ESP1/SARC025 Global Collaboration: A Phase I Study of a Combination of the PARP inhibitor, Niraparib and Temozolomide in Patients with
Previously Treated, incurable Ewing Sarcoma
Co-Principal Investigators:
Sandra Strauss, MD, PhDUniversity College London
Rashmi Chugh, MDUniversity of Michigan
ESP1/SARC025
ESP1/SARC025
Ewing Sarcoma PARPi Consortium (ESP) Collaborating
SARC Sponsor and coordinating center
Tesaro Supporter
Background
Poly(ADP-ribose) (PARP) inhibitors potentiate the activity of cytotoxic agents, particularly DNA damaging agents
Niraparib is a potent and highly selective PARP-1 and -2 inhibitor
Temozolomide (TMZ) is an alkylating agent that is used as a part of multi-agent therapy for ES
Niraparib and TMZ combination treatment causes in vivo tumor regression in patient-derived Ewing Sarcoma xenografts in mice
ESP1/SARC025
ESP1/SARC025
Single arm phase I study Cycle = 28 days Cohort A - enroll patients at the starting
doses of Niraparib (300 mg daily) and TMZ (20, 40, 60, 80, 100 and 120 mg/m2/day, days 2-6)
Anticipated number of patients: 30 - 50
Primary Objective
To define the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of the PARP inhibitor Niraparib and escalating doses of Temozolomide (TMZ) in patients with pre-treated incurable Ewing sarcoma (ES)
Secondary Objectives
To determine the tumor response rate (TRR) of patients with ES treated with Niraparib and TMZ
To determine the progression free survival (PFS), duration of response, 4- and 6-month PFS rate, and overall survival (OS) of patients treated with Niraparib and TMZ
Secondary Objectives
To evaluate pharmacodynamic (PD) markers of response to PARP inhibition in combination with TMZ including measurement of PAR and PARP activity and γH2AX induction
Inclusion Criteria
Age ≥ 13 years Histologically confirmed Ewing sarcoma Recurrent or refractory tumors with no
known curative treatment options ECOG Performance Status 0 – 2 Minimum one prior chemotherapy regimen
received with at least 2 of the following agents: doxorubicin, cyclophosphamide, ifosfamide, and etoposide
Study Status
Contracting In process Anticipated completion by end of 2013
Activation at limited sites in US and UK Late 2013/early 2014
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