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 (RAMIRIS)

  • STATUS
    Recruiting
  • End date
    Mar 16, 2025
  • participants needed
    429
  • sponsor
    Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Updated on 16 September 2022

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).

Details
Condition Advanced Gastric or EGJ Cancer
Treatment Paclitaxel, FOLFIRI, Ramucirumab
Clinical Study IdentifierNCT03081143
SponsorInstitut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Last Modified on16 September 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

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
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

Exclusion Criteria

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
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
Current treatment with any anti-cancer therapy ≤ 2 weeks prior to study treatment start unless rapidly progressing disease is measured
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
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
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
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
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