Clinical trial NCT01583543: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ewing's Sarcoma
Keywords: Recurrent
Metastatic
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2012-04-24
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Objective Response Rate of Olaparib
timeFrame: 2 years
Secondary outcomes:
measure: Progression-Free Survival
timeFrame: Two years
measure: Overall Survival
timeFrame: Two years
measure: Number of Participants Experiencing a Grade 3 or 4 Clinically Significant and Related Adverse Event
timeFrame: 2 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Edwin Choy, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.