Clinical trial: FLOT vs. FLOT/Herceptin/Pertuzumab for Perioperative Therapy of HER-2 Expressing Gastric or GEJ Cancer (NCT02581462)

Eligibility criteria:
Inclusion Criteria:

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

               -  Medical and technical operability

               -  Centralized detection of either an adenocarcinoma with HER-2 3+ (IHC) or HER-2 2+
                  (IHC) with amplification proven by FISH, SISH or CISH

          2. No preceding cytotoxic or targeted therapy

          3. No prior partial or complete tumor resection

          4. Exclusion of the infiltration of any adjacent organs or structures by CT or MRI

          5. Exclusion of distant metastasis by CT or MRI of thorax and abdomen, and bone scan (if
             osseous lesions are suspected due to clinical signs)

          6. Female and male patients ≥ 18 years. Patients in reproductive age must be willing to
             use adequate contraception during the study and for 7 months after the end of
             pertuzumab and Herceptin 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.

          7. ECOG ≤ 2

          8. Laparoscopic exclusion of peritoneal carcinomatosis, if suspected clinically

          9. Adequate haematological, hepatic and renal function parameters:

               -  Leukocytes ≥ 3.000/mm³, platelets ≥ 100.000/mm3

               -  Serum creatinine ≤ 1.5 x upper limit of normal, or GFR > 40 ml/min

               -  Bilirubin ≤ 1.5 x upper limit of normal, AST and ALT ≤ 3.5 x upper limit of
                  normal, alkaline phosphatase ≤ 6 x upper limit of normal

         10. LVEF value > 55 %, as assessed by echocardiography

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

          2. Known hypersensitivity against Herceptin, pertuzumab, 5-FU, leucovorin, oxaliplatin,
             or docetaxel

          3. Other known contraindications against Herceptin, pertuzumab, 5-FU, leucovorin,
             oxaliplatin, or docetaxel

          4. Documented history of congestive heart failure of any NYHA, myocardial infarction
             within the past 6 months before the first dose of study treatment

          5. Clinically significant valvular defect , history of poorly controlled arterial
             hypertension (systolic blood pressure > 180 mmHG or diastolic blood pressure > 100
             mmHg) or uncontrollable high-risk cardiac arrhythmia (i.e tachycardia with a heart
             rate > 100/min at rest), significant ventricular arrhythmia (ventricular tachycardia)
             or higher grade atrioventricular-block (second degree AV-block Type 2 (Mobitz2) or
             third degree AV-block)

          6. 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

          7. Known brain metastases

          8. Other severe internal disease or acute infection

          9. Peripheral polyneuropathy ≥ NCI Grade II

         10. Chronic inflammatory bowel disease

         11. Clinically significant active GI bleeding

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

         13. Subject pregnant or breast feeding, or planning to become pregnant within 6 months
             after the end of treatment.

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

         15. Any other concurrent antineoplastic treatment including irradiation
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 99 Years

Patient description (medical language): 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 description (patient's own words): 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...

Does the patient match the trial criteria? 1