advanced or metastatic adenocarcinoma of the stomach or the 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® 10 mg/ml Konzentrat zur Herstellung einer Infusionslösung
Product Name: Ramucirumab
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: RAMUCIRUMAB
CA
Sponsors
Institut für Klinische Krebsforschung IKF GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed informed consent form. 2. Men or women* = 18 years of age. Patients of reproductive age must be prepared to use a suitable contraceptive method during the study and up to 3 months after the end of ramucirumab treatment. A suitable method of contraception is defined as surgical sterilization (e.g. bilateral fallopian tube ligation, vasectomy), hormonal contraception (implantable, patch, oral), and double barrier methods (each two-fold combination of intrauterine pessary, condom for men, or women with spermicidal gel, diaphragm, contraceptive sponge, cervical cap). Women of child-bearing potential must have a negative pregnancy test within the last 7 days prior to the start of study therapy. *There is no data that indicates a specific gender distribution. Therefore, patients are included regardless of their gender. 3. Histologically proven adenocarcinoma of the stomach, including adenocarcinoma of the gastroesophageal junction (note: previous histological assessment during disease history of patient sufficient, current biopsy during screening for this trial is not mandatory) 4. Documented, objective, radiological or clinical progression of the disease during or within 4-6 weeks after the last dose of a ramucirumab based second-line therapy (ramucirumab monotherapy or a combination of ramucirumab + paclitaxel, respectively ramucirumab + FOLFIRI). 5. Measurable or non-measurable but evaluable disease. 6. ECOG Performance status 0-2. 7. Life expectancy > 8 weeks. 8. Appropriate haematological, hepatic and renal function: a. Absolute number of neutrophils (ANC) = 1.5 x 109/L b. Platelets = 100 x 109/L c. Hemoglobin = 9 g/dL (5.58 mmol/L) d. Total bilirubin = 1.5 times the upper limit of normal (UNL) e. AST (SGOT) and ALT (SGPT) = 2.5 x UNL without existing liver metastases, or = 5 x UNL in the presence of liver metastases; AP = 5 x UNL 9. Serum creatinine = 1.5 x UNL or creatinine clearance (measured by 24h urine) = 40 mL / min (i.e. if the serum creatinine level is > 1.5 x UNL, then a 24h urine test must be performed to check the creatinine clearance to be determined). Protein level in urine = 1+ by dipstick analysis or routine urine measurement (if the dipstick analysis or the routine test = 2+, a subsequent 24h urine protein measurement must show a value of =65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. Presence of tumors other than adenocarcinomas (e.g., leiomyosarcoma, lymphoma) or a secondary tumor other than squamous or basal cell carcinomas of the skin or in situ carcinomas of the cervix which have been effectively treated. The sponsor decides to include patients who have received curative treatment and have been disease-free for at least 5 years. 2. Squamous cell carcinoma of the stomach or gastroesophageal junction. 3. Simultaneous, ongoing, systemic immunotherapy, chemotherapy, or hormone therapy not described in the study protocol. 4. Simultaneous treatment with a different anti-cancer therapy other than that provided for in the study (excluding palliative radiotherapy for symptom control). 5. 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 6. The patient has undergone major surgery within the last 28 days prior to the start of study-specific therapy or has undergone minor surgery within the last 7 days prior to the start of study therapy. The patient had subcutaneous venous access within the last 7 days prior to the start of the study-specific therapy. The patient plans to undergo major surgery while participating in the clinical trial. 7. Gastrointestinal bleeding grade 3-4 within the last 3 months prior to enrollment in the study. 8. History of deep vein thrombosis (DVT), pulmonary embolism (PE), or any other clinically important thromboembolic event during the last 3 months prior to the start of study-specific therapy (thrombosis caused by venous ports, catheters, or superficial venous thrombosis are not considered "clinically meaningful"). 9. Stage B cirrhosis according to Child-Pugh criteria (or worse) or cirrhosis (of any grade) with a history of hepatic encephalopathy or clinically significant ascites resulting from cirrhosis. Clinically significant ascites is defined as ascites resulting from cirrhosis requiring diuretics or paracentesis. 10. Known brain or leptomeningeal metastases. 11. Known allergic / hypersensitive reactions to at least one of the treatment components. 12. Other serious illnesses or medical ailments within the last 12 months prior to the start of the study. 13. Any arterial thromboembolic event which includes, but is not limited to, the following: myocardial infarction, transient ischemic attack, cerebrovascular insult, unstable angina within the last 6 months prior to the initiation of study therapy. 14. Uncontrolled or under-adjusted hypertension (> 160 mmHg systolic or > 100 mmHg diastolic hypertension for more than 4 weeks) despite standard medical treatment. 15. Presence of an active, uncontrollable infection. 16. Chronic inflammatory bowel disease. 17. Active disseminated intravascular coagulation. 18. Any other serious concomitant or medical condition that, in the opinion of the investigator, presents a high risk of complications to the patient or reduces the likelihood of clinical effect. 19. Known dihydropyrimidine dehydrogenase (DPD) deficiency. 20. History of gastrointestinal perforation / fistula (within the last 6 months prior to the start of study-specific therapy) or presence of risk factors favoring perforation. 21. Serious or non-healing wounds, ulcers, or broken bones within the last 28 days prior to the start of study-specific therapy. 22. The patient
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether a combination of ramucirumab, beyond progression after a SOC 2nd line ramucirumab based pre-treatment (Ram beyond progression) in patients with locally advanced or metastatic adenocarcinoma, plus TAS-102 shows good tolerability without safety issues regarding the serious adverse event rate of any cause.;Secondary Objective: To determine whether the combination shows positive signals regarding efficacy in the secondary endpoints (e.g. prolongation of progression-free survival of TAS-102 plus ramucirumab compared with TAS-102 monotherapy - historical data according to TAGS trial).;Primary end point(s): The primary endpoint of the study is tolerability and toxicity, defined by the rate of serious adverse events (SAEs) of any cause according to CTCAE v5.0;Timepoint(s) of evaluation of this end point: The final analysis will be conducted when the last patient reached EOT + 30 days of follow-up and all patients are fully documented. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Rate of treatment-related AEs and SAEs according to CTCAE v5.0 • Rate of grade 3 or worse adverse events for neutropenia • Rate of grade 3 or worse adverse events for anemia • Rate of grade 3 or worse adverse events for leucopenia • Rate of grade 3 or worse adverse events for thrombocytopenia • Frequency of abnormal laboratory parameters • Progression Free Survival (PFS) according to RECIST 1.1 • Objective Response Rate (ORR) • Overall survival (OS) ;Timepoint(s) of evaluation of this end point: Progression free survival Progression free survival (PFS) is defined as the time from enrollment to the first documented evidence of disease progression or death. If no information will be available for the evaluation of progression, patients will be censored at the timepoint of last tumor assessment. Objective response rate Objective response rate is defined as proportion of patients with a best overall response of complete response (CR) or partial response (PR). Tumor response will be evaluated using RECIST 1.1 criteria. Overall survival Overall survival (OS) is defined as the time from enrollment to the date of death from any cause. | — |
Countries
Germany
Contacts
Public ContactClinical Trial Unit
Institut für Klinische Krebsforschung IKF GmbH
Outcome results
None listed