NCCH2107/MK012 trial

JRCT ID: jRCT2031220523

Registered date:20/12/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Epithelioid Sarcoma
• Date of first enrollment: 20/12/2022
• Target sample size: 15
• Study type: Interventional
• Intervention(s): E7438 800 mg BID (1600 mg total daily dose) will be administered orally.

Outcome(s)

• Primary Outcome: Progression free survival rate at 18 weeks (blinded independent central review)
• Secondary Outcome: Progression free survival rate at 18 weeks (investigator's review), progression free survival, overall survival, objective response rate (Blinded independent central review and investigator's review), disease control rate, duration of response, time to response, incidence of adverse effect, serious adverse effect, adverse reaction, and serious adverse reaction

Key inclusion & exclusion criteria

• Age minimum: >= 16age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1) Histopathologically diagnosed as epithelioid sarcoma
2) Metastatic (Stage 4 in AJCC-TNM 8th) or locally advanced disease and not curable by surgery
3) No leptomeningeal metastasis, symptomatic CNS metastasis or spinal metastasis requiring surgical intervention or radiotherapy
4) No malignant pleural effusion, cardiac effusion, or ascites requiring periodic puncture drainage
5) Age at the time of registration is 16 years or older
6) ECOG performance status of 0, 1, or 2
7) Having measurable disease based on RECIST 1.1 for solid tumors by CT within 14 days before registration
8) Having progression of unresectable or metastatic epithelioid sarcoma after at least one regimen of chemotherapy including doxorubicin
9) No prior exposure to tazemetostat or other inhibitor(s) of EZH
10) Not received cytotoxic anti-cancer drug, small molecule drug inhibitor, hormone therapy, and other studies within 21 days before registration
11) Not received monoclonal antibodies within 28 days before registration
12) Not received immune therapy within 42 days before registration
13) Not received operation under general anesthesia within 21 days before registration
14) Not received radiation therapy within 14 days before registration, stereotactic irradiation within 21 days before registration, radiation therapy to 50% of pelvis within 12 weeks before registration
15) Having all laboratory tests performed within 7 days before registration( Allow cardiac US performed within 14days before registration) the values are within the following range. Patients should not receive administration of G-CSF and/or blood transfusion within 14 days before the blood collection
(1) Absolute neutrophil count >= 1,000/mm3
(2) Platelet count >= 10.0 x10(4) /mm3
(3) Hemoglobin >= 9.0 g/dL
(4) Aspartate aminotransferase (AST) <= 100 U/L (allow AST <= 150 U/L in case of liver metastasis)
(5) Alanine aminotransferase (ALT) <= 100 U/L (allow ALT <= 150 U/L in case of liver metastasis)
(6) Total bilirubin <= 1.8 mg/dL
(7) Serum creatinine <= 1.5mg/dL x upper limit of normal (ULN) If serum creatinine >1.2 mg/dL, CCr or eGFR > 51mL/min/1.73m2
(8) APTT < 45 sec.
(9) PT < 15 sec.
(10) QTc corrected by Fridericia's correction <= 480msec
(11) Left ventricular ejection fraction >= 50% by echocardiography
16) Consent to contraception and limited breast-feeding
17) Written informed consent (When registering a minor patient, a signed consent form must be obtained from both the patient and the parent or legal guardian.)

Exclude criteria

1) Active double cancer (except for completely resected basal cell carcinoma, squamous cell carcinoma, carcinoma in situ, intramucosal cancer, superficial bladder cancer, gastrointestinal cancer resected by ESD or EMR, and other cancer free of relapse for more than 2 years).
2) History of T-LBL/T-ALL or myeloid hematologic malignancy
3) Infections requiring systemic treatment
4) Diagnosed as immunodeficiency disease
5) Active gastrointestinal ulceration
6) Current or previous interstitial lung disease or pulmonary fibrosis diagnosed based on imaging or clinical findings
7) Current or previous severe hypersensitive reaction to ingredients including tazemetostat
8) A medical need for the continued use of potent inhibitors of CYP3A, or potent inducer of CYP3A (including St. John's wort). (eligible if 2 weeks or longer have passed since the last use of such agents prior to the first dose of study drugs.)
9) Unable to refrain from grapefruit (including juice) from 1 week prior to study drug administration and throughout the study
10) Patients with any of the following history of cardiovascular impairment
(1) Congestive heart failure of >= New York Heart Association (NYHA) Class II
(2) Uncontrolled arterial hypertension
(3) Unstable angina, myocardial infarction, or stroke within 6 months before registration
(4) Cardiac arrhythmia requiring medical treatment
11) HIV antibody-positive, HBs antigen-positive, or HCV RNA-positive (those who are HCV-RNA-negative are not excluded even if HCV antibody-positive)
12) Though HBs antigen-negative, HBs antibody-positive and/or HBc antibody-positive, and HBV-DNA quantitative test positive (Not excluded if HBV-DNA is below detection sensitivity)
13) Poorly controlled venous thrombus within 14 days before registration
14) Pregnant or breast-feeding women, or women suspected of being pregnant
15) Psychiatric diseases or psychological symptoms interfering with participation in the trial

Related Information

• Primary Sponsor: Yonemori Kan
• Source(s) of Monetary Support: Eisai Co., Ltd.