ESPRIT ESP1/SARC025
Research type
Research Study
Full title
ESP1/SARC025 Global Collaboration: A Phase I Study of a Combination of the PARP inhibitor, Niraparib and Temozolomide or Irinotecan in Patients with Previously Treated, incurable Ewing Sarcoma
IRAS ID
146695
Contact name
Sandra Strauss
Contact email
Sponsor organisation
Sarcoma Alliance for Research Through Collaboration (SARC)
Eudract number
2014-005541-50
Clinicaltrials.gov Identifier
Duration of Study in the UK
2 years, 6 months, 0 days
Research summary
Patients with Ewing sarcoma (ES) that is resistant to currently available drugs have a poor prognosis, so it is important to find new and more effective treatments for this disease.
This is a phase I study looking to see whether a new drug niraparib (a polyADP-ribose (PARP) inhibitor) can be safely combined with chemotherapy drugs sometimes used in treatment of ES, temozolomide (TMZ) or Irinotecan. Niraparib, is an unlicensed drug which that works by stopping cancer cells repairing damaged DNA. Temozolomide and Irinotecan work by damaging patient's tumour DNA. There is good evidence from laboratory studies that in ES cells PARP inhibitors potentiate (significantly increase) the effectiveness of temozolomide and Irinotecan.
The primary aim of the study is to find the optimal dose of the combination of nriaparib and temozolomide or irinotecan that can safely be given to patients (the maximum tolerated dose) and assess what side effects occur (dose limiting toxicities). Patients aged 13 years and over with progressive ES after standard treatment will be recruited. Patients will receive up to 12 cycles of niraparib and temozolomide (Arm 1) or niraparib and irinotecan (Arm 2).In Arm 1: patients will be treated on one of three cohorts:
Cohort A, patients will receive niraparib daily and increasing doses of temozolomide
Cohort B, patients will receive interrupted niraparib dosing with constant temozolomide dose
Cohort C, patients will receive interrupted niraparib schedule selected from cohort B and increasing temozolomide doses.
Arm 2:
Patients will receive interrupted doses of niraparib with Irinotecan.The trial is being conducted in 6-10 centres in USA & Europe over 24 months and will recruit 30-50 patients. A number of exploratory studies are being performed to further understand the effects of niraparib and temozolomide or irinotecan in ES and will involve the collection of tumour biopsies and blood samples.
REC name
London - Westminster Research Ethics Committee
REC reference
16/LO/0493
Date of REC Opinion
22 Jul 2016
REC opinion
Further Information Favourable Opinion