This research study is a Phase II clinical trial to test the efficacy of Olaparib in adult participants with recurrent/metastatic Ewing's Sarcoma following failure of prior chemotherapy.

Primary Objectives Evaluate the objective response rate of olaparib in adult patients with recurrent and/or metastatic Ewing's sarcoma following failure of conventional chemotherapy.

Secondary Objectives To evaluate the progression-free survival, overall survival, and safety of olaparib in this patient population (ie Number of Participants With Adverse Events). As an exploratory objective, the investigators will evaluate (in subjects who agree to an optional biopsy) differences in pre- and post-treatment tumor DNA alterations and differences in levels of protein and RNA expression related to PARP inhibition.

Study Design Potential subjects who discuss and sign the informed consent form will undergo screening studies. Eligible patients will administer olaparib and obtain restaging imaging studies after 6 and 12 weeks on study, and then every 8 weeks thereafter. Participants will remain on study drug until disease progression, onset of unacceptable toxicities, or subject withdraws consent.

Inclusion Criteria:

• Histologically confirmed Ewing's sarcoma
• Normal organ and bone marrow function
• Life expectancy of at least 16 weeks
• Not pregnant or breastfeeding
• Willing and able to comply with the protocol for the duration of the study
• Presence of measurable disease

Exclusion Criteria:

• Involvement in the planning and/or conduct of ths study
• Previous enrollment in the present study
• Participation in another clinical study with an investigational product during the 21 days prior to first dose of study drug
• Previous exposure to any PARP inhibitor
• Receiving systemic chemotherapy or radiotherapy within 2 weeks of beginning study treatment
• Receiving prohibited classes of inhibitors of CYP3A4
• Persistent clinically significant toxicities caused by previous cancer therapy
• Known myelodysplastic syndrome or acute myeloid leukemia
• Symptomatic, uncontrolled brain metastases
• Major surgery within 14 days of starting study treatment
• Considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disorder or active, uncontrolled infection
• Unable to swallow orally administered medication or with gastrointestinal disorders likely to interfere with absorption of the study medication
• Known to be serologically positive for HIV and receiving antiretroviral therapy
• Known active Hepatitis B or C
• Known hypersensitivity to olaparib or any of the excipients of the product
• Uncontrolled seizures

From initiation of study drug, throughout the study, and for 30 days after the last dose of study drug.