advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction MedDRA version: 21.1 Level: PT Classification code 10063916 Term: Metastatic gastric cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.1 Level: PT Classification code 10062878 Term: Gastrooesophageal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Cyramza
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: ramucirumab
CAS Number: 947687-13-0
Other descriptive name: RAMUCIRUMAB
Concentration unit: mg/kg m
Sponsors
Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed written informed consent 2. 2. 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 12 weeks 9. Adequate hematological, hepatic and renal functions: • Absolute neutrophil count (ANC) = 1.5 x 109/L • Platelets = 100 x 109/L • Hemoglobin =9 g/dL (5.58 mmol/L) • Total bilirubin = 1.5 times the upper normal limit (UNL) • AST (SGOT) and ALT (SGPT) = 3.0 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
Exclusion criteria
Exclusion criteria: Patients with any of the following will not be eligible for participation: 1. 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 2. Squamous gastric cancer 3. Concurrent chronic systemic immune therapy, chemotherapy, or hormone therapy not indicated in the study protocol 4. Phase II only: Previous therapy with paclitaxel or FOLFIRI Phase III only: Previous therapy with FOLFIRI 5. Current treatment with any anti-cancer therapy = 2 weeks prior to study treatment start unless rapidly progressing disease is measured 6. Concurrent treatment with any other anti-cancer therapy 7. Previous exposure to a VEGF or VEGFR inhibitor or any antiangiogenic agent, or prior enrolment in this study 8. 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 9. Grade 3-4 GI bleeding within 3 months prior to enrollment 10. 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 11. 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. 12. The patient has uncontrolled known brain or leptomeningeal metastases 13. Known allergic/ hypersensitivity reaction to any of the components of the treatment 14. Contraindications to the use of atropine 15. Other serious illness or medical conditions within the last 12 months prior to study drug administration 16. 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 17. The patient has uncontrolled or poorly-controlled hypertension (>160 mmHg systolic or > 100 mmHg diastolic for >4 weeks) despite standard medical management 18. Active uncontrolled infection 19. Current history of chronic diarrhea 20. Active disseminated intravascular coagulation 21. 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 22. Known Dihydropyrimidine dehydrogenase (DPD) deficiency 23. Prior history of GI perforation/fistula (within 6 months of first dose of protocol therapy) or risk factors for perforation. 24. Serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to first dose of protocol therapy 25. 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 d
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Main Objectives for the phase III part of the study: •To compare overall survival (OS) in patients with locally advanced, inoperable or metastatic esophagogastric adenocarcinoma receiving FOLFIRI with ramucirumab versus paclitaxel with ramucirumab as second line therapy in patients who failed prior taxane-containing therapy in the intent to treat population (ITT) and where OS is defined as the time from randomization to death from any cause •To compare Objective Overall Response Rate (ORR) in the groups as described above and where ORR is defined as the proportion of patients with complete or partial remission according to RECIST 1.1 Main Objective for phase II part of the study: OS rate after 6 months, based on an ITT population. ;Secondary Objective: Secondary Objectives for the phase III part of the trial: To compare the treatment arms in terms of •Disease Control Rate (DCR) as defined as proportion of patients with complete or partial remission or stable disease (CR, PR, SD) according to RECIST 1.1 •Progression free survival (PFS) defined as the time from randomization to disease progression or death from any cause •Quality of life (QoL) as measured by EORTC-QLQ-C30 during treatment and follow-up (until d30 after EOT) and/or until progression, or start of new anticancer therapy. Safety Objective for phase II and III: •To evaluate the safety and tolerability of ramucirumab plus FOLFIRI or paclitaxel Secondary Objectives for the phase II part of the study: To compare treatment arms with respect to •Progression-free survival •Objective response rate (CR + PR) •Tumor control rate (CR, PR, SD) •Assessment of quality of life during treatment and follow-up.;Primary end point(s): Primary endpoint for phase II: OS rate after 6 months, based on an ITT population. The experimental therapy (FOLFIRI + Ramucirumab) would be considered to be a highly promising candidate for further development (e.g. in a phase III trial), if the true OS rate amounted to | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): phase II: To compare treatment arms with respect to • Progression-free survival • Objective response rate (CR + PR) • Tumor control rate (CR, PR, SD) • Safety (according to NCI-CTCAE V 4.03) and tolerability • Assessment of quality of life during treatment and follow-up. phase III: • Disease Control Rate (DCR), defined as the proportion of patients with complete or partial remission or stable disease according to RECIST 1.1 • Progression free survival (PFS) defined as time from randomization to disease progression or death from any cause • Safety in terms of AEs as determined by CTCAE version 4.03 and SAEs, discontinuation rate, dose adjustment rate and tolerability • Assessment of quality of life, during treatment and follow-up (until d30 after EOT) and/or until progression.or start of new anticancer therapy. ;Timepoint(s) of evaluation of this end point: Progression-free survival: continuously, tumor assessment every 8 weeks Objective response rate (CR + PR): every 8 weeks Tumor/disease control rate (CR, PR, SD): every 8 weeks Assessment of quality of life: every 4 weeks Safety: continuously during treatment phase and up to 30 days after last treatment | — |
Countries
Austria, Germany, Italy
Contacts
Public ContactStudy Coordination
Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Outcome results
None listed