Everolimus Combined With Octeotride LAR to Treat Advanced GI NET (EVERLAR)
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Purpose
The underlying hypothesis of the synergistic activity of octeotride and everolimus is based on the combination of a) a direct action of everolimus over mTOR, and b) the inhibitory effect of octeotride on the IGF-I 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 octeotride LAR® in non-functioning GI NET.
| Condition | Intervention | Phase |
|---|---|---|
|
Gastrointestinal Neoplasms |
Drug: Everolimus Drug: octeotride 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 Octeotride LAR® in Adult Patients With Advanced, Non-functioning, Well-differentiated Gastrointestinal Neuroendocrine Tumours (GI NET) |
- Percentage of patients with PFS [ Time Frame: After 12 month of study treatment ] [ Designated as safety issue: No ]Rate of patients
- Number of patients positive for IGF1R and 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 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: | March 2014 |
| Estimated Primary Completion Date: | December 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: Everolimus + Octeotride LAR treatment |
Drug: Everolimus
Everolimus 10mg/day
Other Name: Afinitor
Drug: octeotride 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 |
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| Contact: Ramon Salazar, MD, PhD | 0034 93 2607739 | ramonsalazar@iconcologia.net |
| Spain | |
| Instituto Catalán de Oncologia | Recruiting |
| Hospitalet de Llobregat, Barcelona, Spain, 08907 | |
| Contact: Ramón Salazar, MD, PhD 0034 93 2607739 ramonsalazar@iconcologia.net | |
| Principal Investigator: Alexander Teule, MD | |
| 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: | April 10, 2012 |
| Health Authority: | Spain: Spanish Agency of Medicines |
Keywords provided by Grupo Espanol de Tumores Neuroendocrinos:
|
Advanced Non functioning Well differentiated |
Additional relevant MeSH terms:
|
Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neuroendocrine Tumors Neoplasms by Site Digestive System Diseases Gastrointestinal Diseases Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms, Nerve Tissue Everolimus |
Sirolimus Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Antibiotics, Antineoplastic Antineoplastic Agents Therapeutic Uses Antifungal Agents Anti-Infective Agents Anti-Bacterial Agents |
ClinicalTrials.gov processed this record on May 23, 2013