A feasibility study of patient-proposed healthcare services with entrectinib in patients with ROS1-fusion-positive pediatric brain tumors

JRCT ID: jRCTs041200030

Registered date:10/07/2020

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Pediatric brain tumor
• Date of first enrollment: 03/08/2020
• Target sample size: 1
• Study type: Interventional
• Intervention(s): entrectinib at a dose of 600 mg/m2 orally once per day

Outcome(s)

• Primary Outcome: Overall best response until four courses
• Secondary Outcome: Progression-free survival time, the number of adverse events

Key inclusion & exclusion criteria

• Age minimum: Not applicable
• Age maximum: <= 15age old
• Gender: Both

Include criteria

1.Primary brain tumors with ROS1 gene fusions that are locally advanced; gene fusions are defined as those predicted to translate into a fusion protein with a functional ROS1 kinase domain, without a concomitant second oncodriver (e.g. known, activating mutations in EGFR, KRAS) as determined by a nucleic acid-based diagnostic testing method approved in Japan.
2.Patients who have no satisfactory treatment options for primary CNS tumors.
3.Performance status: PS (ECOG) 0-2 and minimum life expectancy of at least 4 weeks.
4.Age: Male or female from birth to age <=15 years.
5.Patients must have measurable or evaluable disease, as defined in RANO. Measurable disease is defined as bidimensionally contrast enhancing lesions with clearly defined margins by CT or MRI scan, with two perpendicular diameters of at least 10 mm, visible on two or more axial slices that are preferably, at most, 5 mm apart with 0-mm skip.
6.No prior treatment with approved or investigational ROS1 inhibitors.
7.Patients must have recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to enrollment.
8.XRT/External Beam Irradiation: >=14 days after whole brain XRT;>=7 days after stereotactic radiation surgery.
9.Organ function;
i. ANC >= 1,000/microL;
ii. Hemoglobin >= 8.0 g/dL (without transfusion within 14 days of registration)
iii. Platelet count >= 75,000/microL (without transfusion)
iv. Bilirubin <= 1.5 mg/dl
v. ALT <= 3 x upper limit of normal (ULN)
vi. Serum creatinine <= ULN for age (5>=; 0.8mg/dl, 5-10; 1.2mg/dl and 10<=; 1.5mg/dl)
vii. ECG with QTcF <= 480 msec
10. Written informed consent: A signed informed consent and/or assent for study participation will be obtained from patients, parents or caregivers. (Written informed consent should be obtained from patients more than 7 years old.).

Exclude criteria

1.Synchronous or metachronous (within 5 years) malignancies except for carcinoma in situ or mucosal tumors curatively treated with local therapy.
2. Active infection requiring systemic therapy.
3.Body temperature >= 38 degrees Celsius at registration.
4.Women during pregnancy, possible pregnancy or breast-feeding.
5.Continuous systemic use of immunosuppressant including steroid.
6.Uncontrolled diabetes mellitus or routine administration of insulin.
7.Congestive heart failure within 3 months or ejection fraction <= 50%.
8.Inadequately controlled hypertension.
9.Known congenital long QT syndrome.
10.Familial history of long QT syndrome.
11.Positive HBs antigen, positive HBs antibody or positive HBc antibody.
12.Positive HCV antibody.
13.Positive HIV antibody.
14.Pneumonitis, pulmonary fibrosis, or severe lung emphysema on chest CT.
15.Patients who were judged as inappropriate for entry in this study by the principal investigator or sub-investigators.

Related Information

• Primary Sponsor: Kurimoto Michihiro