CompletedPhase 1

Phase I Study of Olaparib and Temozolomide for Ewings Sarcoma or Rhabdoomyosarcoma

United States49 participantsStarted 2013-07-01

Plain-language summary

This research study is a Three arm 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. Irinotecan is approved by the FDA for the treatment of gastrointestinal cancers. 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 and/or irinotecan may help kill Ewing sarcoma or rhabdomyosarcoma cells. In this research study, the investigators are looking for the highest dose of the combination of olaparib and irinotecan and/or temozolomide that can be given safely. The investigators will also begin to collect information about the effects of the combination on Ewing sarcoma and rhabdomyosarcoma.

Who can participate

Age range16 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

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 diseas…

What they're measuring

Determine MTD of olaparib and irinotecan and/or temozolomide

Timeframe: 30 days

Trial details

NCT IDNCT01858168

SponsorMassachusetts General Hospital

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2024-11-01