Ewing's Sarcoma
Conditions
Keywords
Recurrent, Metastatic
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.
Interventions
DRUGOlaparib
400mg PO BID Continuous
Sponsors
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Olaparib Patients with metastatic Ewing sarcoma who had previously received at least one line of chemotherapy were enrolled. | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | Olaparib |
|---|---|
| Age, Continuous | 30.5 years STANDARD_DEVIATION 15.38 |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 11 / 12 |
| serious Total, serious adverse events | 2 / 12 |
Outcome results
Primary
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.
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Olaparib | Objective Response Rate of Olaparib | 0 Participants |
Secondary
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.
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Olaparib | Number of Participants Experiencing a Grade 3 or 4 Clinically Significant and Related Adverse Event | 4 Participants |
Secondary
Overall Survival
Number of patients survived for 2 years after enrolling onto this study.
Time frame: Two years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Olaparib | Overall Survival | 1 Participants |
Secondary
Progression-Free Survival
Number of patients with progression free survival after two years from starting the trial.
Time frame: Two years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Olaparib | Progression-Free Survival | 0 Participants |