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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Grupo Espanol de Tumores Neuroendocrinos
ClinicalTrials.gov Identifier:
NCT01567488
First received: March 26, 2012
Last updated: September 15, 2014
Last verified: September 2014
  Purpose

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 Intervention Phase
Gastrointestinal Neoplasms
Drug: Everolimus
Drug: octreotide LAR
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by Grupo Espanol de Tumores Neuroendocrinos:

Primary Outcome Measures:
  • Percentage of patients with progression-free survival (PFS) [ Time Frame: After 12 month of study treatment ] [ Designated as safety issue: No ]
    Rate of patients


Secondary Outcome Measures:
  • Number of patients positive for insulin like growth factor 1 receptor (IGF1R) and ribosomal kinase S6 (S6K) phosphorylation. [ Time Frame: At baseline ] [ Designated as safety issue: No ]
    Activation status of mTOR pathway.

  • Rate of patients with objective responses [ Time Frame: Each three cycles ] [ Designated as safety issue: No ]
    Includes duration of response

  • Median and average of time for Overall survival [ Time Frame: At the end of the study ] [ Designated as safety issue: No ]
  • Rate of patients with an early decrease of chromogranin A (CgA) levels [ Time Frame: Each cycle ] [ Designated as safety issue: No ]
    CgA levels will be measured when increased at baseline and up to its normalization.

  • Percentage of patients with Adverse Events [ Time Frame: Each cycle ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 40
Study Start Date: June 2011
Estimated Study Completion Date: May 2015
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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
  More Information

No publications provided

Responsible Party: Grupo Espanol de Tumores Neuroendocrinos
ClinicalTrials.gov Identifier: NCT01567488     History of Changes
Other Study ID Numbers: GETNE 1003, CRAD001KES08T
Study First Received: March 26, 2012
Last Updated: September 15, 2014
Health Authority: Spain: Spanish Agency of Medicines

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

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

ClinicalTrials.gov processed this record on October 23, 2014