Olaparib in Adults With Recurrent/Metastatic Ewing's Sarcoma

Phase II Study of the PARP Inhibitor, Olaparib, in Adult Patients With Recurrent/Metastatic Ewing's Sarcoma Following Failure of Prior Chemotherapy

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.

Study Overview

• Status: Completed
• Conditions: Ewing's Sarcoma
• Intervention / Treatment: Drug: Olaparib

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 Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02215
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02115
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Olaparib; 400mg PO BID Continuous	Drug: Olaparib; 400mg PO BID Continuous; Other Names: AZD 2281

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival	Number of patients with progression free survival after two years from starting the trial.	Two years
Overall Survival	Number of patients survived for 2 years after enrolling onto this study.	Two years
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.	2 years

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Edwin Choy, MD PhD, Massachusetts General Hospital

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (ACTUAL): January 1, 2014
• Study Completion (ACTUAL): November 1, 2014

Study Registration Dates

• First Submitted: April 18, 2012
• First Submitted That Met QC Criteria: April 23, 2012
• First Posted (ESTIMATE): April 24, 2012

Study Record Updates

• Last Update Posted (ACTUAL): May 19, 2017
• Last Update Submitted That Met QC Criteria: April 11, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: Metastatic; Recurrent
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Sarcoma; Sarcoma, Ewing; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors; Olaparib
• Other Study ID Numbers: 11-470

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO