Olaparib in Adults With Recurrent/Metastatic Ewing's Sarcoma

Phase 2

Completed

• Conditions: Ewing's Sarcoma
• Interventions: Drug: Olaparib

• Registration Number: NCT01583543
• Lead Sponsor: Massachusetts General Hospital

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.

Study Timeline

• Study First Submitted: 2012-04-18
• Study First Submitted QC: 2012-04-23
• Study First Posted: 2012-04-24
• Study Start: 2012-05
• Primary Completion: 2014-01
• Study Completion: 2014-11
• Results First Submitted: 2016-03-09
• Status Verified: 2017-04
• Results First Submitted QC: 2017-04-11
• Last Update Submitted: 2017-04-11
• Results First Posted: 2017-05-19
• Last Update Posted: 2017-05-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Olaparib	Olaparib	400mg PO BID Continuous

Primary Outcome Measures

Name	Time	Method
Objective Response Rate of Olaparib	2 years	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

Name	Time	Method
Progression-Free Survival	Two years	Number of patients with progression free survival after two years from starting the trial.
Overall Survival	Two years	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	2 years	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.

Trial Locations

Locations (3)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States