Gastrointestinal NeoplasmsPhase 2EVERLARNCT01567488
Phase II Study of Everolimus Combined With Octreotide LAR to Treat Advanced GI NET
A Phase 2 study testing Everolimus and octreotide LAR in people with Gastrointestinal Neoplasms, run by Grupo Espanol de Tumores Neuroendocrinos at 1 site in Spain.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastrointestinal Neoplasms
- What is being tested?
- Everolimus and octreotide LAR
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 1 siteSpain
- Study dates
- 8 Jun 2011to 7 Jun 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Spain1 site
Instituto Catalán de Oncologia
L'Hospitalet de Llobregat, Barcelona, 08907
About this study
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)
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.
Read the 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.
- Conditions
- Gastrointestinal Neoplasms
- Being tested
- Everolimus, octreotide LAR
- Keywords
- Advanced, Non functioning, Well differentiated
- Medical subject headings
- Gastrointestinal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EverolimusDrug
Also called Afinitor
Everolimus 10mg/day
octreotide LARDrug
Also called Sandostatin LAR
30 mg each 28 days
| Study group | Role | What they receive |
|---|---|---|
| Everolimus + Octreotide LAR treatment | Experimental | Not described Receives: Drug: Everolimus; Drug: octreotide LAR |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of patients with progression-free survival (PFS)
Rate of patients
Measured: 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.
Activation status of mTOR pathway.
Measured: At baseline
Rate of patients with objective responses
Includes duration of response
Measured: Each three cycles
Median and average of time for Overall survival
Time from inclusion date up to date of death for any reason.
Measured: At the end of the study
Rate of patients with an early decrease of chromogranin A (CgA) levels
CgA levels will be measured when increased at baseline and up to its normalization.
Measured: Each cycle
Percentage of patients with Adverse Events
Ocurred during the trial and up to 30 days after the last dose.
Measured: Each cycle
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2012 (estimated)
- Study start8 Jun 2011
- Primary completion1 Sep 2014
- Study completion7 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Gastrointestinal NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Grupo Espanol de Tumores Neuroendocrinos
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ramón Salazar, MD, PhD, Study chair, Grupo Espanol de Tumores Neuroendocrinos
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01567488
- Sponsor's protocol ID
- GETNE 1003
- Other IDs
- CRAD001KES08T
- Acronym
- EVERLAR
- Status last verified
- May 2017
- First submitted
- 26 Mar 2012
- Last updated
- 3 Jan 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided: As per Spanish local regulations
Publications
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.
PubMed 29794066
Study at a glance
From the registry record, last updated by the sponsor on 3 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01567488
- Acronym / sponsor ID
- EVERLAR / GETNE 1003
- Conditions
- Gastrointestinal Neoplasms
- Keywords
- Advanced, Non functioning, Well differentiated
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Grupo Espanol de Tumores NeuroendocrinosUniversity, hospital or other
- Study start
- 8 Jun 2011 (actual)
- Primary completion
- 1 Sep 2014 (actual)
- Study completion
- 7 Jun 2017 (actual)
- First posted
- 30 Mar 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Everolimus + Octreotide LAR treatment | Experimental | Drug: Everolimus, Drug: octreotide LAR |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EverolimusAlso: AfinitorEverolimus 10mg/day | Drug | Everolimus + Octreotide LAR treatment |
| octreotide LARAlso: Sandostatin LAR30 mg each 28 days | Drug | Everolimus + Octreotide LAR treatment |
Primary outcome
Percentage of patients with progression-free survival (PFS)
Time frame: After 12 month of study treatment
Rate of patients
5 secondary outcomes
Number of patients positive for insulin like growth factor 1 receptor (IGF1R) and ribosomal kinase S6 (S6K) phosphorylation.
Time frame: At baseline
Rate of patients with objective responses
Time frame: Each three cycles
Median and average of time for Overall survival
Time frame: At the end of the study
Rate of patients with an early decrease of chromogranin A (CgA) levels
Time frame: Each cycle
Percentage of patients with Adverse Events
Time frame: Each cycle
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jan 2018.
- Derived from this study: PubMed 29794066Capdevila 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.
- Individual participant dataSharing planned: Undecided. As per Spanish local regulations
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ramón Salazar, MD, PhD study chair
Grupo Espanol de Tumores Neuroendocrinos
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Everolimus and octreotide LAR in people with Gastrointestinal Neoplasms, run by Grupo Espanol de Tumores Neuroendocrinos at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of patients with progression-free survival (PFS) (time frame: After 12 month of study treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01567488, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jan 2018.