Ramucirumab Plus FOLFIRI Versus Ramucirumab Plus Paclitaxel in Patients With Advanced or Metastatic Gastric Cancer, Who Failed One Prior Line of Palliative Chemotherapy

NCT03081143 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: RAMIRISAIO-STO-0415
• Study Type: interventional
• Target: 429
• Locations: 3 countries
• Sites: 16

Brief Summary

This clinical trial will evaluate whether it is beneficial in terms of prolongation of survival to combine FOLFIRI (standard treatment) with ramucirumab compared to the standard treatment of ramucirumab plus paclitaxel in patients with advanced gastric cancer after failure of one prior line of palliative chemotherapy. This trial aims to investigate the efficacy and safety of ramucirumab plus FOLFIRI (investigational arm A) compared to paclitaxel plus ramucirumab (control arm B).

Conditions

Advanced Gastric or EGJ Cancer

Outcome Measures

Primary Outcomes (3)

• OS Rate at 6 months primary endpoint for phase II

  OS Rate at 6 months is defined at the proportion of patients being known to be alive at 6 months after randomisation

  6 months after randomization

• overall survival (OS) co-primary endpoint for phase III

  duration from date of randomization to death

  from date of randomization to 1 year after end of treatment

• Objective Overall Response Rate (ORR) co-primary endpoint for phase III

  proportion of patients with complete or partial response (CR + PR) according to RECIST 1.1

  from randomization for the time of treatment with a maximum of 1 year

Secondary Outcomes (5)

• Progression-free survival

  from date of first study drug administration to up to 1 year after study completion

• Overall response rate (CR + PR) - endpoint for phase II

  from randomization for the time of treatment with a maximum of 1 year

• Disease control rate (CR + PR + SD)

  from randomization for the time of treatment with a maximum of 1 year

• incidence and severity of adverse events according to CTC criteria

  from randomization until 30 days after the last dose of study drug

• Patient reported outcomes: quality of life according to questionnaire EORTC-QLQ-C30

  from randomization until 30 days after the last dose of study drug

Study Arms (2)

FOLFIRI plus Ramucirumab

EXPERIMENTAL

Ramucirumab 8 mg/kg i.v. infusion on day 1 and 15 of a 28-day cycle plus FOLFIRI (Irinotecan 180 mg/m2; i.v. bolus of 5-FU 400 mg/m2, i.v. infusion of leucovorin 400 mg/m2 , followed by a 46-hour continuous administration of 5-FU 2400 mg/m2 on day 1 and 15 of a 28-day cycle)

Drug: FOLFIRI; Drug: Ramucirumab

Paclitaxel plus Ramucirumab

ACTIVE COMPARATOR

Ramucirumab 8 mg/kg i.v. infusion on day 1 and 15 of a 28-day cycle plus Paclitaxel 80 mg/m2 on day 1, 8, 15

Drug: Ramucirumab; Drug: Paclitaxel

Interventions

FOLFIRI DRUG

Irinotecan 180 mg/m2; i.v. bolus of 5-FU 400 mg/m2, i.v. infusion of leucovorin\* 400 mg/m2 , followed by a 46-hour continuous administration of 5-FU 2400 mg/m2 on day 1 and 15 of a 28-day cycle

FOLFIRI plus Ramucirumab

Ramucirumab DRUG

8 mg/kg i.v. infusion on day 1 and 15 of a 28-day cycle

FOLFIRI plus Ramucirumab; Paclitaxel plus Ramucirumab

Paclitaxel DRUG

80 mg/m2 on day 1, 8, 15

Paclitaxel plus Ramucirumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent
• Male or female\* ≥ 18 years of age; Patients in reproductive age must be willing to use adequate contraception (that results in a failure rate of \<1% per year) during the study and for 3 months after the end of ramucirumab treatment (appropriate contraception is defined as surgical sterilization (e.g. bilateral tubal ligation, vasectomy), hormonal contraception (including oral contraceptive pills (combination of estrogen and progesterone), vaginal ring, injectables, implants, intrauterine devices (IUDs) and intrauterine hormone-releasing system (IUS)), nonhormonal IUDs and complete abstinence). Female patients with childbearing potential need to have a negative pregnancy test within 7 days before study start.
• Histologically proven gastric adenocarcinoma including adenocarcinoma of the esophagogastric junction
• Metastatic or locally advanced disease, not amenable to potentially curative resection
• Phase II only: Documented objective radiological or clinical disease progression during or within 6 months of the last dose of first-line platinum and fluoropyrimidine doublet with or without anthracycline or docetaxel. Neoadjuvant/adjuvant treatment is not counted unless progression occurs \<6 months after completion of the treatment. In these cases neoadjuvant/adjuvant treatment is counted as one line.
• OR Phase III only: Radiological or clinical disease progression during or after the last dose of a first-line platinum, fluoropyrimidine-containing therapy. Patients must also have received a taxane with the first-line or during their adjuvant or neoadjuvant therapy or both. Neoadjuvant/adjuvant platinum containing therapy is permitted and is counted as first-line therapy if progression occurs \<12 months after completion of the treatment. If progression occurred ≥ 12 months after completion of neoadjuvant/adjuvant therapy, the therapy is not counted as a treatment line. At decision of the investigator, different regimens can be considered as one line of prior treatment, in case these were administrated as a sequential or alternating therapy.
• Measurable or non-measurable but evaluable disease
• ECOG performance status 0-1
• Life expectancy \> 12 weeks
• Adequate hematological, hepatic and renal functions:
• Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L
• Platelets ≥ 100 x 10\^9/L
• Hemoglobin ≥9 g/dL (5.58 mmol/L)
• Total bilirubin ≤ 1.5 times the upper normal limit (UNL)
• AST (SGOT) and ALT (SGPT) ≤ 2.5 x UNL in absence of liver metastases, or ≤ 5 x UNL in presence of liver metastases; AP ≤ 5 x UNL

You may not qualify if:

• Squamous gastric cancer
• Concurrent chronic systemic immune therapy, chemotherapy, or hormone therapy not indicated in the study protocol
• Phase II only: Previous therapy with paclitaxel or FOLFIRI Phase III only: Previous therapy with FOLFIRI
• Current treatment with any anti-cancer therapy ≤ 2 weeks prior to study treatment start unless rapidly progressing disease is measured
• Concurrent treatment with any other anti-cancer therapy
• Previous exposure to a VEGF or VEGFR inhibitor or any antiangiogenic agent, or prior enrolment in this study
• Patient has undergone major surgery within 28 days prior to first dose of protocol therapy, or minor surgery/subcutaneous venous access device placement within 7 days prior to first dose of protocol therapy. The patient has elective or planned major surgery to be performed during the course of the clinical trial
• Grade 3-4 GI bleeding within 3 months prior to enrollment
• History of deep vein thrombosis (DVT), pulmonary embolism (PE), or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered "significant") during the 3 months prior to first dose of protocol therapy
• Cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) and a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis.
• The patient has uncontrolled known brain or leptomeningeal metastases
• Known allergic/ hypersensitivity reaction to any of the components of the treatment
• Contraindications to the use of atropine
• Other serious illness or medical conditions within the last 12 months prior to study drug administration
• Any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to first dose of protocol

Sponsors & Collaborators

• Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest: lead

Study Sites (16)

Ordensklinikum Linz GmbH, Barmherzige Schwestern

Linz, Upper Austria, 4010, Austria

Location

Landeskrankenhaus Feldkirch - Rankweil

Rankweil, Vorarlberg, 6830, Austria

Location

Wiener Neustadt, Landesklinikum

Wiener Neustadt, 2700, Austria

Location

HELIOS Klinikum Bad Saarow

Bad Saarow, Germany

Location

Charité - Universitätsmedizin Berlin

Berlin, Germany

Location

HELIOS Klinikum Berlin Buch

Berlin, Germany

Location

Klinikum Bielefeld Mitte

Bielefeld, Germany

Location

Kliniken Essen Mitte

Essen, Germany

Location

Krankenhaus Nordwest

Frankfurt, Germany

Location

Hämatologisch-Onkologische Praxis Eppendorf (HOPE)

Hamburg, Germany

Location

Ortenau Klinikum

Lahr, Germany

Location

Universitäres Krebszentrum Leipzig

Leipzig, Germany

Location

Technische Universität München

München, 81675, Germany

Location

Universitätsklinikum Tübingen

Tübingen, Germany

Location

Universitätsklinikum Ulm

Ulm, Germany

Location

U.O. Oncologia Medica, Università Cattolica Sacro Cuore

Rome, Italy

Location

Related Publications (2)

• Lorenzen S, Thuss-Patience P, Pauligk C, Gokkurt E, Ettrich T, Lordick F, Stahl M, Reichardt P, Sokler M, Pink D, Probst S, Hinke A, Goetze TO, Al-Batran SE. FOLFIRI plus ramucirumab versus paclitaxel plus ramucirumab as second-line therapy for patients with advanced or metastatic gastroesophageal adenocarcinoma with or without prior docetaxel - results from the phase II RAMIRIS Study of the German Gastric Cancer Study Group at AIO. Eur J Cancer. 2022 Apr;165:48-57. doi: 10.1016/j.ejca.2022.01.015. Epub 2022 Feb 21.

  PMID: 35202974 RESULT

• Lorenzen S, Schwarz A, Pauligk C, Goekkurt E, Stocker G, Knorrenschild JR, Illerhaus G, Dechow T, Moehler M, Moulin JC, Pink D, Stahl M, Schaaf M, Goetze TO, Al-Batran SE. Ramucirumab plus irinotecan / leucovorin / 5-FU versus ramucirumab plus paclitaxel in patients with advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction, who failed one prior line of palliative chemotherapy: the phase II/III RAMIRIS study (AIO-STO-0415). BMC Cancer. 2023 Jun 19;23(1):561. doi: 10.1186/s12885-023-11004-z.

  PMID: 37337155 DERIVED

MeSH Terms

Interventions

IFL protocol; Ramucirumab; Paclitaxel

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Salah-Eddin Al-Batran, Prof

  Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2017
• First Posted: March 16, 2017
• Study Start: May 10, 2017
• Primary Completion: May 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 14, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

AU (3); IT (1); DE (12)