Phase I Study of Olaparib and Temozolomide for Ewings Sarcoma or Rhabdoomyosarcoma
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ClinicalTrials.gov Identifier: NCT01858168 |
Recruitment Status :
Active, not recruiting
First Posted : May 21, 2013
Last Update Posted : March 12, 2024
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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 or disease | Intervention/treatment | Phase |
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Ewing Sarcoma Rhabdomyosarcoma | Drug: Olaparib Drug: Temozolomide Drug: Irinotecan | Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 93 participants |
Allocation: | Non-Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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 |
Study Start Date : | July 2013 |
Estimated Primary Completion Date : | November 2024 |
Estimated Study Completion Date : | December 2024 |
Arm | Intervention/treatment |
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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
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Drug: Olaparib
Tablets to be taken on an empty stomach twice a day.
Other Name: AZD2281 Drug: Temozolomide Tablets to be taken on an empty stomach before bedtime.
Other Names:
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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
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Drug: Olaparib
Tablets to be taken on an empty stomach twice a day.
Other Name: AZD2281 Drug: Temozolomide Tablets to be taken on an empty stomach before bedtime.
Other Names:
Drug: Irinotecan Administered via IV
Other Name: Camptosar |
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
|
Drug: Olaparib
Tablets to be taken on an empty stomach twice a day.
Other Name: AZD2281 Drug: Temozolomide Tablets to be taken on an empty stomach before bedtime.
Other Names:
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- Determine MTD of olaparib and irinotecan and/or temozolomide [ Time Frame: 30 days ]Determine the Maximum Tolerated Dose of combine oral administration of olaparib and temozolomide.
- Evaluate safety and tolerability of olaparib/irinotecan and/or temozolomide combination [ Time Frame: 2 years ]Evaluate the safety and tolerability of combination olaparib/temozolomide as defined by CTC version 4.0
- Objective response in tumor dimensions to olaparib/irinotecan and/or temozolomide [ Time Frame: 2 years ]Observe objective response in tumor dimensions to olaparib/temozolomide therapy as determined by RECIST 1.1, time of progression free survival (PFS) and overall survival (OS)
- Explore variations in PARP activity and tumor characteristics [ Time Frame: 2 years ]Patients will undergo tumor biopsies before and after starting olaparib and temozolomide therapy. Genomic DNA and RNA will be isolated from these samples and slides will be made to identify specific protein levels. The investigators will assess homologous repair status by measuring gammaH2AX and Rad51 focus formation by immunofluorescence. Biomarkers for apoptosis and DNA repair that the investigators plan to analyze include but are not limited to BRCA1, MRE11A, NBS1, TDG, XPA, Rad50, 53BP1, CHEK2, and MK2.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 16 Years and older (Child, Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01858168
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 |
Principal Investigator: | Edwin Choy, MD, PhD | Massachusetts General Hospital |
Responsible Party: | Edwin Choy, MD, Prinicipal Investigator, Massachusetts General Hospital |
ClinicalTrials.gov Identifier: | NCT01858168 |
Other Study ID Numbers: |
13-115 |
First Posted: | May 21, 2013 Key Record Dates |
Last Update Posted: | March 12, 2024 |
Last Verified: | March 2024 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Sarcoma Rhabdomyosarcoma Sarcoma, Ewing Neoplasms, Connective and Soft Tissue Neoplasms by Histologic Type Neoplasms Myosarcoma Neoplasms, Muscle Tissue Osteosarcoma Neoplasms, Bone Tissue Neoplasms, Connective Tissue |
Irinotecan Temozolomide Olaparib Topoisomerase I Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Antineoplastic Agents, Alkylating Alkylating Agents Poly(ADP-ribose) Polymerase Inhibitors |