DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more

Efficacy and Safety of Everolimus and (STZ-5FU) Given One Upfront the Other Upon Progression in Advanced pNET

Information source: Grupo Espanol de Tumores Neuroendocrinos
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Pancreatic Neuroendocrine Tumours.

Intervention: Drug: Everolimus (Drug); STZ-5FU (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Grupo Espanol de Tumores Neuroendocrinos

Official(s) and/or principal investigator(s):
Salazar Ramon, MD, PhD, Principal Investigator, Affiliation: Instituto Catalán de Oncologia, ICO-Hospitalet

Overall contact:
Cristina Vidal, BSc, PhD, Phone: +34932134478, Email: cvidal@meedsamdaims.com


The purpose of this study is to elucidate which sequence of streptozotocin (STZ) based chemotherapy and the mammalian Target of Rapamycin (mTOR) inhibitor, everolimus, gives better results in terms of second Progression Free Survival (PFS) in well differentiated and advanced pancreatic NETs.

Clinical Details

Official title: Randomized Open Label Study to Compare the Efficacy and Safety of Everolimus Followed by Chemotherapy With Streptozotocin- Fluorouracilo (STZ-5FU) Upon Progression or the Reverse Sequence, in Advanced Progressive Pancreatic NETs (pNETs)

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Second Progression Free Survival (second PFS)

Secondary outcome:

Adverse events

Time to first progression

Ratio of incremental cost-efficacy (ICER)

Response Rate (RR)

Early Biochemical response

Time to second progression

Detailed description: STZ based chemotherapy, STZ-5FU, is the actual standard of care for advanced pancreatic Neuroendocrine tumours (pNETS) in the European Union. Everolimus has been recently approved for its use in advanced pNETs by the Food and Drug Administration (FDA) and in Europe by the European Medical Agency (EMA). A randomized study is needed to have a clear knowledge about the best sequence for its administration; this is, before or after palliative chemotherapy. There may or may not be any benefits from giving first each other treatment of the study. The information obtained from this study will help the physician improve the treatment and management of patients with advanced pNET.


Minimum age: 18 Years. Maximum age: 94 Years. Gender(s): Both.


Inclusion Criteria:

- Histologically proven diagnosis of unresectable or metastatic, advanced pancreatic


- Documented confirmation of pancreatic NET G1 or G2 as per European Neuroendocrine

Society (ENETS) classification system.

- Patients from whom a paraffin-embedded primary tumour or metastasis block is

available and sent by Courier.

- Before study inclusion, patients must show progressive disease documented by

radiology 12 months prior to study inclusion. Naive patients can be also included if the patient needs active treatment with either chemotherapy or everolimus.

- Presence of measurable disease as per Response Evaluation Criteria in Solid Tumors

(RECIST) criteria 1. 0, documented by a Triphasic Computed Tomography (CT) scan or multiphase MRI radiological assessment.

- Previous treatment with somatostatin (SS) analogues is allowed. Only those patients

with active functioning syndrome at entry can continue with SS analogues during the study.

- Adequate bone marrow and renal functions, and serum fasting cholesterol

- Women with child-bearing potential must have a negative serum pregnancy test.

- Written Informed Consent obtained according to local regulations

Exclusion Criteria:

- Previous treatment with chemotherapy and/or mTOR inhibitors or tyrosine kinase


- Immune therapy or radiation therapy within 4 weeks prior to the patient entering the


- Hepatic artery embolization within the last 6 months (1 month if there are other

sites of measurable disease), or cryoablation/radiofrequency ablation of hepatic metastasis within 2 months of enrolment.

- Previous treatment with Peptide-Receptor Radionuclide Therapy (PRRT) within the last

6 months and/or without progression following PRRT.

- Uncontrolled diabetes mellitus.

- Any severe and/or uncontrolled medical conditions.

- Treatment with potent inhibitors or inducers of Cytochrome P450 3A4 (CYP3A) isoenzyme

within 5 days immediately before the start of treatment.

- Patients on chronic treatment with corticosteroids or any other immunosuppressive


- Patients known to be HIV seropositive.

- Known intolerance or hypersensitivity to everolimus or its excipients or other

rapamycin analogues. Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

- Known intolerance or hypersensitivity to 5FU or STZ or its excipients.

- Pregnant, lactating women or fertile adults not using effective birth control


- For administrative matters (insurance) patients ≥ 95 are not allowed.

Locations and Contacts

Cristina Vidal, BSc, PhD, Phone: +34932134478, Email: cvidal@meedsamdaims.com

Morten Ladekarl, Aarhus 8000, Denmark; Recruiting

Ulrich Peter Knigge, Copenhagen 2100, Denmark; Recruiting

Lene Vestermark, Odense 5000, Denmark; Recruiting

Denis Smith, Bordeaux 33075, France; Recruiting

Thomas Walter, Lyon 69437, France; Recruiting

Dieter Hörsch, Bad Berka 99437, Germany; Recruiting

Joerg Schrader, Hamburg 20246, Germany; Recruiting

Birgit Cremer, Köln 50937, Germany; Recruiting

Peter Malfertheiner, Magdeburg 39120, Germany; Recruiting

Anja Rinke, Marburg 35033, Germany; Recruiting

Bruno Neu, München 81675, Germany; Recruiting

Christoph Josef Auernhammer, München 81377, Germany; Recruiting

Salvatore Tafuto, Naples 80131, Italy; Recruiting

J. Klumpen, Amsterdam 1105AZ, Netherlands; Recruiting

Jaume Capdevila, Barcelona 08035, Spain; Recruiting

Marta Martin, Barcelona 08025, Spain; Recruiting

Maria Isabel Sevilla, Málaga 29010, Spain; Recruiting

Marta Benavent, Sevilla 41013, Spain; Recruiting

Barbro Eriksson, Upsala 75185, Sweden; Recruiting

Paula Jimenez, Oviedo, Asturias 33006, Spain; Recruiting

Alexander Teule, L'Hospitalet de Llobregat, Barcelona 08908, Spain; Recruiting

Jean-Philippe Metges, Brest, Brest Cedex 29609, France; Recruiting

Philippe Ruszniewski, Clichy, Clichy Cedex 92118, France; Recruiting

Carlo Carnaghi, Rozzano, Milan, Italy; Recruiting

Bernard Goichot, Strasbourg, Strasbourg Cedex 67098, France; Recruiting

Additional Information

Starting date: October 2014
Last updated: June 23, 2015

Page last updated: August 23, 2015

-- advertisement -- The American Red Cross
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017