A multicenter phase II study of S-1+ramucirumab as first line treatment in elderly patients with advanced/recurrent gastric cancer(KSCC1701)

JRCT ID: jRCTs071180066

Registered date:20/03/2019

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: gastric cancer
• Date of first enrollment: 16/09/2017
• Target sample size: 48
• Study type: Interventional

Intervention(s)

The protocol treatment used in this study will be S-1+ramucirumab. If either S-1 or RAM will be discontinued in accordance with criteria during administration of the protocol treatment and the remaining medication will be administered alone, this monotherapy will be viewed as the protocol treatment.

1) Medications used
i.Tegafur, gimeracil, and oteracil: S-1
(Trade name: TS-1, S-1KK, EE S-1, NK S-1, S-1 NP, S-1 Meiji, Tenox, Temeral)
ii.Ramucirumab: RAM (Cyramza for intravenous infusion, 100 mg, 500 mg)

2) Medication dose and method of administration
Once a subject is enrolled, CReS Kyushu's Enrollment Allocation System will notify the patient's primary physician of the medication dose (the dose must be confirmed by the patient's primary physician).
i. S-1: A course of treatment will last 42 days.Treatment will continue unless any of the criteria for discontinuation of the protocol treatment,a pause during a course of S-1, or a schedule change (from courses to terms) or for a reduction in dose or discontinuation (of S-1) are met. In accordance with body surface area, S-1 will be administered in a dose of 40-60 mg once after breakfast and once after dinner. S-1 will be orally administered twice a day for 28 days (from after dinner on day 1 to after breakfast on day 29) with a respite of 14 days (starting S-1 administration after breakfast on day 1 or after breakfast on day 2 will not be permitted).
ii. Ramucirumab: Ramucirumab will be intravenously infused in a dose of 8 mg/kg on day 1 of the first course. Subsequent treatment will continue every 2 weeks unless criteria for discontinuation of the protocol treatment, for starting a course (or term) and criteria for administering RAM, or for a reduction in dose or discontinuation (of ramucirumab) are met.

Outcome(s)

• Primary Outcome: 1-year survival rate

Secondary Outcome

Overall survival (OS)
Progression-free survival (PFS)
Response rate (RR)
safety (Safety)

Key inclusion & exclusion criteria

• Age minimum: >= 70age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1) Individuals who have consented in writing.
2) A lead investigator deems that the patient can be treated with the protocol.
3) Patients with gastric cancer that is not amenable to curative surgery or that is recurrent and that has been histopathologically confirmed to be primary adenocarcinoma of the stomach or gastroesophageal junction.
4) Patients with cancer that is HER2-negative (HER2-indeterminate are eligible).
5) Patients who are able to take medication orally.
6) Patients who are age 70 or older when they provide consent.
7) Patients with an ECOG Performance status of 0-1.
8) Criteria prior to treatment
i.Patients who have not previously undergone surgery.
ii.Patients who have previously undergone surgery
A)Patients who underwent a curative resection.
B)Patients who underwent non-curative surgery.
C)Exploratory laparotomy, bypass surgery, etc.
9) The patient has no severe dysfunction of major organs (bone marrow,liver,kidneys,heart,lungs,etc.) and the patient's laboratory results from up to 14 days prior to enrollment meet the following criteria:
i. Neutrophil count>=1,500/mm^3
ii. Platelet count>=100,000/mm^3
iii. Hemoglobin>=9.0 g/dL
iv. Total bilirubin=<1.5 mg/dL
v. AST=<3xULN (A level of =<5xULN is permitted for patients with liver metastasis)
vi. ALT=<3xULN (A level of 5xULN is permitted for patients with liver metastasis)
vii. Albumin>=2.5 g/dL
viii. Dipstick urinalysis results in a reading=<1+ protein.
ix. Creatinine clearance>=40 mL/min
x. Clotting: Patients with appropriate clotting as defined by an international normalized ratio (INR) of 1.5 or less and a partial thromboplastin time (PTT) no more than 5 seconds above the ULN (when not receiving anticoagulant therapy).

Exclude criteria

1)Patients who have severe drug hypersensitivity.
2)Patients who have undergone major surgery up to 28 days prior to enrollment or in whom a central venous access device has been placed up to 7 days prior to the initial treatment. Patients who are scheduled to undergo major surgery during the study period. Patients with a severe hemorrhagic disorder within 12 weeks of enrollment.
3)Patients who have had a gastrointestinal perforation and/or fistula up to 6 months prior to enrollment.
4)Patients with a serious or non-healing wound up to 28 days prior to enrollment.
5)Patients who have had deep vein thrombosis, pulmonary embolism, or some other major form of thromboembolism up to 3 months prior to enrollment.
6)The patient has experienced any arterial thromboembolic events, within 6 months prior to first protocol therapy.
7)Patients receiving chronic administration of a non-steroidal antiinflammatory drug or some other antiplatelet drug.
8)Patients with an active infection.
9)Patients with hypertension (>160 mmHg systolic or > 100 mmHg diastolic for >4 weeks) that cannot be adequately controlled with 2 antihypertensives.
10)Patients with diabetes mellitus that cannot be controlled adequately with medication.
11)Patients with heart disease that may pose a problem.
12)Patients with severe pulmonary disease.
13)Patients with a psychiatric disorder.
14)Patients with active gastrointestinal tract bleeding requiring repeated transfusions.
15)Patients receiving phenytoin, warfarin potassium, or flucytosine.
16)Patients with diarrhea (Grade 2 or worse).
17)Patients with active multiple cancers.
18)Men who wish to conceive with a partner.
19)Patients with hepatic cirrhosis or active hepatitis.
20)Patients with cirrhosis, with a history of hepatic encephalopathy, or with clinically significant ascites.
21)Other patients whom a lead investigator or the patient's primary physician deems are not appropriate for this study.

Related Information

• Primary Sponsor: Suyama Koichi
• Source(s) of Monetary Support: Eli Lilly Japan k.k. / Clinical Research Support Center Kyushu
• Secondary ID(s): UMIN000028309