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Phase I Study of Olaprib and Temozolomide for Ewings Sarcoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Massachusetts General Hospital
Sponsor:
Information provided by (Responsible Party):
Edwin Choy, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01858168
First received: May 8, 2013
Last updated: March 26, 2014
Last verified: March 2014
  Purpose

This research study is a 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.

Laboratory studies suggest that the combination of olaparib and temozolomide may help kill Ewing sarcoma cells.

In this research study, the investigators are looking for the highest dose of the combination of olaparib and temozolomide that can be given safely. The investigators will also begin to collect information about the effects of the combination on Ewing sarcoma.


Condition Intervention Phase
Ewing Sarcoma
Drug: Olaparib
Drug: Temozolomide
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Olaparib and Temozolomide in Adult Patients With Recurrent/Metastatic Ewing's Sarcoma Following Failure of Prior Chemotherapy

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Determine MTD of olaparib and temozolomide [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Determine the Maximum Tolerated Dose of combine oral administration of olaparib and temozolomide.


Secondary Outcome Measures:
  • Evaluate safety and tolerability of olaparib/temozolomide combination [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Evaluate the safety and tolerability of combination olaparib/temozolomide as defined by CTC version 4.0

  • Objective response in tumor dimensions to olaparib/temozolomide [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 34
Study Start Date: July 2013
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Experimental Treatment Arm
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
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:
  • Temodal
  • SCH52365
  • Temodar

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
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, see Learn About Clinical Studies.

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

Contacts
Contact: Barbara Anderson, RN 617-643-2427 BANDERSON15@PARTNERS.ORG

Locations
United States, Massachusetts
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02215
Contact: Melissa Hohos, RN    617-582-7162    mhohos@partners.org   
Contact: Mark Morley, RN    617-632-3989    mmorley@partners.org   
Principal Investigator: George Demetri, MD         
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Melissa Hohos, RN    617-582-7162    mhohos@partners.org   
Contact: Mark Morley, RN    617-632-3989    mmorley@partners.org   
Principal Investigator: George Demetri, MD         
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Diane Gaucher, RN    617-643-2427    dlgaucher@partners.org   
Contact: Natasha McDowall, BS    617-643-1940    nmcdowall@partners.org   
Principal Investigator: Edwin Choy, MD, PhD         
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Edwin Choy, MD, PhD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Edwin Choy, MD, Prinicipal Investigator, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01858168     History of Changes
Other Study ID Numbers: 13-115
Study First Received: May 8, 2013
Last Updated: March 26, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Sarcoma
Sarcoma, Ewing
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Osteosarcoma
Dacarbazine
Temozolomide
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014