An Open label Phase 2 Study to Evaluate the Safety and Efficacy of Lenvatinib with Pembrolizumab or Lenvatinib, Pembrolizumab and FLOT in the neoadjuvant / adjuvant treatment for Patients with Gastric Cancer

JRCT ID: jRCT2031210174

Registered date:29/06/2021

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Gastric Cancer
• Date of first enrollment: 22/11/2021
• Target sample size: 43
• Study type: Interventional

Intervention(s)

One cycle is 21 days, with Lenvatinib plus Pembrolizumab repeated 3 cycles before surgery and 3 cycles after surgery, followed by 11 cycles of pembrolizumab monotherapy as the adjuvant treatment.
<FLOT cohort>
One cycle is 21 days, with Lenvatinib, Pembrolizumab plus FLOT repeated 3 cycles before surgery and 3 cycles after surgery, followed by 11 cycles of pembrolizumab monotherapy as the adjuvant treatment.

Outcome(s)

• Primary Outcome: Major pathological response (MPR) rate by central review

Secondary Outcome

MPR rate per investigator assessment
Pathological complete response (pCR) rate per investigator assessment
Tumor response in the gastric primary lesion
Radical resection rate
Treatment completion rate until surgery
Treatment completion rate until adjuvant treatment
Event free survival (EFS)
Overall survival (OS)
The incidence of adverse events

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1)Have gastric and gastroesophageal junction adenocarcinoma
2)Untreated and cT2-4 and/or cN+ without evidence of metastatic disease
3)Patients at least 20 years of age on the day of providing consent.
4)Patients with a performance status of 0 or 1 on the Eastern Cooperative Oncology Group.
5)Patients with adequate organ function at the time of enrollment as defined below:
Neutrophil count >=1,500mm3
Platelet count >= 100,000/mm3
Hemoglobin (Hb) >= 9.0 g/dL,
Total bilirubin =<1.5 mg/dL
AST (GOT) and ALT (GPT) =< 100 IU/L
Creatinine =< 1.5 mg/dL
Urinary protein : It satisfies one of the following (if any of the inspection criteria are satisfied, other examination may not be carried out)
(i) urinary protein (test paper method) is 2+ or less
(ii) Urine Protein Creatinine (UPC) ratio < 3.5
(iii) 24-hour urine protein was measured, urinary protein =< 3,500 mg
International normalized ratio (INR) =< 1.5
6)Patients who not received a blood transfusion within 14 days of registration.
7)Patients have recovered adverse events associated with radiation and surgical operation as pretreatment to Grade 1 or less or baseline or less with CTCAE v5.0 excluding stable symptoms. However, adverse events with stable symptoms even with Grade 2 or higher excluded.
8)Female of childbearing potential who are negative in a pregnancy test within 14 days before enrollment. Both male and female patients should agree to use an adequate method of contraception (total abstinence or use of a male condom plus partner use of contraceptive method [an intrauterine device or hormone releasing system, an contraceptive implant and an oral contraceptive]) starting with the first dose of study therapy through 120 days after the last dose of study therapy. Duration will be determined when the subject is assigned to treatment.
9)Patients capable of taking oral medication.
10)Patients who provided written informed consent to be subjects in this study.

Exclude criteria

1)Patients who have undergone surgical treatment and radiotherapy with in 2 weeks before enrollment.
2)Patients with hypertension that is difficult to control (systolic blood pressure >= 140 mmHg and diastolic blood pressure >= 90 mmHg) despite treatment with several hypotensive agents.
3)Patients with acute coronary syndrome (including myocardial infarction and unstable angina), and with a history of coronary angioplasty or stent placement performed within 6 months before enrollment.
4)Patients with a history of New York Heart Association congestive heart failure of grade II or above, unstable angina, myocardial infarction.
5)Patients have an additional active malignancy (except for definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix) within the past 24 months.
6)Patients have severe (hospitalization required) complications (intenstinal palsy, intestinal obstruction, pulmonary fibrosis, diabetes difficult to control, heart failure, myocardial infarction, unstable angina, renal failure, liver failure, mental disease, cerebrovascular disease etc).
7)Patients with a history of a gastrointestinal perforation and /or gastrointestinal fistula within 6 months before enrollment.
8)Is infected with active hepatitis B (defined as HBs antigen positive) or hepatitis C.
9)Patients with a history of human immunodeficiency virus (HIV).
10)Patients with a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
11)Patients who are administered live vaccines < 30 days before the initiation of treatment with the investigational drug.
12)Patients with concurrent autoimmune disease, or a history of chronic or recurrent autoimmune disease.
13)Patients who require systemic corticosteroids (excluding temporary usage for tests, prophylactic administration for allergic reactions, or to alleviate swelling associated with radiotherapy) or immunosuppressants, or who have received such a therapy < 14 days before enrollment.
14)Patients have serious non-healing wound, ulcer, or bone fracture.
15)Females who are pregnant or breastfeeding.
16)Patients have no intention to comply with the protocol or cannot comply.
17)Patients were judged unsuitable as subject of this study by investigator.

Related Information

• Primary Sponsor: Kawazoe Akihito
• Secondary Sponsor: Shitara Kohei
• Source(s) of Monetary Support: Merck Sharp &amp; Dohme Corp.
• Secondary ID(s): NCT03609359