Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT01858168 |
| Other study ID # |
13-115 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
Phase 1
|
| First received |
|
| Last updated |
|
| Start date |
July 2013 |
| Est. completion date |
December 2024 |
Study information
| Verified date |
March 2024 |
| Source |
Massachusetts General Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
Description:
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
study.
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 irinotecan and/or
temozolomide that can be administered safely without severe or unmanageable side effects to
participants that have Ewing's sarcoma or rhabdomyosarcoma. Therefore, not everyone who
participates in this research study will receive the same doses of olaparib, irinotecan,
and/or 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 irinotecan and/or 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. Irinotecan is given by IV, once per day,
on days 1-7 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 tumor.
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.
