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Phase I Study of Olaparib and Temozolomide in Adult Patients With Recurrent/Metastatic Ewing's Sarcoma Following Failure of Prior Chemotherapy

Phase 1
18 Years
Not Enrolling
Ewing Sarcoma

Thank you

Trial Information

Phase I Study of Olaparib and Temozolomide in Adult Patients With Recurrent/Metastatic Ewing's Sarcoma Following Failure of Prior Chemotherapy

If the patient agrees to participate in this research study they will be asked to undergo
some screening tests and procedures to confirm that they are eligible. Many of these tests
and procedures are likely to be part of regular cancer care and may be done even if it turns
out that they do not take part in the research study. If they have had some of these tests
and procedures recently, they may or may not have to be repeated. These tests and procedures
will include: a medical history, complete physical examination, performance status, tumor
assessment, EKG, blood tests, pregnancy test, confirmation of pathology report and obtain
insurance approval to receive temozolomide. If these tests show that the patient is eligible
to participate in the research study, they will begin the study drug administration. If they
do not meet the eligibility criteria, they will not be able to participate in this research

Biomarkers are substances such as genes and proteins that are important biological
"indicators" that can be measured in tumor tissue. The investigators would like to look at
biomarkers before and after patients receive study drug administration. Comparing the
biomarkers from tissue collected before and after receiving study treatments may help us
find biomarkers that are associated with response to study treatment or lack of response to
study drug administration.

Before the patient starts study drug administration, if the investigators determine that the
patient is healthy enough for a biopsy, the patient will undergo a biopsy to provide tumor
tissue for the research tests described above. (If it is determined that the patient should
not have a biopsy, they can still take part in this research study).

The investigators are looking for the highest doses of olaparib and temozolomide that can be
administered safely without severe or unmanageable side effects to participants that have
Ewing's sarcoma. Therefore, not everyone who participates in this research study will
receive the same doses of olaparib and temozolomide. The doses the patients get will depend
on the number of participants who have been enrolled in the study before them and how well
they have tolerated their doses. The investigators will tell patients how the dose level you
receive compares to doses given previously in this study.

Olaparib and temozolomide will ge given in cycles of 21 days (3 weeks). Both olaparib and
temozolomide are drugs that are taken by mouth. Patients will take olaparib and temozolomide
on days 1-7 (week 1) of each cycle. Patients will take olaparib twice per day and
temozolomide once per day.

The investigators will give patients a drug diary to record the doses of olaparib and
temozolomide that they take each day. The diary will also include special instructions for
taking olaparib and temozolomide. A member of the study team will show patients how to enter
their doses in the diary.

During cycle 1 patients will come to the clinic on Days 1 and 8 (weeks 1 and 2). During
cycles 2-6 they will come to the clinic on Day 1 of each cycle. During cycles 8 and beyond
they will come to the clinic every 9 weeks.

At each study visit patients will undergo the following procedures: a physical exam,
questions about their health (problems, medications, side effects), performance status and
blood tests. Additionally, during the visit on Cycle 1, Day 8 patients will have an EKG. 4-6
weeks after starting study drug administration their blood will be tested for its clotting
ability on Day 1 of Cycle 2. They will also undergo a biopsy to provide tumor tissue for
biomarker research tests. Every 9 weeks they wil have a CT scan or MRI to measure your

Patients will be asked to return to the clinic about 30 days after stopping study drug. At
this visit the following will be done: physical exam, questions about their health,
performance status and blood tests. Patients will be asked to return study drug bottles and
any unused study drug at this visit.

The investigators would like to keep track of the patients' medical condition for as long as
they allow. The investigators would like to do this by either calling patients on the
telephone or following them at clinic visits every 3 months. Keeping in touch with patients
and checking their condition helps the investigators look at the long-term effects of the
research study.

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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Determine MTD of olaparib and temozolomide

Outcome Description:

Determine the Maximum Tolerated Dose of combine oral administration of olaparib and temozolomide.

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Edwin Choy, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Massachusetts General Hospital


United States: Food and Drug Administration

Study ID:




Start Date:

May 2013

Completion Date:

July 2017

Related Keywords:

  • Ewing Sarcoma
  • Sarcoma, Ewing's
  • Neuroectodermal Tumors, Primitive, Peripheral
  • Sarcoma



Dana-Farber Cancer Institute Boston, Massachusetts  02115
Brigham and Women's Hospital Boston, Massachusetts  02115
Massachusetts General Hospital Boston, Massachusetts  02114-2617