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

NCT04745988 | Active Not Recruiting Phase 2

• 1 other identifier: EPOC2001
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

This study is 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.

Conditions

Gastric Cancer

Outcome Measures

Primary Outcomes (1)

• Major pathological response (MPR) rate

  The MPR rate will be defined as the proportion of patients whose percentage of residual tumor in the stomach and lymph node decreased to \< 10%, as determined by a pathologist.

  6 months

Secondary Outcomes (8)

• Pathological complete response (pCR) rate

  6 months

• Tumor response in the gastric primary lesion

  6 months

• Radical resection rate

  6 months

• Treatment completion rate until surgery

  6 months

• Treatment completion rate until adjuvant treatment

  1 year 8 months

Study Arms (2)

Lenvatinib Plus Pembrolizumab

EXPERIMENTAL

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.

Drug: Lenvatinib 20mg; Drug: Pembrolizumab

Lenvatinib, Pembrolizumab Plus FLOT

EXPERIMENTAL

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.

Drug: Pembrolizumab; Drug: Lenvatinib 8mg; Drug: Docetaxel; Drug: Oxaliplatin; Drug: Levofolinate; Drug: Fluorouracil

Interventions

Lenvatinib 20mg DRUG

Lenvatinib will be administered at a dose of 20mg as oral dose, once a day.

Lenvatinib Plus Pembrolizumab

Pembrolizumab DRUG

Pembrolizumab will be administered at a dose of 200mg as a 30-minutes IV infusion, Q3W (25 minutes to 40 minutes are acceptable).

Lenvatinib Plus Pembrolizumab; Lenvatinib, Pembrolizumab Plus FLOT

Lenvatinib 8mg DRUG

Lenvatinib will be administered at a dose of 8mg as oral dose, once a day.

Lenvatinib, Pembrolizumab Plus FLOT

Docetaxel DRUG

Docetaxel will be administered at a dose of 50mg/m\^2 as a IV infusion, Q2W.

Lenvatinib, Pembrolizumab Plus FLOT

Oxaliplatin DRUG

Oxaliplatin will be administered at a dose of 85mg/m\^2 as a IV infusion, Q2W.

Lenvatinib, Pembrolizumab Plus FLOT

Levofolinate DRUG

Levofolinate will be administered at a dose of 200mg/m\^2 as a IV infusion, Q2W.

Lenvatinib, Pembrolizumab Plus FLOT

Fluorouracil DRUG

Levofolinate will be administered at a dose of 2600mg/m\^2 as a IV infusion, Q2W.

Lenvatinib, Pembrolizumab Plus FLOT

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have gastric and gastroesophageal junction adenocarcinoma
• Untreated and cT2-4 and/or cN+ without evidence of metastatic disease
• Patients at least 20 years of age on the day of providing consent.
• Patients with a performance status of 0 or 1 on the Eastern Cooperative Oncology Group.
• Patients with adequate organ function at the time of enrollment as defined below:
• Neutrophil count ≥1500mm3
• Platelet count ≥10 × 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 ≦ 3500 mg
• International normalized ratio (INR) ≤ 1.5
• Patients who not received a blood transfusion within 14 days of registration.
• 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.

You may not qualify if:

• Patients who have undergone surgical treatment and radiotherapy within 2 weeks before enrollment.
• Patients with hypertension that is difficult to control (systolic blood pressure ≥160 mmHg and diastolic blood pressure ≥90 mmHg) despite treatment with several hypotensive agents.
• 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.
• Patients with a history of New York Heart Association congestive heart failure of grade II or above, unstable angina, myocardial infarction.
• Patients have an addigional 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.
• 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).
• Patients with a history of a gastrointestinal perforation and /or gastrointestinal fistula within 6 months before enrollment.
• Is infected with active hepatitis B (defined as HBs antigen positive) or hepatitis C.
• Patients with a history of human immunodeficiency virus (HIV).
• Patients with a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Patients who are administered live vaccines \<30 days before the initiation of treatment with the investigational drug.
• Patients with concurrent autoimmune disease, or a history of chronic or recurrent autoimmune disease.
• 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.
• Patients have serious non-healing wound, ulcer, or bone fracture.
• Females who are pregnant or breastfeeding.

Sponsors & Collaborators

• National Cancer Center Hospital East: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

National Cancer Center Hospital East

Kashiwa, Chiba, Japan

Location

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

lenvatinib; pembrolizumab; Docetaxel; Oxaliplatin; Leucovorin; Fluorouracil

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of Gastroenterology and Gastrointestinal Oncology Division

Study Record Dates

• First Submitted: February 8, 2021
• First Posted: February 9, 2021
• Study Start: November 11, 2021
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2027
• Last Updated: April 9, 2026

Record last verified: 2026-04

Locations

JP (1)