Patient case (clinical description): A 63-year-old man comes to the clinic for recent unintentional weight loss. The patient also has epigastric discomfort after meals. He has no known medical problems and takes no medications. His blood pressure is 130/75 and pulse rate is 88/min. He is not febrile. Upper endoscopy shows a lesion in the stomach that shows typical features of diffuse-type adenocarcinoma presenting with signet ring cells that do not form glands.

Patient's own account: I went to the clinic because I had been losing so much weight that it was concerning. I'm a 63-year-old guy, and it is something rather unusual. I'm always suffering from stomachache after every meal. I've never been sick, and I don't take any medicine. The doctor took my blood pressure and told me it was 130/75, and my pulse rate was 88/min. I'm not febrile! I also had to do an endoscopy, and they found a lesion in my stomach that shows typical features of stomach cancer. I'm totally devastated...

Clinical trial: FLOT vs. FLOT/Ramucirumab for Perioperative Therapy of Gastric or GEJ Cancer (RAMSES)

Eligibility criteria:
Inclusion Criteria:

          1. Histologically confirmed, resectable adenocarcinoma of the gastroesophageal junction
             (AEG/GEJ-type II-III) or the stomach (uT2, uT3, uT4, any N category, M0), or any T N+
             M0 patient, with the following specifications:

               1. Medical and technical operability, according to the techniques described in
                  Chapter 12 Surgical Therapy that are subtotal, total or transhiatal extended
                  gastrectomy (patients planned to receive transthoracic esophagectomy are not
                  eligible for the study)

               2. Participating sites in PETRARCA study: Negative HER-2 detection (score IHC HER-2
                  0 or IHC HER-2 1+ ); IHC HER-2 2+ and negative by FISH, SISH or CISH1

          2. No preceding cytotoxic or targeted therapy

          3. No prior partial or complete tumor resection

          4. Female and male patients ≥ 18 and ≤ 70 years. Patients in reproductive age must be
             willing to use adequate contraception during the study and for 7 months after the end
             of ramucirumab treatment (Appropriate contraception is defined as surgical
             sterilization (e.g., bilateral tubal ligation, vasectomy), hormonal contraception
             (implantable, patch, oral), and double-barrier methods (any double combination of:
             IUD, male or female condom with spermicidal gel, diaphragm, sponge, cervical cap)).
             Female patients with childbearing potential need to have a negative pregnancy test
             within 7 days before study start.

          5. ECOG ≤ 1

          6. Exclusion of distant metastasis by CT or MRI of abdomen, pelvis, and thorax, bone scan
             or MRI (if bone metastases are suspected due to clinical signs). Exclusion of the
             infiltration of any adjacent organs or structures by CT or MRI.

          7. Laparoscopic exclusion of peritoneal carcinomatosis, in case of ascites, peritoneal
             masses, or if otherwise suspected clinically

          8. Adequate hematological, hepatic and renal function parameters:

               1. Leukocytes ≥ 3000/mm³, platelets ≥ 100,000/mm³, neutrophil count (ANC) ≥1000/µL,
                  hemoglobin ≥9 g/dL (5.58 mmol/L),

               2. 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 randomization.

               3. Serum creatinine ≤ 1.5 x upper limit of normal

               4. 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).

               5. Bilirubin ≤ 1.5 x upper limit of normal, AST and ALT ≤ 3.0 x upper limit of
                  normal, alkaline phosphatase ≤ 6 x upper limit of normal

          9. Patient able and willing to provide written informed consent and to comply with the
             study protocol and with the planned surgical procedures

        Exclusion Criteria:

          1. Known hypersensitivity against ramucirumab, 5-FU, leucovorin, oxaliplatin, or
             docetaxel

          2. Other known contraindications against ramucirumab, 5-FU, leucovorin, oxaliplatin, or
             docetaxel

          3. Patients with esophageal cancer and those with adenocarcinoma of GEJ type I and all
             patients who are planned to have transthoracic esophagectomy.

          4. Clinically significant active coronary heart disease, cardiomyopathy or congestive
             heart failure, peripheral artery occlusive disease (PAOD, German pAVK), or any history
             of aortic aneurysm

          5. Any arterial thromboembolic events, including but not limited to myocardial
             infarction, transient ischemic attack, cerebrovascular accident, or unstable angina.

          6. Uncontrolled or poorly-controlled hypertension (>160 mmHg systolic or > 100 mmHg
             diastolic for >4 weeks) despite standard medical management.

          7. Clinically significant valvular defect

          8. Past or current history of other malignancies not curatively treated and without
             evidence of disease for more than 5 years, except for curatively treated basal cell
             carcinoma of the skin and in situ carcinoma of the cervix

          9. Criteria of unresectability, e.g.:

               -  Radiologically documented evidence of major blood vessel invasion or encasement
                  by cancer.

               -  Patients with involved retroperitoneal (e.g. para-aortal, paracaval or
                  interaortocaval lymph nodes) or mesenterial lymph nodes (distant metastases!)

         10. Known brain metastases

         11. Other severe internal disease or acute infection

         12. Peripheral polyneuropathy ≥ NCI Grade II

         13. Chronic inflammatory bowel disease

         14. Grade 3-4 GI bleeding within 3 months prior to enrollment.

         15. History of gastric perforation or fistulae in past 6 months

         16. Serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to
             enrollment.

         17. The patient has undergone major surgery within 28 days prior to enrollment except
             staging laparoscopy.

         18. Receiving chronic antiplatelet therapy, including aspirin (Once-daily aspirin use
             (maximum dose 325 mg/day) is permitted), nonsteroidal anti-inflammatory drugs
             (including ibuprofen, naproxen, and others), dipyridamole or clopidogrel, or similar
             agents.

         19. 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.

         20. Cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) and a
             history of hepatic encephalopathy or ascites.

         21. On-treatment participation in another clinical study in the period 30 days prior to
             inclusion and during the study

         22. Subject pregnant or breast feeding, or planning to become pregnant within 7 months
             after the end of treatment.

         23. Patients in a closed institution according to an authority or court decision (AMG §
             40, Abs. 1 No. 4)

         24. Any other concurrent antineoplastic treatment including irradiation

         25. Current chronic alcohol, nicotine or drug abuse or history of chronic alcohol abuse
             during last 12 months. Nicotine abuse is defined as ≥ 25 pack-years (Willigendael et
             al., 2004).
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.
Subject must be at most 70 Years

Eligibility (NLI label): Entailment