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Advanced Gastric or EGJ CancerPhase 2/3RAMIRISNCT03081143

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

A Phase 2/3 study testing FOLFIRI, Ramucirumab and Paclitaxel in people with Advanced Gastric or EGJ Cancer, run by Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest at 16 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Gastric or EGJ Cancer
What is being tested?
FOLFIRI, Ramucirumab and Paclitaxel
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
429 participants
Where
16 sitesin 3 countries
Study dates
10 May 2017to 4 May 2026
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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
  • Serum creatinine ≤ 1.5 x upper limit of normal, or creatinine clearance (measured via 24-hour urine collection) ≥40 mL/minute (that is, if serum creatinine is >1.5 times the ULN, a 24-hour urine collection to calculate creatinine clearance must be performed)
  • Urinary protein ≤1+ on dipstick or routine urinalysis (UA; if urine dipstick or routine analysis is ≥2+, a 24-hour urine collection for protein must demonstrate <1000 mg of protein in 24 hours to allow participation in this protocol)
  • Adequate coagulation function as defined by International Normalized Ratio (INR) ≤ 1.5, and a partial thromboplastin time (PTT) ≤ 5 seconds above the ULN (unless receiving anticoagulation therapy). Patients receiving warfarin/ phenprocoumon must be switched to low molecular weight heparin and have achieved stable coagulation profile prior to first dose of protocol therapy.
  • Ability to comply with scheduled assessments and with management of toxicities

Who cannot join

  • Other tumor type than adenocarcinoma (e.g. leiomyosarcoma, lymphoma) or a second cancer except in patients with squamous or basal cell carcinoma of the skin or carcinoma in situ of the cervix that has been effectively treated. Patients curatively treated and disease-free for at least 5 years will be discussed with the sponsor before inclusion
  • 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
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  • 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
  • The patient has uncontrolled or poorly-controlled hypertension (>160 mmHg systolic or > 100 mmHg diastolic for >4 weeks) despite standard medical management
  • Active uncontrolled infection
  • Current history of chronic diarrhea
  • Active disseminated intravascular coagulation
  • Any other serious concomitant disease or medical condition that in the judgment of the investigator renders the subject at high risk of treatment complication or reduced the probability of assessing clinical effect
  • Known Dihydropyrimidine dehydrogenase (DPD) deficiency
  • Prior history of GI perforation/fistula (within 6 months of first dose of protocol therapy) or risk factors for perforation.
  • Serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to first dose of protocol therapy
  • The patient is receiving chronic antiplatelet therapy, including aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs, including ibuprofen, naproxen, and others), dipyridamole or clopidogrel, or similar agents. Once-daily aspirin use (maximum dose 325 mg/day) is permitted
  • Concurrent treatment with other experimental drugs or participation in another clinical trial with any investigational drug within 30 days prior to treatment start or at the same time as this study
  • Lack of resolution of all toxic effects (excluding alopecia) of prior chemotherapy, prior radiotherapy or surgical procedure to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade < 1. Note: Neuropathy due to prior chemotherapy is allowed if not > NCI Grade II according to CTCAE version 4.03
  • Subject pregnant or breast feeding, or planning to become pregnant within 3 months after the end of treatment
  • Subject (male or female) is not willing to use highly effective methods of contraception (per institutional standardCTFG-Guideline) during treatment and for 3 months (male or female) after the end of treatment
  • Patients known to have a HER 2 positive Cancer who have not been treated already with a HER 2 targeting agent.
  • Patients with a psychiatric illness or patients imprisoned or working in the institution of the treating physician.

Trial locations and contacts

16 sites in 3 countries.

16 sites in 3 countries

Germany12 sites

  • HELIOS Klinikum Bad Saarow

    Bad Saarow

  • Charité - Universitätsmedizin Berlin

    Berlin

  • HELIOS Klinikum Berlin Buch

    Berlin

  • Klinikum Bielefeld Mitte

    Bielefeld

  • Kliniken Essen Mitte

    Essen

  • Krankenhaus Nordwest

    Frankfurt

  • Hämatologisch-Onkologische Praxis Eppendorf (HOPE)

    Hamburg

  • Ortenau Klinikum

    Lahr

  • Universitäres Krebszentrum Leipzig

    Leipzig

  • Technische Universität München

    München, 81675

  • Universitätsklinikum Tübingen

    Tübingen

  • Universitätsklinikum Ulm

    Ulm

Other trials in Germany

Austria3 sites

  • Ordensklinikum Linz GmbH, Barmherzige Schwestern

    Linz, Upper Austria, 4010

  • Landeskrankenhaus Feldkirch - Rankweil

    Rankweil, Vorarlberg, 6830

  • Wiener Neustadt, Landesklinikum

    Wiener Neustadt, 2700

Other trials in Austria

Italy1 site

  • U.O. Oncologia Medica, Università Cattolica Sacro Cuore

    Rome

Other trials in Italy

About this study

Official title: 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

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).

Being tested
FOLFIRI, Ramucirumab, Paclitaxel

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FOLFIRIDrug

    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

  • RamucirumabDrug

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

  • PaclitaxelDrug

    80 mg/m2 on day 1, 8, 15

Study groups in NCT03081143
Study groupRoleWhat they receive
FOLFIRI plus RamucirumabExperimentalRamucirumab 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)
Receives: Drug: FOLFIRI; Drug: Ramucirumab
Paclitaxel plus RamucirumabActive comparatorRamucirumab 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
Receives: Drug: Ramucirumab; Drug: Paclitaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 6 months after randomization

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

    duration from date of randomization to death

    Measured: from date of randomization to 1 year after end of treatment

  3. 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

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

Secondary outcomes (5)

  1. Progression-free survival

    duration from the first study drug administration to the first documented evidence of disease progression or death

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

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

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

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

  3. Disease control rate (CR + PR + SD)

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

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

  4. incidence and severity of adverse events according to CTC criteria

    incidence and severity of adverse events according to CTC criteria

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

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

    quality of life scores according to validated questionnaire EORTC-QLQ-C30

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Mar 2017
  2. Study start10 May 2017
  3. Primary completion4 May 2026
  4. Study completion4 May 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
429 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03081143
Sponsor's protocol ID
RAMIRIS
Other IDs
AIO-STO-0415
Acronym
RAMIRIS
Status last verified
Jun 2026
First submitted
6 Mar 2017
Last updated
2 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: No IPD will be shared.

Publications

  • 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.

    PubMed 35202974

  • 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.

    PubMed 37337155

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing FOLFIRI, Ramucirumab and Paclitaxel in people with Advanced Gastric or EGJ Cancer, run by Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest at 16 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in Germany, Austria, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

OS Rate at 6 months primary endpoint for phase II (time frame: 6 months after randomization). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03081143, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2026; AzTrials last refreshed its copy on 26 Oct 2026.

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