Irinotecan and Temozolomide for Ewing Sarcoma

Inclusion Criteria:

• Histologically confirmed Ewing sarcoma.
• Evidence of Ewing sarcoma translocation by fluorescence in situ hybridization (FISH)or real-time polymerase chain reaction (RT-PCT).
• Recurrent or refractory tumors with no known curative treatment options according tothe judgment of the investigator.
• Prior treatment consisted of standard Ewing Sarcoma chemotherapy agents includingdoxorubicin, vincristine, cyclophosphamide, ifosfamide and etoposide; metastaticrelapsed and unresectable progressive disease (PD);
• Life expectancy of ≥ 3 months.
• Eastern Cooperative Oncology Group performance status 0-1
• Measurable disease on CT or MRI by RECIST 1.1.
• Adequate organ function.
• Time elapsed from previous therapy must be ≥ 3 weeks for systemic therapy, ≥ 2 weeksfor radiation therapy or major surgery.
• Patients who have undergone autologous hematopoietic stem cell transplantation areeligible once they have recovered from all toxicities from therapy.
• Patients who have received allogeneic hematopoietic stem cell transplantation will beeligible 6 months after the procedure provided there is no evidence of activegraft-versus-host disease and immunosuppressive treatment has been discontinued for atleast 30 days.
• Patients with central nervous system disease are eligible for enrollment if they havereceived prior radiotherapy or surgery to sites of central nervous system metastaticdisease, have been off glucocorticoids for at least 4 weeks, have no overt evidence ofneurological deficit and are ≥ 6 weeks from completion of brain irradiation.
• Females of childbearing potential as well as males and their partners must agree touse an effective form of contraception during the study and for 6 months following thelast dose of study medication.

Exclusion Criteria:

• Clinically significant unrelated illness which would, in the judgment of the treatingphysician, compromise the patient's ability to tolerate the investigational agent orbe likely to interfere with the study procedures or results.
• Patients with baseline corrected QT interval(QTc) > 480 msec.
• Known hypersensitivity to any of the components of niraparib or prior hypersensitivityreactions to that class of drugs.
• Known hypersensitivity reaction to temozolomide or any of its components, ordacarbazine (DTIC) or any of its components, and irinotecan or any of its components.
• Concomitant use of any other investigational or anticancer agent(s).
• Pregnant patients or patients who are breast feeding. Subjects capable of pregnancy (post menarche and not post-menopausal, defined as over 12 months since finalmenstrual period) must have a negative pregnancy test within 7 days prior to firstdose.
• Inability to swallow capsules.
• Other clinically significant malignant disease diagnosed within the previous 5 years,excluding intra-epithelial cervical neoplasia or non-melanoma skin cancer.
• Known persistent (> 4 weeks) ≥ Grade 2 neutropenia, ≥ Grade 2 thrombocytopenia or >Grade 3 anemia from prior cancer therapy.
• Other kinds of malignant tumors at the same time.