Abstract 1499TiP
Background
Ramucirumab (Ram) as monotherapy or plus paclitaxel is a proven second-line option for advanced gastroesophageal adenocarcinoma. More and more patients (pts) are pretreated with docetaxel in the perioperative or first-line setting. These pts may benefit more from another, non-cross resistant chemotherapy backbone regimen. The phase II portion of the RAMIRIS trial evaluated the addition of Ram to FOLFIRI and demonstrated feasibility and efficacy of this combination. With preliminary results showing a response rate of 24% and a median PFS of 4.3 months, docetaxel pre-treated pts seemed to derive pronounced benefit from FOLFIRI-Ram. This provided a rationale for continuation the trial as phase III, which enrolls taxane-pretreated pts only and is currently recruiting.
Trial design
This is a prospective, multicenter, randomized, investigator initiated phase II/III trial. Phase II has completed recruitment with 111 enrolled pts. In phase III, 318 taxane-pretreated pts with advanced gastric or esophagogastric junction cancer will be randomized 1:1 to FOLFIRI (irinotecan 180 mg/m2; 5-FU 400 mg/m2; leucovorin 400 mg/m2; 5-FU 2400 mg/m2 on day 1 and 15 of a 28-day cycle) plus ramucirumab 8mg/kg every two weeks (Arm A) or paclitaxel 80 mg/m2 (days 1, 8, 15 of a 28-day cycle) plus ramucirumab 8mg/kg every two weeks (Arm B). Co-primary endpoints are overall survival and objective overall response rate (ORR). Median OS in the standard arm is assumed to be about 6 months. An increase to 8.6 months (corresponding to a hazard ratio of HR = 0.70) in the experimental arm seems to be a reasonable aim, and is unequivocally considered to be a major, clinically relevant advantage. Secondary endpoints are disease control rate, progression-free survival, safety and quality of life as assessed by EORTC-QLQ-C30 questionnaire. By May 2020, a total of 15 pts have been enrolled.
Clinical trial identification
ClinicalTrials.gov: NCT03081143; EudraCT: 2015-005171-24.
Editorial acknowledgement
Legal entity responsible for the study
Institut für Klinische Krebsforschung IKF GmbH.
Funding
Lilly Deutschland GmbH.
Disclosure
S-E. Al-Batran: Advisory/Consultancy, Research grant/Funding (self): Roche ; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Celgene; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Lilly; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (self): Merck; Advisory/Consultancy, Speaker Bureau/Expert testimony: Nordic Bioscience; Advisory/Consultancy: Merck Sharp & Dohme; Speaker Bureau/Expert testimony: AIO gGmbH; Speaker Bureau/Expert testimony: Forum für Medizinische Fortbildung; Speaker Bureau/Expert testimony: MCI group; Shareholder/Stockholder/Stock options: IKF Klinische Krebsforschung; Research grant/Funding (self): Medac; Research grant/Funding (self): Hospira; Research grant/Funding (self): Sanofi; Research grant/Funding (self): German Cancer Aid ; Research grant/Funding (self): German Research Foundation ; Research grant/Funding (self): Federal Ministry of Education and Research ; Research grant/Funding (self): Vifor Pharma. T.O. Götze: Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Advisory/Consultancy: MSD Oncology; Advisory/Consultancy: Bayer; Advisory/Consultancy: Servier; Advisory/Consultancy: Roche; Research grant/Funding (self): Deutsche Forschungsgemeinschaft; Research grant/Funding (self): Gemeinsamer Bundesausschuss. E. Goekkurt: Advisory/Consultancy: MSD; Advisory/Consultancy: Servier ; Advisory/Consultancy: Bristol-Myers Squibb ; Advisory/Consultancy: Roche; Advisory/Consultancy: Sanofi. R.D. Hofheinz: Honoraria (self), Advisory/Consultancy: Merck Serono; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Amge; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Sanofi; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Bristol-Myers Squibb ; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD; Honoraria (self), Speaker Bureau/Expert testimony: Lilly ; Speaker Bureau/Expert testimony: Merck; Speaker Bureau/Expert testimony: SERVIER ; Honoraria (self), Research grant/Funding (institution): Medac; Research grant/Funding (institution): German Cancer Aid. M. Möhler: Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck Serono ; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Amgen ; Honoraria (self), Advisory/Consultancy: Taiho Pharmaceutical; Advisory/Consultancy: Nordic Group; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Yakult Pharmaceutical; Advisory/Consultancy, Travel/Accommodation/Expenses: Roche ; Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy: Servier; Travel/Accommodation/Expenses: Amgen; Travel/Accommodation/Expenses: ASCO; Travel/Accommodation/Expenses: German Cancer Societ; Travel/Accommodation/Expenses: ESMO; Honoraria (self): Lilly/ImClon; Honoraria (self): Roche/Genentech ; Honoraria (self): MSD Oncology ; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): AstraZeneca/MedImmune; Research grant/Funding (institution): Leap Therapeutics; Research grant/Funding (institution): Jennere; Research grant/Funding (institution): AstraZeneca. M. Stahl: Honoraria (self): Celgene; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Travel/Accommodation/Expenses: Merck Serono; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: MSD; Honoraria (self): Pfizer; Honoraria (self): Sanofi; Honoraria (self): Servier; Honoraria (self), Travel/Accommodation/Expenses: Amgen; Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy: Shire. P.C. Thuss-Patience: Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: MSD; Advisory/Consultancy, Research grant/Funding (institution): Merck Serono; Advisory/Consultancy: Roche; Advisory/Consultancy: Lilly; Advisory/Consultancy: Servier. All other authors have declared no conflicts of interest.