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

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ClinicalTrials.gov Identifier: NCT01567488
Recruitment Status : Completed
First Posted : March 30, 2012
Last Update Posted : January 3, 2018
Sponsor:
Information provided by (Responsible Party):
Grupo Espanol de Tumores Neuroendocrinos

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.


Condition or disease Intervention/treatment Phase
Gastrointestinal Neoplasms Drug: Everolimus Drug: octreotide LAR Phase 2

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  (Clinical Trial)
Actual Enrollment : 43 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : June 8, 2011
Actual Primary Completion Date : September 1, 2014
Actual Study Completion Date : June 7, 2017


Arm Intervention/treatment
Experimental: Everolimus + Octreotide LAR treatment Drug: Everolimus
Everolimus 10mg/day
Other Name: Afinitor

Drug: octreotide LAR
30 mg each 28 days
Other Name: Sandostatin LAR




Primary Outcome Measures :
  1. Percentage of patients with progression-free survival (PFS) [ Time Frame: After 12 month of study treatment ]
    Rate of patients


Secondary Outcome Measures :
  1. 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.

  2. Rate of patients with objective responses [ Time Frame: Each three cycles ]
    Includes duration of response

  3. 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.

  4. 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.

  5. Percentage of patients with Adverse Events [ Time Frame: Each cycle ]
    Ocurred during the trial and up to 30 days after the last dose.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01567488


Locations
Spain
Instituto Catalán de Oncologia
Hospitalet de Llobregat, Barcelona, Spain, 08907
Sponsors and Collaborators
Grupo Espanol de Tumores Neuroendocrinos
Investigators
Study Chair: Ramón Salazar, MD, PhD Grupo Espanol de Tumores Neuroendocrinos

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Grupo Espanol de Tumores Neuroendocrinos
ClinicalTrials.gov Identifier: NCT01567488     History of Changes
Other Study ID Numbers: GETNE 1003
CRAD001KES08T ( Other Grant/Funding Number: Novartis Farmacéutica S.A. )
First Posted: March 30, 2012    Key Record Dates
Last Update Posted: January 3, 2018
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: As per Spanish local regulations

Keywords provided by Grupo Espanol de Tumores Neuroendocrinos:
Advanced
Non functioning
Well differentiated

Additional relevant MeSH terms:
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Everolimus
Sirolimus
Octreotide
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Gastrointestinal Agents
Antineoplastic Agents, Hormonal