Dataset Information

Phase II study of everolimus for recurrent or progressive pediatric ependymoma.

ABSTRACT:

Background

Preclinical studies have suggested that mTOR pathway signaling may be a potential therapeutic target for childhood ependymoma.

Methods

A phase II clinical trial (ClinicalTrials.gov identifier: NCT02155920) of single-agent everolimus was performed to test the hypothesis that mTOR pathway inhibition would result in tumor responses for children with recurrent and/or progressive ependymomas.

Results

Eleven subjects [sex: 4 females (36.4%); median age: 8 years (range: 2-15 years); race: 9 white; prior therapies: median 6 (range: 3-9)] were enrolled on the study. Ten primary tumors were located in the posterior fossa and one primary tumor was located in the spinal cord. Eight of 9 tumors were PF-A subtype epenydmomas. All subjects were treated with oral everolimus 4.5 mg/m²/day (each cycle = 28 days) that was titrated to achieve serum trough levels of 5-15 ng/ml. Overall, everolimus was well tolerated; except for a single event of grade 3 pneumonia, all adverse events were grade 1-2. No objective tumor responses were observed. Participating subjects experienced tumor progression and discontinued therapy after a median of 2 cycles of therapy (1 cycle = 2; 2 cycles = 6; 3, 4, and 8 cycles = 1 each).

Conclusions

Everolimus does not appear to have activity for children with recurrent or progressive PF-A ependymoma.

SUBMITTER: Bowers DC

PROVIDER: S-EPMC10025810 | biostudies-literature | 2023 Jan-Dec

REPOSITORIES: biostudies-literature

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Publications

Phase II study of everolimus for recurrent or progressive pediatric ependymoma.

Bowers Daniel C DC Rajaram Veena V Karajannis Matthias A MA Gardner Sharon L SL Su Jack Meng-Fen JM Baxter Patricia P Partap Sonia S Klesse Laura J LJ

Neuro-oncology advances 20230101 1

<h4>Background</h4>Preclinical studies have suggested that mTOR pathway signaling may be a potential therapeutic target for childhood ependymoma.<h4>Methods</h4>A phase II clinical trial (ClinicalTrials.gov identifier: NCT02155920) of single-agent everolimus was performed to test the hypothesis that mTOR pathway inhibition would result in tumor responses for children with recurrent and/or progressive ependymomas.<h4>Results</h4>Eleven subjects [sex: 4 females (36.4%); median age: 8 years (range: ...[more]

PMID: 36950217

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Project description:PurposeThe phosphoinositol-3 kinase (PI3K) pathway is frequently dysregulated in endometrial cancer (EC). Hormonal manipulation leads to response in some patients with EC, but resistance derived from PI3K pathway activation has been documented. Targeting mammalian target of rapamycin (mTOR) may overcome endocrine resistance. We conducted a two-institution phase II trial of everolimus and letrozole in women with recurrent EC.Patients and methodsPatients were considered incurable, had measurable disease, and were treated with up to two prior cytotoxic regimens. Everolimus was administered orally at 10 mg daily and letrozole was administered orally at 2.5 mg daily. Each cycle consisted of 4 weeks of therapy. Patients were treated until progression, toxicity, or complete response (CR). The primary end point was the clinical benefit rate (CBR), which was defined as CR, partial response, or stable disease (≥ 16 weeks) by RECIST 1.0 criteria. Translational studies were performed to correlate biomarkers with response.ResultsThirty-eight patients were enrolled (median age, 62 years; range, 24 to 82 years). Thirty-five patients were evaluable for response. The CBR was 40% (14 of 35 patients); the median number of cycles among responders was 15 (range, seven to 29 cycles). The confirmed objective response rate (RR) was 32% (11 of 35 patients; nine CRs and two partial responses; median, 15 cycles; range, eight to 29 cycles). Twenty percent of patients (seven of 35 patients) were taken off treatment after a prolonged CR and at the discretion of the treating clinician. None of the patients discontinued treatment as a result of toxicity. Serous histology was the best predictor of lack of response. Patients with endometrioid histology and CTNNB1 mutations responded well to everolimus and letrozole.ConclusionEverolimus plus letrozole results in a high CBR and RR in patients with recurrent EC. Further development of this combination in recurrent endometrioid EC is under way.

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Dataset Information

Phase II study of everolimus for recurrent or progressive pediatric ependymoma.

Background

Methods

Results

Conclusions

Publications

Phase II study of everolimus for recurrent or progressive pediatric ependymoma.

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