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 4, 2013
Last verified: September 2013

March 26, 2012
September 4, 2013
June 2011
May 2014   (final data collection date for primary outcome measure)
Percentage of patients with progression-free survival (PFS) [ Time Frame: After 12 month of study treatment ] [ Designated as safety issue: No ]
Rate of patients
Progression Free Survival (PFS) [ Time Frame: After 12 month of study treatment ] [ Designated as safety issue: No ]
Rate of patients
Complete list of historical versions of study NCT01567488 on ClinicalTrials.gov Archive Site
  • 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 ]
IGF1R and S6K phosphorylation [ Time Frame: At baseline ] [ Designated as safety issue: No ]
Activation status of mTOR pathway.
Not Provided
Not Provided
 
Everolimus Combined With Octreotide LAR to Treat Advanced GI NET
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.

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.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Gastrointestinal Neoplasms
  • Drug: Everolimus
    Everolimus 10mg/day
    Other Name: Afinitor
  • Drug: octreotide LAR
    30 mg each 28 days
    Other Name: Sandostatin LAR
Experimental: Everolimus + Octreotide LAR treatment
Interventions:
  • Drug: Everolimus
  • Drug: octreotide LAR
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
40
May 2014
May 2014   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Spain
 
NCT01567488
GETNE 1003, CRAD001KES08T
Yes
Grupo Espanol de Tumores Neuroendocrinos
Grupo Espanol de Tumores Neuroendocrinos
Not Provided
Study Chair: Ramón Salazar, MD, PhD Grupo Espanol de Tumores Neuroendocrinos
Grupo Espanol de Tumores Neuroendocrinos
September 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP