Olaparib + Temozolomide for Sarcoma

Recruiting in Palo Alto (17 mi)

+3 other locations

Overseen ByEdwin Choy, MD, PhD

Age: Any Age

Sex: Any

Travel: May be covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: Massachusetts General Hospital

No Placebo Group

Trial Summary

What is the purpose of this trial?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.

Eligibility Criteria

This trial is for individuals with Ewing Sarcoma or Rhabdomyosarcoma who have already undergone at least one standard chemotherapy regimen. Participants must be willing to follow the study protocol, have measurable disease, and a life expectancy of at least 16 weeks. They should not be part of another clinical study within the last 21 days or have received certain treatments recently.

Inclusion Criteria

My cancer can be measured by tests.

My diagnosis is Ewing's sarcoma.

My Ewing's sarcoma has worsened despite having at least one standard chemotherapy.

My insurance has approved temozolomide for the study period.

Exclusion Criteria

I have brain metastases that are causing symptoms and are not under control.

I have not had major surgery in the last 2 weeks.

I have a serious health condition that is not under control.

I am not taking certain fungal, antibiotic, or protease inhibitor medications.

I have been diagnosed with myelodysplastic syndrome or acute myeloid leukemia.

I still have serious side effects from past cancer treatments.

I cannot swallow pills or have a stomach condition that affects medication absorption.

I have active hepatitis B or C.

I am HIV positive and on antiviral treatment.

I have seizures that are not controlled by medication.

Participant Groups

The trial is testing different doses of Olaparib in combination with Temozolomide and/or Irinotecan to find the highest safe dose against Ewing's sarcoma and rhabdomyosarcoma. It's a Phase I study which means it's early in testing these drugs together for safety and appropriate dosage levels.

3Treatment groups

Experimental Treatment

Group I: TwoExperimental Treatment3 Interventions

Olaparib, taken orally twice per day on days 1-7 (week 1) of each cycle Temozolomide, taken orally once per day on days 1-7 (week 1) of each cycle Irinotecan, given by IV once per day on days 1-7 of each cycle

Group II: ThreeExperimental Treatment2 Interventions

Olaparib, taken orally twice per day on days 1-7 (week 1) of each cycle Temozolomide, taken orally once per day on days 1-7 (week 1) of each cycle for patients with Rhabdomyosarcoma

Group III: OneExperimental Treatment2 Interventions

Olaparib, taken orally twice per day on days 1-7 (week 1) of each cycle Temozolomide, taken orally once per day on days 1-7 (week 1) of each cycle for patients with Ewing sarcoma

Irinotecan is already approved in United States, European Union, Japan, Canada for the following indications:

🇺🇸 Approved in United States as Camptosar for: