Olaparib in Adults With Recurrent/Metastatic Ewing's Sarcoma

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT01583543
• Collaborator: (none)
• Enrollment: 12
• Locations: 3
• Arm: 1
• Duration (Months): 30
• Patients Per Site: 4
• Patients Per Site Per Month: 0.1

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Ewing's Sarcoma	Drug: Olaparib	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: May 1, 2012
• Actual Primary Completion Date: Jan 1, 2014
• Actual Study Completion Date: Nov 1, 2014

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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

1. Progression-Free Survival [Two years]

   Number of patients with progression free survival after two years from starting the trial.

2. Overall Survival [Two years]

   Number of patients survived for 2 years after enrolling onto this study.

3. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02115
2	Brigham and Women's Hospital	Boston	Massachusetts	United States	02215
3	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215

Sponsors and Collaborators

• Massachusetts General Hospital

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Edwin Choy, MD, Principal Investigator, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT01583543
• Other Study ID Numbers: 11-470
• First Posted: Apr 24, 2012
• Last Update Posted: May 19, 2017
• Last Verified: Apr 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Edwin Choy, MD, Principal Investigator, Massachusetts General Hospital: Recurrent; Metastatic
• Additional relevant MeSH terms: Sarcoma; Sarcoma, Ewing; Olaparib

Study Results

Participant Flow

Arm/Group Title	Olaparib
Arm/Group Description	Patients with metastatic Ewing sarcoma who had previously received at least one line of chemotherapy were enrolled.
Period Title: Overall Study
STARTED	12
COMPLETED	12
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Olaparib
Arm/Group Description	Patients with metastatic Ewing sarcoma who had previously received at least one line of chemotherapy were enrolled.
Overall Participants	12
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	30.5 (15.38)
Sex: Female, Male (Count of Participants)
Female	2 16.7%
Male	10 83.3%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Olaparib
Arm/Group Description	Patients with metastatic Ewing sarcoma who had previously received at least one line of chemotherapy were enrolled.
Measure Participants	12
Count of Participants [Participants]	0 0%

2. Secondary Outcome

Title	Progression-Free Survival
Description	Number of patients with progression free survival after two years from starting the trial.
Time Frame	Two years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Olaparib
Arm/Group Description	This group of patients with metastatic Ewing sarcoma received single agent olaparib.
Measure Participants	12
Count of Participants [Participants]	0 0%

3. Secondary Outcome

Title	Overall Survival
Description	Number of patients survived for 2 years after enrolling onto this study.
Time Frame	Two years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Olaparib
Arm/Group Description	This group of patients with metastatic Ewing sarcoma received single agent olaparib therapy.
Measure Participants	12
Count of Participants [Participants]	1 8.3%

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Olaparib
Arm/Group Description	400mg PO BID Continuous Olaparib: 400mg PO BID Continuous
Measure Participants	12
Count of Participants [Participants]	4 33.3%

Adverse Events

Time Frame	From initiation of study drug, throughout the study, and for 30 days after the last dose of study drug.
Arm/Group Title	Olaparib
Arm/Group Description	400 mg PO BID Continuous Olaparib
All Cause Mortality
	Olaparib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Olaparib
	Affected / at Risk (%)	# Events
Total	2/12 (16.7%)
General disorders
Death	2/12 (16.7%)
Respiratory, thoracic and mediastinal disorders
hemoptysis	1/12 (8.3%)
Other (Not Including Serious) Adverse Events
	Olaparib
	Affected / at Risk (%)	# Events
Total	11/12 (91.7%)
Blood and lymphatic system disorders
Anemia	2/12 (16.7%)
Leukopenia	1/12 (8.3%)
Gastrointestinal disorders
Abdominal pain	1/12 (8.3%)
Constipation	1/12 (8.3%)
Diarrhea	2/12 (16.7%)
Dry mouth	2/12 (16.7%)
Dyspepsia	1/12 (8.3%)
Dysphagia	1/12 (8.3%)
Nausea	5/12 (41.7%)
Stomach pain	1/12 (8.3%)
Vomiting	4/12 (33.3%)
Sensitive teeth	1/12 (8.3%)
General disorders
Edema - limbs	2/12 (16.7%)
Fatigue	3/12 (25%)
Fever	2/12 (16.7%)
Non-cardiac chest pain	2/12 (16.7%)
Pain	4/12 (33.3%)
Immune system disorders
Allergies	1/12 (8.3%)
Infections and infestations
Pneumonia	1/12 (8.3%)
Upper respiratory infection	1/12 (8.3%)
Urinary tract infection	2/12 (16.7%)
Infection, other	2/12 (16.7%)
Injury, poisoning and procedural complications
Food poisoning	1/12 (8.3%)
Investigations
Lymphopenia	1/12 (8.3%)
Thrombocytopenia	2/12 (16.7%)
Metabolism and nutrition disorders
Hypoglycemia	1/12 (8.3%)
Anorexia	1/12 (8.3%)
Polydipsia	1/12 (8.3%)
Musculoskeletal and connective tissue disorders
Back pain	2/12 (16.7%)
Pain - other	3/12 (25%)
Nervous system disorders
Dizziness	1/12 (8.3%)
Dysgeusia	1/12 (8.3%)
headache	1/12 (8.3%)
Psychiatric disorders
Anxiety	2/12 (16.7%)
Insomnia	2/12 (16.7%)
Renal and urinary disorders
Urinary hesitancy	1/12 (8.3%)
Reproductive system and breast disorders
Perinea/ Genital numbness	1/12 (8.3%)
Respiratory, thoracic and mediastinal disorders
Cough	3/12 (25%)
Dyspnea	1/12 (8.3%)
Hypoxia	1/12 (8.3%)
Postnasal drip	1/12 (8.3%)
Skin and subcutaneous tissue disorders
Erythema multiforme	1/12 (8.3%)
Rash maculo-papular	2/12 (16.7%)
Cellulitis	1/12 (8.3%)
Vascular disorders
Flushing	1/12 (8.3%)
Hot flashes	1/12 (8.3%)
Lymphedema	1/12 (8.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.