advanced HER-2 negative gastric or gastroesophageal junction cancers MedDRA version: 21.1 Level: LLT Classification code 10071114 Term: Metastatic gastric adenocarcinoma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: CYRAMZA
Product Name: CYRAMZA
Product Code: [-]
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: RAMUCIRUMAB
CAS Number: 947687-13-0
Current Sponsor code: NA
Sponsors
FONDAZIONE IRCCS "ISTITUTO NAZIONALE DEI TUMORI"
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent prior to performance of any study procedure; 2. Age =18 years; 3. ECOG Performance Status 0-1 (Appendix I); 4. Life expectancy of at least 12 weeks in the opinion of the Investigator; 5. Unresectable locally advanced or metastatic, carcinoma histologically confirmed, HER-2 negative gastric or GEJ cancer with measurable and/or non measurable disease based on RECIST, v1.1. 6. Must have received lead-in chemotherapy in the first-line setting using one of the fluoropyrimidines- and oxaliplatin-based doublet combinations (FOLFOX-4, mFOLFOX-6 and XELOX) and continued for three months (i.e. 6 administrations for 2 weekly cycles regimens or 4 administrations for 3 weekly cycles regimens). Patients who had received adjuvant cisplatin/oxaliplatin plus fluoropyrimidine-based doublet chemotherapy and had recurrence beyond 12 months from its completion are eligible. 7. Must have radiological evidence of clinical benefit following the last dose of the lead-in chemotherapy (either CR, PR or SD by RECIST v1.1 criteria in case of measurable disease, or absence of progressive disease in case of non-measurable disease). 8. Laboratory requirements: a) Neutrophils = 1.0 x 10^9/L, Platelets =100 x 10^9/L, and Haemoglobin = 9 g/dL b) Total bilirubin =1.5 time the upper-normal limits (UNL) of the Institutional normal values; ASAT (SGOT) and/or ALAT (SGPT) =2.5 x UNL, or =5 x UNL in case of liver metastases; alkaline phosphatase = 2.5 x UNL, = 5 x UNL in case of liver metastases, =10 x UNL in case of bone metastases; LDH 50 mL/min or serum creatinine =1.5 x upper limit of normal (ULN) d) International Normalized Ratio (INR) = 1.5 or Prothrombin time (PT) = 1.5 x ULN 9. The patient’s urinary protein is = 1+ on dipstick or routine urinalysis. If urine dipstick or routine analysis indicates proteinuria = 2+, then a 24-hour urine must be collected and must demonstrate =65 years) yes F.1.3.1 Number of subjects for this age range 140
Exclusion criteria
Exclusion criteria: 1.HER2 positive status, or histology of adenosquamous cell origin 2.Prior malignancy, active within 3 years from study entry, except for locally curable cancers that have been apparently cured and need no subsequent therapy, such as non-melanoma skin cancers, superficial bladder cancer or cancer in situ of the breast or cervix. 3.Has a serious illness or medical condition(s) including, but not limited to the following: a. Known brain metastasis or leptomeningeal metastasis. b. Active infection (ie, body temperature =38°C due to infection). c. Ascites, pleural effusion or pericardial fluid requiring drainage in last 4 weeks. d. Intestinal obstruction, pulmonary fibrosis or interstitial pneumonitis, renal failure, liver failure, or cerebrovascular disorder. e. Uncontrolled diabetes. f. The patient has symptomatic congestive heart failure (New York Heart Association II-IV) or symptomatic or poorly controlled cardiac arrhythmia. g. The patient has experienced any arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack, within 6 months prior to randomization. h. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, or hepatitis B or C. i. Autoimmune disorders or history of organ transplantation that require immunosuppressive therapy. l. Psychiatric disease that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results. m. The patient has a history of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered “significant”) during the 3 months prior to randomization. n. The patient is receiving therapeutic anticoagulation with warfarin, low-molecular weight heparin or similar agents. Patients receiving prophylactic, low-dose anticoagulation therapy are eligible provided that the coagulation parameters defined in the inclusion criteria (INR = 1.5 and aPTT = 1.5 x ULN) or (PT = 1.5 x ULN and aPTT =1.5 x ULN) are met. o. The patient is receiving chronic therapy with nonsteroidal anti-inflammatory agents (NSAIDs, eg, indomethacin, ibuprofen, naproxen or similar agents) or other anti-platelet agents (eg, clopidogrel, ticlopidine, dipyridamole, anagrelide). Aspirin use at doses up to 325 mg/day is permitted. p. The patient has significant bleeding disorders, vasculitis, or had a significant bleeding episode from the gastrointestinal tract within 3 months prior to study entry. q. History of gastrointestinal perforation and/or fistulae within 6 months prior to randomization. r. The patient has a bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection (hemicolectomy or extensive small intestine resection with chronic diarrhea), Crohn's disease, ulcerative colitis, or chronic diarrhea. s. The patient has uncontrolled arterial hypertension = 150 / = 90 mm Hg despite standard medical management. t. The patient has a serious or non healing wound or peptic ulcer or bone fracture within 28 days prior to randomization. u. Known allergy or hypersensitivity to monoclonal antibody treatment or any components used in the ramucirumab DP preparation. Known allergy or hypersensitivity to paclitaxel or any components used in the paclitaxel preparation or other contraindication for taxane therapy. v.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare PFS of subjects who receive switch maintenance with ramucirumab plus paclitaxel (arm A) following a first-line chemotherapy doublet combination versus subjects who receive continuation of first-line chemotherapy until progressive disease/unacceptable toxicity/death (arm B). ;Secondary Objective: -To evaluate overall Survival, time-to-treatment failure, overall response rate and duration of response -To compare the percentage of patients that will receive a second line therapy according to arm treatment. -Safety -Quality of life ;Primary end point(s): To compare PFS of subjects who receive switch maintenance with ramucirumab plus paclitaxel (arm A) following a first-line chemotherapy doublet combination versus subjects who receive continuation of first-line chemotherapy until progressive disease/unacceptable toxicity/death (arm B);Timepoint(s) of evaluation of this end point: 6 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall Survival; To compare the percentage of patients that will receive a second line therapy; Safety; Quality of life;Timepoint(s) of evaluation of this end point: 12 months; 12 months; 18 months; 18 months | — |
Countries
Italy
Contacts
Public ContactClinical Trial Center
Fondazione IRCCS Istituto Nazionale Tumori
Outcome results
None listed