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

NCT ID: NCT04745988

Last Updated: 2024-11-15

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 43 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-11
• Study Completion Date: 2027-08-31

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.

Detailed Description

This study is an open-label, single-arm, single-center, phase 2 clinical trial. Eligible patients are with previously untreated gastric and gastroesophageal junction adenocarcinoma as defined by cT2-4 and/or cN+ without evidence of metastatic disease. Patients in the exploratory cohort will receive 3 cycles of 20 mg oral Lenvatinib daily plus 200 mg intravenous Pembrolizumab every 3 weeks as the neoadjuvant treatment followed by surgery, and then 3 cycles of Lenvatinib plus Pembrolizumab followed by 11 cycles of Pembrolizumab monotherapy as the adjuvant treatment. Also, Patients in the FLOT cohort will receive 3 cycles of 8 mg oral Lenvatinib daily, 200 mg intravenous Pembrolizumab every 3 weeks and FLOT (Docetaxel 50 mg/m2, Oxaloplatin 85 mg/m2, Levofolinate 200 mg/m2, 5-FU 2600 mg/m2) every 2 weeks as the neoadjuvant treatment followed by surgery, and then 3 cycles of Lenvatinib ,Pembrolizumab plus FLOT followed by 11 cycles of Pembrolizumab monotherapy as the adjuvant treatment.

Conditions

Gastric Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Lenvatinib Plus Pembrolizumab

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.

Group Type: EXPERIMENTAL

Lenvatinib 20mg

Intervention Type: DRUG

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

Pembrolizumab

Intervention Type: 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, Pembrolizumab Plus FLOT

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.

Group Type: EXPERIMENTAL

Pembrolizumab

Intervention Type: 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 8mg

Intervention Type: DRUG

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

Docetaxel

Intervention Type: DRUG

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

Oxaliplatin

Intervention Type: DRUG

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

Levofolinate

Intervention Type: DRUG

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

Fluorouracil

Intervention Type: DRUG

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

Interventions

Lenvatinib 20mg

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

Intervention Type: DRUG

Pembrolizumab

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

Intervention Type: DRUG

Lenvatinib 8mg

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

Intervention Type: DRUG

Docetaxel

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

Intervention Type: DRUG

Oxaliplatin

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

Intervention Type: DRUG

Levofolinate

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

Intervention Type: DRUG

Fluorouracil

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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 ≥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

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, a 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.

Exclusion Criteria

1. Patients who have undergone surgical treatment and radiotherapy within 2 weeks before enrollment.

2. 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.

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 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.

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.

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

National Cancer Center Hospital East

OTHER

Sponsor Role: lead

Responsible Party

Kohei Shitara

Chief of Gastroenterology and Gastrointestinal Oncology Division

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

National Cancer Center Hospital East

Kashiwa, Chiba, Japan

Countries

Japan

Other Identifiers

EPOC2001

Identifier Type: -

Identifier Source: org_study_id