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
Summary
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 eventsTime 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.
Eligibility
Minimum age: 18 Years.
Maximum age: 94 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Histologically proven diagnosis of unresectable or metastatic, advanced pancreatic
NET.
- 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
inhibitors.
- Immune therapy or radiation therapy within 4 weeks prior to the patient entering the
study.
- 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
agent.
- 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
methods.
- 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
|