Last Updated

January 3, 2018

Status Verified

May 1, 2017

Enrollment Period

3.2 years

First QC Date

March 26, 2012

Last Update Submit

January 2, 2018

Conditions

Gastrointestinal Neoplasms

Keywords

AdvancedNon functioningWell differentiated

Outcome Measures

Primary Outcomes (1)

  • Percentage of patients with progression-free survival (PFS)

    Rate of patients

    After 12 month of study treatment

Secondary Outcomes (5)

  • Number of patients positive for insulin like growth factor 1 receptor (IGF1R) and ribosomal kinase S6 (S6K) phosphorylation.

    At baseline

  • Rate of patients with objective responses

    Each three cycles

  • Median and average of time for Overall survival

    At the end of the study

  • Rate of patients with an early decrease of chromogranin A (CgA) levels

    Each cycle

  • Percentage of patients with Adverse Events

    Each cycle

Study Arms (1)

Everolimus + Octreotide LAR treatment

EXPERIMENTAL
Drug: EverolimusDrug: octreotide LAR

Interventions

EverolimusDRUG

Everolimus 10mg/day

Also known as: Afinitor
Everolimus + Octreotide LAR treatment
octreotide LARDRUG

30 mg each 28 days

Also known as: Sandostatin LAR
Everolimus + Octreotide LAR treatment

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • Adequate bone marrow. liver and renal function

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Instituto Catalán de Oncologia

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Related Publications (1)

  • Capdevila J, Teule A, Barriuso J, Castellano D, Lopez C, Manzano JL, Alonso V, Garcia-Carbonero R, Dotor E, Matos I, Custodio A, Casanovas O, Salazar R; EVERLAR study investigators. Phase II Study of Everolimus and Octreotide LAR in Patients with Nonfunctioning Gastrointestinal Neuroendocrine Tumors: The GETNE1003_EVERLAR Study. Oncologist. 2019 Jan;24(1):38-46. doi: 10.1634/theoncologist.2017-0622. Epub 2018 May 23.

    PMID: 29794066DERIVED

MeSH Terms

Conditions

Gastrointestinal Neoplasms

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Digestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesGastrointestinal Diseases

Intervention Hierarchy (Ancestors)

SirolimusMacrolidesLactonesOrganic Chemicals

Study Officials

  • Ramón Salazar, MD, PhD

    Grupo Espanol de Tumores Neuroendocrinos

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 26, 2012

First Posted

March 30, 2012

Study Start

June 8, 2011

Primary Completion

September 1, 2014

Study Completion

June 7, 2017

Last Updated

January 3, 2018

Record last verified: 2017-05

Locations

ES(1)