Phase I Study of Olaprib and Temozolomide for Ewings Sarcoma

Status: Recruiting
Phase: Phase 1
DFCI Protocol ID: 13-115

This research study is a Phase I clinical trial, which tests the safety of an investigational drug or combination of drugs and also tries to define the appropriate dose of the combination of investigational drugs to use for further studies. "Investigational" means that the combination of drugs is being studied. It also means that the FDA has not yet approved the combination of drugs for your type of cancer. Olaparib works by blocking the activity of a protein called poly (ADP-ribose) polymerase (PARP) which is involved in DNA repair. Cancer cells rely on PARP to repair their DNA and enable them to continue dividing. Olaparib has been used in research studies with other cancers. Information from those other research studies suggests that this drug may help to treat patients with Ewing's sarcoma. The investigational drug olaparib is not approved for any use outside of research studies. Temozolomide (Temodar) is approved by the FDA for the treatment of a type of brain tumor, glioblastoma. It has been studied in Ewing sarcoma in previous research studies. While it is not approved by the FDA for Ewing sarcoma, it is considered part of standard treatment for relapsed disease. Laboratory studies suggest that the combination of olaparib and temozolomide may help kill Ewing sarcoma cells. In this research study, the investigators are looking for the highest dose of the combination of olaparib and temozolomide that can be given safely. The investigators will also begin to collect information about the effects of the combination on Ewing sarcoma.

Conducting Institutions:

Massachusetts General Hospital, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Children's Hospital Boston

Overall PI:

Edwin Choy, MD, Massachusetts General Hospital

Site-responsible Investigators:

George Demetri, MD, Dana-Farber Cancer Institute

Contacts:

Massachusetts General Hospital: Cancer Trials Call Center, 877-789-6100
Dana-Farber Cancer Institute: Emily Leonard, ealeonard@partners.org
Dana-Farber Cancer Institute: Melissa Hohos, mhohos@partners.org
Dana-Farber Cancer Institute: Childrens Hospital Pediatric Clinical Translation Investigation Program CTIP, ctip@partners.org

Eligibility Criteria

Inclusion Criteria:

  -  Histologically confirmed Ewing's sarcoma

  -  Ewing's sarcoma must have progressed following at least one standard prior
     chemotherapy regimen

  -  Life expectancy of at least 16 weeks

  -  Willing to comply with the protocol for the duration of the study including pre- and
     post-treatment biopsies, undergoing treatment, scheduled visits and examinations
     including follow up

  -  Presence of measurable disease

  -  Prior approval from insurance company to obtain oral temozolomide for the duration of
     the study

Exclusion Criteria:

  -  Involvement in the planning and/or conduct of the 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 olaparib and temozolomide

  -  Receiving any systemic chemotherapy, radiotherapy (except for palliative reasons),
     within 2 weeks from the last dose prior to study treatment

  -  Concurrent use of the following classes of inhibitors of CYP3A4: azole antifungals,
     macrolide antibiotics, protease inhibitors

  -  Persistent clinically significant toxicities caused by previous cancer therapy

  -  Previously documented diagnosis of myelodysplastic syndrome (or any dysplastic
     leukocyte morphology suggestive of MDS) 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 disease or active, uncontrolled infection

  -  Unable to swallow orally administered medication and subjects with gastrointestinal
     disorders likely to interfere with absorption of study medication

  -  Pregnant or breastfeeding

  -  Known to be serologically positive for HIV and receiving antiviral therapy

  -  Subjects with known active hepatitis B or C

  -  Known hypersensitivity to olaparib or any of the excipients of the product

  -  Uncontrolled seizures

  -  Need to continue treatment with any prohibited medications or have not completed the
     appropriate washout period for a prohibited medication

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