Olaparib in Adults With Recurrent/Metastatic Ewing's Sarcoma
Primary Purpose
Ewing's Sarcoma
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Olaparib
Sponsored by
About this trial
This is an interventional treatment trial for Ewing's Sarcoma focused on measuring Recurrent, Metastatic
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed Ewing's sarcoma
- Normal organ and bone marrow function
- Life expectancy of at least 16 weeks
- Not pregnant or breastfeeding
- Willing and able to comply with the protocol for the duration of the study
- Presence of measurable disease
Exclusion Criteria:
- Involvement in the planning and/or conduct of ths 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 study drug
- Previous exposure to any PARP inhibitor
- Receiving systemic chemotherapy or radiotherapy within 2 weeks of beginning study treatment
- Receiving prohibited classes of inhibitors of CYP3A4
- Persistent clinically significant toxicities caused by previous cancer therapy
- Known myelodysplastic syndrome 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 disorder or active, uncontrolled infection
- Unable to swallow orally administered medication or with gastrointestinal disorders likely to interfere with absorption of the study medication
- Known to be serologically positive for HIV and receiving antiretroviral therapy
- Known active Hepatitis B or C
- Known hypersensitivity to olaparib or any of the excipients of the product
- Uncontrolled seizures
Sites / Locations
- Massachusetts General Hospital
- Brigham and Women's Hospital
- Dana-Farber Cancer Institute
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Olaparib
Arm Description
400mg PO BID Continuous
Outcomes
Primary Outcome Measures
Objective Response Rate of Olaparib
Number of participants with objective response rate as defined as PR+CR as determined by RECIST vs. 1.1.
Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Secondary Outcome Measures
Progression-Free Survival
Number of patients with progression free survival after two years from starting the trial.
Overall Survival
Number of patients survived for 2 years after enrolling onto this study.
Number of Participants Experiencing a Grade 3 or 4 Clinically Significant and Related Adverse Event
Adverse events were graded according to CTCAE v.4 (Common Terminology Criteria for Adverse Events). Events are graded on a scale of 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal. Only events that are clinically significant and which the treating investigator considers to be related to administration of olaparib are counted for this outcome measure.
Full Information
NCT ID
NCT01583543
First Posted
April 18, 2012
Last Updated
April 11, 2017
Sponsor
Massachusetts General Hospital
1. Study Identification
Unique Protocol Identification Number
NCT01583543
Brief Title
Olaparib in Adults With Recurrent/Metastatic Ewing's Sarcoma
Official Title
Phase II Study of the PARP Inhibitor, Olaparib, in Adult Patients With Recurrent/Metastatic Ewing's Sarcoma Following Failure of Prior Chemotherapy
Study Type
Interventional
2. Study Status
Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
May 2012 (undefined)
Primary Completion Date
January 2014 (Actual)
Study Completion Date
November 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This research study is a Phase II clinical trial to test the efficacy of Olaparib in adult participants with recurrent/metastatic Ewing's Sarcoma following failure of prior chemotherapy.
Detailed Description
Primary Objectives Evaluate the objective response rate of olaparib in adult patients with recurrent and/or metastatic Ewing's sarcoma following failure of conventional chemotherapy.
Secondary Objectives To evaluate the progression-free survival, overall survival, and safety of olaparib in this patient population (ie Number of Participants With Adverse Events). As an exploratory objective, the investigators will evaluate (in subjects who agree to an optional biopsy) differences in pre- and post-treatment tumor DNA alterations and differences in levels of protein and RNA expression related to PARP inhibition.
Study Design Potential subjects who discuss and sign the informed consent form will undergo screening studies. Eligible patients will administer olaparib and obtain restaging imaging studies after 6 and 12 weeks on study, and then every 8 weeks thereafter. Participants will remain on study drug until disease progression, onset of unacceptable toxicities, or subject withdraws consent.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ewing's Sarcoma
Keywords
Recurrent, Metastatic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Olaparib
Arm Type
Experimental
Arm Description
400mg PO BID Continuous
Intervention Type
Drug
Intervention Name(s)
Olaparib
Other Intervention Name(s)
AZD 2281
Intervention Description
400mg PO BID Continuous
Primary Outcome Measure Information:
Title
Objective Response Rate of Olaparib
Description
Number of participants with objective response rate as defined as PR+CR as determined by RECIST vs. 1.1.
Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Progression-Free Survival
Description
Number of patients with progression free survival after two years from starting the trial.
Time Frame
Two years
Title
Overall Survival
Description
Number of patients survived for 2 years after enrolling onto this study.
Time Frame
Two years
Title
Number of Participants Experiencing a Grade 3 or 4 Clinically Significant and Related Adverse Event
Description
Adverse events were graded according to CTCAE v.4 (Common Terminology Criteria for Adverse Events). Events are graded on a scale of 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal. Only events that are clinically significant and which the treating investigator considers to be related to administration of olaparib are counted for this outcome measure.
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically confirmed Ewing's sarcoma
Normal organ and bone marrow function
Life expectancy of at least 16 weeks
Not pregnant or breastfeeding
Willing and able to comply with the protocol for the duration of the study
Presence of measurable disease
Exclusion Criteria:
Involvement in the planning and/or conduct of ths 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 study drug
Previous exposure to any PARP inhibitor
Receiving systemic chemotherapy or radiotherapy within 2 weeks of beginning study treatment
Receiving prohibited classes of inhibitors of CYP3A4
Persistent clinically significant toxicities caused by previous cancer therapy
Known myelodysplastic syndrome 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 disorder or active, uncontrolled infection
Unable to swallow orally administered medication or with gastrointestinal disorders likely to interfere with absorption of the study medication
Known to be serologically positive for HIV and receiving antiretroviral therapy
Known active Hepatitis B or C
Known hypersensitivity to olaparib or any of the excipients of the product
Uncontrolled seizures
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Edwin Choy, MD PhD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
25374341
Citation
Choy E, Butrynski JE, Harmon DC, Morgan JA, George S, Wagner AJ, D'Adamo D, Cote GM, Flamand Y, Benes CH, Haber DA, Baselga JM, Demetri GD. Phase II study of olaparib in patients with refractory Ewing sarcoma following failure of standard chemotherapy. BMC Cancer. 2014 Nov 5;14:813. doi: 10.1186/1471-2407-14-813.
Results Reference
result
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Olaparib in Adults With Recurrent/Metastatic Ewing's Sarcoma
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