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

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

1

A 1-year-old girl. The diagnosis was Glioblastoma at our pathology clinic and desmoplastic infantile ganglioglioma at the central pathology clinic. A gene panel test was performed and ROS1 fusion gene was confirmed. The patient had no pre-existing medical conditions, but had received chemotherapy for this brain tumor at another hospital.

One patient was enrolled in the study, and Entrectinib 300 mg/m2 (1 capsule of 100 mg ROZLYTREK capsule) was administered orally once daily after breakfast to this affected child. The total of 13 courses was conducted. A total of 13 courses were conducted, and the drug was stopped on July 6, 2021 at the family's request. The study plan called for a post-observation period to evaluate efficacy after the last day of treatment up to 5 years from the enrollment date or until an event defined as progression-free survival was observed, but the study was terminated at the last observation date upon request from the patients.

The patient developed grade 2 constipation on October 1, 2020. With the use of laxatives, defecation management was good, and spontaneous improvement of constipation was observed after completion of Entrectinib treatment. This is in the category of expected non-serious adverse events and is evaluated as a safety assurance. No other adverse events.

There were no parameters other than imaging evaluation used to determine efficacy, and contrast-enhanced MRI findings of the head and spinal cord were used to evaluate efficacy. The target lesion size visible on contrast-enhanced MRI indicating that this treatment had a good tumor maintenance effect.Only one case was enrolled and no statistical analysis was performed.

In this case, profiling by gene panel testing revealed a mutation in the driver gene, which led to patient-directed therapy for molecular targeted therapy. Although this therapy did not reduce the size of the target lesion, SD was achieved, which is an improvement over the clinical course expected from the original tumor grade. The safety profile was also acceptable, with no unexpected adverse events, no hematologic toxicity during the treatment period, and only grade 2 constipation.

Oct. 01, 2022

No

none

https://jrct.mhlw.go.jp/latest-detail/jRCTs041200030

Kurimoto Michihiro

Nagoya University Hospital

65 Tsurumai-cho, Showa-ku, Nagoya, Aichi

m-kurimoto@med.nagoya-u.ac.jp

Muramatsu Hideki

Nagoya University Hospital

65 Tsurumai-cho, Showa-ku, Nagoya, Aichi

+81-52-744-2294

hideki-muramatsu@med.nagoya-u.ac.jp

Complete

July. 01, 2020

Interventional

randomized controlled trial

open(masking not used)

active control

single assignment

treatment purpose

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.).

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.

Both

Pediatric brain tumor

entrectinib at a dose of 600 mg/m2 orally once per day

Overall best response until four courses

Progression-free survival time, the number of adverse events

+81-52-744-2479

June. 29, 2020

None