Clinical Trial - NCT01858168

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

Recruiting

Sponsor: Massachusetts General Hospital

Collaborators:

Information provided by (Responsible party): Principal Investigator Massachusetts General Hospital Edwin Choy, MD Prinicipal Investigator

ClinicalTrials.gov Identifier: NCT01858168

Protocol Info

Short Description: Phase I: Temodar and Olaparib in Sarcoma
Long Description: Phase I Study of Olaparib with Irinotecan and/or Temozolomide in Adolescent and Adult Patients with Recurrent/Metastatic Ewing Sarcoma or Rhabdomyosarcoma following failure of prior chemotherapy
MGH Status: Open
Sponsor: Investigator
Disease Program: Sarcoma

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.




Purpose

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.
Condition Title Intervention Phase
Ewing Sarcoma Rhabdomyosarcoma Olaparib Temozolomide Irinotecan Phase 1
Study Type Interventional
Official Title Phase I Study of Olaparib and Temozolomide in Adult Patients With Recurrent/Metastatic Ewing's Sarcoma or Rhabdomyosarcoma Following Failure of Prior Chemotherapy

Primary Outcome Measures

Determine MTD of olaparib and irinotecan and/or temozolomide [Time Frame: 30 days] [Designated as safety issue: ]


Secondary Outcome Measures

Evaluate safety and tolerability of olaparib/irinotecan and/or temozolomide combination [Time Frame: 2 years] [Designated as safety issue: ]

Objective response in tumor dimensions to olaparib/irinotecan and/or temozolomide [Time Frame: 2 years] [Designated as safety issue: ]

Explore variations in PARP activity and tumor characteristics [Time Frame: 2 years] [Designated as safety issue: ]

Estimated Enrollment: 93
Study Start Date: July 2013
Estimated Study Completion Date: July 2024
Estimated Primary Completion Date: July 2022
Arms Assigned Interventions

Experimental:One

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
Drug:Temozolomide
Tablets to be taken on an empty stomach before bedtime.

Experimental:Two

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
Drug:Irinotecan
Administered via IV

Experimental:Three

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

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01858168

Locations

  • United States, Massachusetts
    • Massachusetts General Hospital Boston, Massachusetts, United States, 02114
    • Boston Children's Hospital Boston, Massachusetts, United States, 02115
    • Brigham and Women's Hospital Boston, Massachusetts, United States, 02215
    • Dana-Farber Cancer Institute Boston, Massachusetts, United States, 02215
  • United States, Tennessee
    • St. Jude's Children's Research Hospital Memphis, Tennessee, United States, 38105

Sponsors and Collaborators

Massachusetts General Hospital

More Information

No publications provided

Responsible Party: Principal Investigator Massachusetts General Hospital Edwin Choy, MD Prinicipal Investigator
ClinicalTrials.gov Identifier: NCT01858168
Other Study ID Numbers:
Study First Received:
Last Updated:
Health Authority:

Additional relevant MeSH terms:

Sarcoma

Rhabdomyosarcoma

Sarcoma, Ewing

Irinotecan

Temozolomide

Olaparib

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on October 14, 2021