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Open Access 01-12-2021 | Ramucirumab | Study protocol

Ramucirumab in combination with dacarbazine in patients with progressive well-differentiated metastatic pancreatic neuroendocrine tumors (RamuNET): study protocol for a multicenter single-arm trial

Authors: Sebastian Krug, Thomas Kegel, Thomas M. Gress, Anja Rinke, Leonidas Apostolidis, Henning Jann, Alexander König, Dieter Hörsch, Jörg Schrader, Thomas J. Ettrich, Michael Richter, Jörg Steighardt, Patrick Michl

Published in: BMC Cancer | Issue 1/2021

Abstract

Background

Cytotoxic chemotherapy combinations and targeted agents represent established treatment concepts in advanced pancreatic neuroendocrine tumors (PNETs). However, response rates, side effects and outcome data strongly vary among these therapeutic approaches. Head-to-head comparisons between chemo- and molecular therapies are missing and secondary resistances frequently occur. The RamuNET trial aims to identify the effectiveness of dual treatment with DTIC and ramucirumab in progressive advanced PNET patients.

Methods

The RamuNET study is an investigator-initiated multicenter prospective single-arm trial to evaluate the efficacy of ramucirumab in combination with dacarbazine (DTIC) over a period of at least 6 months. Patients with progressive well-differentiated and metastatic pancreatic neuroendocrine tumors are eligible. The study aims to include 45 patients over a period of 24 months with a minimum follow-up of 24 months. The primary endpoint is disease control after 6 months. Secondary endpoints include progression-free survival, biochemical response, overall survival, quality of life and toxicity. Based on the hypothesis that 80% of the patients can achieve a disease control after 6 months, the sample size calculation follows an exact binomial single-stage design. H0: p < =p₀ = 60% versus H1: p > =p₁ = 80%, alpha = 0.05, beta = 0.1.

Discussion

This study investigates a new therapeutic approach using the combination of cytotoxic and targeted antiangiogenic therapy in advanced PNET. If positive, this trial will be the basis for a randomized two-arm study to investigate the combination of ramucirumab and DTIC against other established therapies in PNET.

Trial registration

EudraCT: 2017–001207-68. Date of registration: 2018.01.03.

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Title: Ramucirumab in combination with dacarbazine in patients with progressive well-differentiated metastatic pancreatic neuroendocrine tumors (RamuNET): study protocol for a multicenter single-arm trial
Authors: Sebastian Krug
Thomas Kegel
Thomas M. Gress
Anja Rinke
Leonidas Apostolidis
Henning Jann
Alexander König
Dieter Hörsch
Jörg Schrader
Thomas J. Ettrich
Michael Richter
Jörg Steighardt
Patrick Michl
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Ramucirumab
Neuroendocrine Tumor
Cytostatic Therapy
Published in: BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-021-08900-7

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Abstract

Background

Methods

Discussion

Trial registration

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