A phase 1 study of eribulin mesylate (E7389), a novel microtubule‐targeting chemotherapeutic agent, in children with refractory or recurrent solid tumors: A Children's Oncology Group Phase 1 Consortium study (ADVL1314)

Schafer, Eric S.; Rau, Rachel E.; Berg, Stacey L.; Liu, Xiaowei; Minard, Charles G.; D’Adamo, David R.; Scott, Rachael; Reyderman, Larisa; Martinez, Gresel; Devarajan, Sandhya; Reid, Joel M.; Fox, Elizabeth; Weigel, Brenda; Blaney, Susan M.

doi:10.1002/pbc.27066

Cited by 16 publications

(15 citation statements)

References 34 publications

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“…Although we were unable to identify the reason for the lack of response in our patient population, the PPTP investigators are currently evaluating whether the drug exposures in the preclinical models accurately reflect the actual drug exposure in patients. Additionally, we note that although the PPTP data did not correlate with clinical response in our patient population, there are preliminary data to suggest that eribulin may have clinical activity in patients with Ewing sarcoma . Additionally, the PPTP has demonstrated preclinical activity of the MEK inhibitor selumetinib in the treatment of astrocytoma, which has correlated thus far with clinical activity as demonstrated in a phase I clinical trial of low‐grade astrocytoma .…”

Section: Discussionmentioning

confidence: 64%

“…Additionally, we note that although the PPTP data did not correlate with clinical response in our patient population, there are preliminary data to suggest that eribulin may have clinical activity in patients with Ewing sarcoma. 23 Additionally, the PPTP has demonstrated preclinical activity of the MEK inhibitor selumetinib in the treatment of astrocytoma, 24 which has correlated thus far with clinical activity as demonstrated in a phase I clinical trial of low-grade astrocytoma. 25 In addition, evaluations are being conducted to consider whether resistant/recurrent preclinical models may demonstrate less tumor activity compared with what was studied in our patient population.…”

Section: Discussionmentioning

confidence: 97%

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A phase II study of eribulin in recurrent or refractory osteosarcoma: A report from the Children's Oncology Group

Isakoff

Goldsby

Villaluna

et al. 2018

Pediatric Blood & Cancer

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Background Patients with recurrent or refractory osteosarcoma have a poor prognosis with less than 30% surviving two years. Eribulin is a synthetic analog of halichondrin B, has a novel mechanism of action when compared with other microtubule inhibitors, and may have antitumor activity in osteosarcoma. Methods A prospective study was designed to assess the disease control success at four months and objective response rates in patients with recurrent or refractory osteosarcoma treated with eribulin. Eligible patients were between 12 and 50 years of age, had measurable tumor, and met standard organ function requirements. Patients were given eribulin 1.4 mg/m2/dose on days 1 and 8 of each 3‐week cycle for up to 24 months if there was no progressive disease. Response to therapy was assessed using RECIST 1.1 criteria after cycles 2 and 5 and every fourth cycle thereafter. Results Nineteen patients enrolled on the AOST1322 study. The median age of enrollment was 16 years (range, 12–25 years). Twelve patients were male and seven female. Eribulin was well tolerated, with neutropenia identified as the most common toxicity. The median progression‐free survival was 38 days and no patients reached the four‐month time point without progression. No objective responses were seen in any patient. Conclusion This study rapidly assessed the clinical activity of a novel agent in this patient population. Eribulin was well tolerated, but there were no patients who demonstrated objective response, and all patients had progression prior to four months.

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 97%

A phase II study of eribulin in recurrent or refractory osteosarcoma: A report from the Children's Oncology Group

Isakoff

Goldsby

Villaluna

et al. 2018

Pediatric Blood & Cancer

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“…In sarcoma treatment, eribulin is FDA-approved for adult patients with liposarcoma who previously received an anthracycline 38 . The COG performed a phase 1 trial of eribulin in children with advanced solid tumors; one of the evaluable patients with ES experienced a partial response for four cycles 39 . An ongoing phase 2 trial (ClinicalTrials.gov Identifier: NCT03441360) is assessing eribulin in patients with relapsed ES 40 .…”

Section: Eribulinmentioning

confidence: 99%

Emerging novel agents for patients with advanced Ewing sarcoma: a report from the Children’s Oncology Group (COG) New Agents for Ewing Sarcoma Task Force

et al. 2019

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Ewing sarcoma is a small round blue cell malignancy arising from bone or soft tissue and most commonly affects adolescents and young adults. Metastatic and relapsed Ewing sarcoma have poor outcomes and recurrences remain common. Owing to the poor outcomes associated with advanced disease and the need for a clear research strategy, the Children’s Oncology Group Bone Tumor Committee formed the New Agents for Ewing Sarcoma Task Force to bring together experts in the field to evaluate and prioritize new agents for incorporation into clinical trials. This group’s mission was to evaluate scientific and clinical challenges in moving new agents forward and to recommend agents and trial designs to the Bone Tumor Committee. The task force generated a framework for vetting prospective agents that included critical evaluation of each drug by using both clinical and non-clinical parameters. Representative appraisal of agents of highest priority, including eribulin, dinutuximab, cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, anti-angiogenic tyrosine kinase inhibitors, and poly-ADP-ribose polymerase (PARP) inhibitors, is described. The task force continues to analyze new compounds by using the paradigm established.

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“…The microtubule inhibitor eribulin has received regulatory approval for adult soft tissue sarcoma and has shown preclinical activity against mouse models of Ewing sarcoma,39 as well as a response in the recently completed pediatric Phase I trial 40. Ewing sarcoma is one of the target tumors included in an ongoing single-agent Phase II trial of eribulin [NCT03441360], as well as in combination with irinotecan [NCT03245450].…”

Section: Introductionmentioning

confidence: 99%

<p>Management of recurrent Ewing sarcoma: challenges and approaches</p>

Mater¹,

Wagner²

2019

OTT

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Although many patients with newly diagnosed Ewing sarcoma can become long-term survivors, relapse remains an important clinical problem for which there is no standard approach. Several prognostic factors have been identified, and these may help guide patient counseling and therapy decisions. A variety of chemotherapy regimens have produced responses in patients with recurrent Ewing sarcoma, but no comparative studies have been completed to show superiority of any one particular approach. In addition, the optimum length of therapy for salvage regimens and use of local control measures remains unknown. The likelihood of cure remains low and the gaps in our knowledge are great, and so enrollment on clinical trials should be strongly encouraged for these patients when feasible. Because Ewing sarcoma is relatively rare, some pediatric and adult oncologists may be less familiar with the management of relapsed patients. In this review, we address common questions facing the clinician and patient, and provide an update on new strategies for therapy.

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A phase 1 study of eribulin mesylate (E7389), a novel microtubule‐targeting chemotherapeutic agent, in children with refractory or recurrent solid tumors: A Children's Oncology Group Phase 1 Consortium study (ADVL1314)

Abstract: Eribulin was well tolerated in children with refractory or recurrent solid tumors with neutropenia identified as the primary DLT. The RP2D of eribulin is 1.4 mg/m /dose on days 1 and 8 of a 21-day cycle.

Cited by 16 publications

References 34 publications

A phase II study of eribulin in recurrent or refractory osteosarcoma: A report from the Children's Oncology Group

A phase II study of eribulin in recurrent or refractory osteosarcoma: A report from the Children's Oncology Group

Emerging novel agents for patients with advanced Ewing sarcoma: a report from the Children’s Oncology Group (COG) New Agents for Ewing Sarcoma Task Force

<p>Management of recurrent Ewing sarcoma: challenges and approaches</p>

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