1502TiP - Paclitaxel + ramucirumab versus paclitaxel alone in patients with squamous-cell carcinoma of the esophagus, refractory or intolerant to combination therapy with fluoropyrimidine and platinum-based drugs - RAMOS, a randomized phase II trial of the German Gastric Group of the AIO

Background

Patients with unresectable locally advanced or metastatic squamous-cell carcinoma of the esophagus (ESCC), refractory or intolerant to first-line combination therapy with Fluoropyrimidine and Platinum-based drugs have limited therapeutic options and a dismal prognosis, with a 5-year survival rate of 10%. Ramucirumab is proven alone or in combination with paclitaxel as second line treatment in advanced gastroesophageal adenocarcinoma. It is anticipated that this combination can also be effective and be safely administered in advanced ESCC. This provides a strong rationale to conduct a randomized phase II study evaluating the efficacy and safety of ramucirumab in combination with paclitaxel as 2^nd-line therapy in patients with advanced ESCC.

Trial design

This is a prospective, multicenter, randomized, investigator-initiated phase II trial. Pts with advanced or metastatic ESCC will be randomized 1:1 to treatment with Paclitaxel 80 mg/m² on day 1, 8, 15 plus Ramucirumab 8 mg/kg i.v. infusion on day 1 and 15 of a 28-day cycle (Arm A) or Paclitaxel alone (Arm B). Primary endpoint of the trial is overall survival rate after 6 months (OS@6) based on the ITT population. Main secondary endpoints are progression-free survival, overall survival, objective response rate, tumor control rate, safety and quality of life (EORTC QLQ-C30). The statistical considerations are solely based on the experimental arm Paclitaxel + Ramucirumab. 186 pts (93 per arm) will be enrolled for testing if the experimental therapy is a highly promising candidate for further development, i.e. if the true OS@6 is 66% or more (corresponding to a median OS of 10 months) or if it is insufficiently active, i.e. if the true OS@6 is 55% or lower. At the date of submission, (May 2020), 7 of planned 186 pts are randomized.

Clinical trial identification

NCT03762564.

Editorial acknowledgement

Legal entity responsible for the study

Institut für Klinische Krebsforschung, IKF GmbH.

Funding

Lilly Deutschland GmbH.

Disclosure

All authors have declared no conflicts of interest.