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An Open Label Phase 2 Study to Evaluate the Safety and Efficacy of Lenvatinib With Pembrolizumab in the Neoadjuvant / Adjuvant Treatment for Patients With Gastric Cancer

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ClinicalTrials.gov Identifier: NCT04745988
Recruitment Status : Recruiting
First Posted : February 9, 2021
Last Update Posted : November 26, 2021
Sponsor:
Collaborator:
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
Kohei Shitara, National Cancer Center Hospital East

Brief Summary:
This study is an open label phase 2 study to evaluate the safety and efficacy of Lenvatinib with Pembrolizumab in the neoadjuvant / adjuvant treatment for Patients with Gastric Cancer.

Condition or disease Intervention/treatment Phase
Gastric Cancer Drug: Lenvatinib Drug: Pembrolizumab Phase 2

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 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open Label Phase 2 Study to Evaluate the Safety and Efficacy of Lenvatinib With Pembrolizumab in the Neoadjuvant / Adjuvant Treatment for Patients With Gastric Cancer
Actual Study Start Date : November 11, 2021
Estimated Primary Completion Date : August 2025
Estimated Study Completion Date : August 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Stomach Cancer

Arm Intervention/treatment
Experimental: 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.
Drug: Lenvatinib
Lenvatinib will be administered at a dose of 20mg as oral dose, once a day.

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).




Primary Outcome Measures :
  1. Major pathological response (MPR) rate [ Time Frame: 6 months ]
    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.


Secondary Outcome Measures :
  1. Pathological complete response (pCR) rate [ Time Frame: 6 months ]
    The pCR rate will be defined as the proportion of patients whose tumor in the stomach and lymph node completely disappeared, as determined by a pathologist.

  2. Tumor response in the gastric primary lesion [ Time Frame: 6 months ]
    The number of patients achieving endoscopic CR, PR, SD, or PD will be separately tabulated.

  3. Radical resection rate [ Time Frame: 6 months ]
    The radical resection rate will be defined as the proportion of patients who underwent a radical resection (R0 resection).

  4. Treatment completion rate until surgery [ Time Frame: 6 months ]
    The treatment completion rate will be defined as the proportion of patients who started the protocol treatment, completed a three-cycle treatment with the study drug, and then underwent a radical resection (R0 resection).

  5. Treatment completion rate until adjuvant treatment [ Time Frame: 1 year 8 months ]
    The treatment completion rate will be defined as the proportion of patients who started the protocol treatment, completed a three-cycle treatment with the study drug, and then underwent a radical resection (R0 resection) and adjuvant treatment was performed up to 14 cycles.

  6. Event free survival (EFS) [ Time Frame: 3 years ]

    The registration date is the starting date, and is defined as the period until the event that occurs any of the following.

    • Disease progression based on image evaluation using RECIST 1.1
    • Recurrence based on CT or biopsy among patients with no postoperative lesions
    • Death of any cause If it is determined to be exacerbated based on the image evaluation, the inspection date on which the image inspection was performed shall be the exacerbation date.

    Secondary primary malignancies are not an EFS event. Patients for whom no EFS event has been recorded will be censored on the final image evaluation date.


  7. Overall survival (OS) [ Time Frame: 3 years ]

    The period will be from the day of enrollment, as the starting date of the computation, to the day of death of any cause.

    Surviving patients should be censored on the last day of PFS confirmed (Confirmation of survival by telephone inquiry will be acceptable. However, the fact of confirming survival should be documented in medical records.).

    Patients who are lost to follow up should be censored on the last day when their survival is confirmed before being lost to follow up.


  8. The incidence of adverse events [ Time Frame: Up to 30 days after the last dose ]
    For adverse events due to protocol treatment, determine the frequency of worst grades in all courses according to CTCAE v5.0, the incidence of adverse events of Grade 3 or higher, and the incidence of adverse events of Grade 4 or higher.



Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04745988


Contacts
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Contact: Akihito Kawazoe, MD +81-4-7133-1111 LenvaPem_core@east.ncc.go.jp

Locations
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Japan
National Cancer Center Hospital East Recruiting
Kashiwa, Chiba, Japan
Contact: Akihito Kawazoe, MD    +81-4-7133-1111    LenvaPem_core@east.ncc.go.jp   
Principal Investigator: Akihito Kawazoe, MD         
Sponsors and Collaborators
National Cancer Center Hospital East
Merck Sharp & Dohme LLC
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Responsible Party: Kohei Shitara, Chief of Gastroenterology and Gastrointestinal Oncology Division, National Cancer Center Hospital East
ClinicalTrials.gov Identifier: NCT04745988    
Other Study ID Numbers: EPOC2001
First Posted: February 9, 2021    Key Record Dates
Last Update Posted: November 26, 2021
Last Verified: November 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Pembrolizumab
Lenvatinib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action