NCCH2214 trial (TURTLE trial)

JRCT ID: jRCTs031220736

Registered date:27/03/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Pediatric and AYA malignant solid tumors with no standard therapy or refractory to standard therapy
• Date of first enrollment: 27/03/2023
• Target sample size: 10
• Study type: Interventional
• Intervention(s): Tazemetostat

Outcome(s)

• Primary Outcome: Response rate based on best overall response up to 16 weeks after initiation of treatment in patients with measurable disease
• Secondary Outcome: Progression-free survival, overall survival, disease control rate, adverse event rate

Key inclusion & exclusion criteria

• Age minimum: >= 6month old
• Age maximum: <= 29age old
• Gender: Both

Include criteria

1) Diagnosis of malignant solid tumor by histological or cytological diagnosis; If the histopathological examination was performed prior to enrollment, the timing of the examination is not required. However, if the histopathological examination was performed at another hospital, the pathological specimen must be ordered and the pathological diagnosis must be made again at each study site.
2) One of the following (1) to (3) applies
(1) Tazemetostat is recommended by the expert panel of the gene panel test that has been covered by insurance or conducted as an evaluationtreatment in Japan.
(2) Reduced expression or loss of INI1 or SMARCA 4 by immunostaining.
(3) Diagnosis name is rhabdoid tumor (AT/RT, MRT, RTK), epithelioid sarcoma, synovial sarcoma, chordoma
3) No standard treatment or refractory to standard treatment
4) The patient is not eligible of a corporate clinical trial, investigator-initiated clinical trial, or adva
nced medical treatment being conducted at a medical institution in Japan.
5) The patient does not have symptomatic brainmetastases, cancerous meningitis, or spinal metastases requiring irradiation or surgical procedures.
6) No pericardial, pleural, or ascites effusions requiring treatment.
7) Patients must be between 6 months and 29 years of age at the time of enrollment and have a body surface area of at least 0.17 m2 for patients with CNS tumors and 0.39 m2 for patients without CNS tumors.
8) Karnofsky score (for age 16 years and older) or Lansky score (for age 15 years and younger) of 50 or higher
9) Neoplastic lesions can be confirmed by contrast-enhanced CT or MRI (head, chest, abdomen, pelvis: slice thickness 5 mm or less) within 28 days prior to the date of registration (the same day of the week is acceptable as follows) (regardless of whether measurable lesions are present).
10) Patient has been treated with chemotherapy (treatment in this study is the second or subsequent treatment)
11) Patients with brain tumors have not receivedany new or increased dose of corticosteroids administered intravenously or orally between 7 days prior to and on the day of a contrast-enhanced MRI brain scan performed within 28 days prior to enrollment. If a new or increased dose of corticosteroid medication is administered between the cerebral contrast-enhanced MRI and the start of protocol treatment, a repeat baseline cerebral contrast-enhanced MRI must be performed before the start of protocol treatment.
12) Have not received any anticancer drug (chemotherapy, molecular targeted therapy,immunotherapy, etc.) or other study drug within 28 days prior to the date of enrollment
13) Have not undergone surgery involving general anesthesia within 28 days prior to enrollment
14) Have not received radiotherapy (including Gamma Knife and CyberKnife) within 14 days prior to enrollment
15) Clinical examinations performed within 14 days prior to the date of enrollment meet the following criteria: (1) to (7). However, the patient must not have received granulocyte colony stimulating factor (G-CSF product) administration or blood transfusion within 14 days prior to the date of blood collection
(1) Neutrophil count =>1,000 /mm3
(2) Platelet count =>7.5 x 104/mm3
(3) Hemoglobin =>8.0 g/dL
(4) AST <= 3 times the upper limit of clinical laboratory standards
(5) ALT <= 3 times the upper limit of clinical laboratory standards
(6) Total bilirubin <= 1.5 times the upper limit of clinical laboratory standards
(7) Serum creatinine <= 1.5 times the upper limit of clinical laboratory standards
16) Transcutaneous oxygen saturation (SpO2) =>92% under room air within 14 days prior to enrollment
17) Written consent for participation in the study must be obtained from a surrogate (a person who has parental authority, a guardian, or a similar person who has the best interests of the study subjectin mind); for subjects aged 7 years and older, written consent must be obtained from the study subject him/herself, in principle, in an age-appropriate assent document.
18) For women of childbearing potential, consenthas been obtained for contraception for at least 5weeks after the last administration of the study drug from the time of obtaining consent. For lactating patients, the patient agrees not to breastfeed for at least 3months from the start of study drug administration to at least 3months after the last dose of study drug. Male patients agree to use contraception from the start of study drug administration for at least 3months after the last dose of study drug.

Exclude criteria

1) Patients with active overlapping cancers (the following (1) to (3) are not excluded:
(1) the following cancers that have been completely resected: basal cell carcinoma, stage I spinous cell carcinoma, intraepithelial carcinoma, intramucosal carcinoma, superficial bladder cancer
(2) gastrointestinal cancer curatively resected by ESD or EMR
(3) other cancer that has not recurred for at least 5 years
2) Infectious disease requiring systemic treatment
3) Complicated active gastrointestinal ulcer
4) Complicated or pre-existing interstitial lung dis ease or pulmonary fibrosis diagnosed by imaging or clinical findings
5) Has a history of hypersensitivity reaction to tazemetostat
6) Previous administration of EZH2 inhibitors such as tazemetostat or valemetostat, with a history of ineffectiveness or discontinuation due to adverse events
7) Previous allogeneic hematopoietic stem cell transplantation.
8) Autologous hematopoietic stem cell transplantation within 12 weeks (84 days) prior to enrollment.
9) Has positive HIV antibody, HBs antigen, or HCV antibody (however, patients with positive HCV a ntibody but no detectable HCV RNA are not exclu ded).
10) HBs antigen negative, HBs antibody or HBc a ntibody positive, and HBV-DNA quantification pos itive (patients are not excluded if the sensitivity is l ess than the detection sensitivity).
11) Pregnant or lactating women who need to co ntinue breastfeeding or who may be pregnant afte r the start of study drug administration
12) Patients with psychosis or psychiatric sympto ms that interfere with daily life and make it difficul t for them to participate in the study.
13) History of any of the following (within 6 months prior to enrollment) or complications
(1) Diabetes mellitus judged to be poorly controlled
(2) Chronic congestive heart failure (Class III or hi gher of the New York Heart Association (NYHA) ca rdiac function classification)
(3) History of unstable angina, angioplasty, stent g raft and implantation, or myocardial infarction
(4) Symptomatic or treatable arrhythmia or asympt omatic sustained ventricular tachycardia (except controllable a symptomatic atrial fibrillation)
(14) QT corrected for HR using Fridericia's metho d (QTcF) interval >470 ms on a 12 lead ECG perfo rmed within 14 days prior to enrollment.
(15) Other conditions for which the principal investigator or research assistant investigator consider s the subject to be ineligible.

Related Information

• Primary Sponsor: OGAWA Chitose