Cytarabine in Treating Young Patients With Recurrent or Refractory Ewing's Sarcoma

• Sponsor: Children's Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00470275
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 10
• Locations: 73
• Arm: 1
• Duration (Months): 79
• Patients Per Site: 0.1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as cytarabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase II trial is studying how well cytarabine works in treating young patients with recurrent or refractory Ewing's sarcoma.

Condition or Disease	Intervention/Treatment	Phase
Sarcoma	Drug: cytarabine	Phase 2

Detailed Description

OBJECTIVES:

• Determine the response rate in younger patients with recurrent or refractory Ewing's sarcoma treated with cytarabine.

OUTLINE: This is a multicenter study.

Patients receive cytarabine IV over 2 hours twice daily on days 1-5. Treatment repeats every 21 days for up to 11 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 5 years.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Intermediate-Dose Cytarabine to Modulate EWS/FLI for Children and Young Adults With Recurrent or Refractory Ewing Sarcoma
• Study Start Date: May 1, 2007
• Actual Primary Completion Date: Aug 1, 2008
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cytarbine Cytarabine IV every 12 hours days 1-5 of 21 day cycle. Response evaluation after 6 cycles of therapy.	Drug: cytarabine; Given IV; Other Names: cytosine arabinoside Ara-C Cytosar NSC #063878

Outcome Measures

Primary Outcome Measures

1. Response [the first six cycles of study chemotherapy (126 days)]

   Any patient who is enrolled and receives at least one dose of cytarabine will be considered evaluable for response if (1) the patient demonstrates progressive disease while on protocol therapy or (2) the patient is observed on protocol therapy for at least one cycle. Patients who achieve a complete or partial response according to the RECIST (Response Evaluation Criteria In Solid Tumors) criteria will be considered responders for the study design. All other patients who are evaluable for response will be considered non-responders for the study.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 30 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

DISEASE CHARACTERISTICS:

• Histologically confirmed Ewing's sarcoma or primitive neuroectodermal tumor (PNET)

• Disease that has recurred or not responded despite prior therapy

• Has declined enrollment on or is not eligible for clinical trial COG-AEWS0521

• Must have at least one site of measurable disease involving lung or soft tissue as documented by CT scan and/or MRI

• No disease limited to bone

PATIENT CHARACTERISTICS:

• Karnofsky performance status (PS) 50-100% (for patients > 16 years of age) OR Lansky PS 50-100% (for patients ≤ 16 years of age)

• Life expectancy ≥ 8 weeks

• ANC ≥ 750/mm^3

• Platelet count ≥ 75,000/mm^{3 (50,000/mm}3 if documented bone marrow metastatic disease) (transfusion independent)

• Hemoglobin ≥ 8.0 g/dL (red blood cell transfusions allowed)

• Bilirubin ≤ 1.5 times upper limit of normal (ULN) for age and < 2.0 mg/dL

• ALT ≤ 2.5 times ULN

• Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR creatinine meeting the following criteria:

• ≤ 0.4 mg/dL (1 month to < 6 months of age)

• ≤ 0.5 mg/dL (6 months to < 1 year of age)

• ≤ 0.6 mg/dL (1 to < 2 years of age)

• ≤ 0.8 mg/dL (2 to < 6 years of age)

• ≤ 1.0 mg/dL (6 to < 10 years of age)

• ≤ 1.2 mg/dL (10 to < 13 years of age)

• ≤ 1.4 mg/dL (≥ 13 years of age) (female)

• ≤ 1.5 mg/dL (13 to < 16 years of age) (male)

• ≤ 1.7 mg/dL (≥ 16 years of age) (male)

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No uncontrolled infection, including systemic fungal infections requiring ongoing antifungal therapy

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• Recovered from all prior tumor-directed therapy

• At least 7 days since prior biologic therapy or immunotherapy

• At least 1 week since prior hematopoietic growth factors (2 weeks for pegfilgrastim)

• At least 2 weeks since prior myelosuppressive chemotherapy

• At least 2 weeks since prior local palliative (small-port) radiotherapy

• At least 6 weeks since prior substantial bone marrow radiotherapy

• At least 6 months since prior radiotherapy to ≥ 50% of the pelvis

• At least 6 months since prior autologous stem cell transplantation

• No prior allogeneic stem cell transplantation

• No prior cytarabine

• No other concurrent investigational agents, including chemotherapy, immunotherapy, or biologic therapy

• No other concurrent anticancer chemotherapy or immunomodulating agents

• Concurrent corticosteroids allowed

• No concurrent intrathecal chemotherapy

• Concurrent radiotherapy to localized painful lesions allowed provided at least one measurable lesion is not irradiated (no irradiated lesion may be used to assess tumor response)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Lurleen Wallace Comprehensive Cancer at University of Alabama - Birmingham	Birmingham	Alabama	United States	35294
2	Arizona Cancer Center at University of Arizona Health Sciences Center	Tucson	Arizona	United States	85724-5024
3	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
4	Southern California Permanente Medical Group	Downey	California	United States	90242-2814
5	Children's Hospital Central California	Madera	California	United States	93638-8762
6	Children's Hospital of Orange County	Orange	California	United States	92868
7	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California	United States	94115
8	Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center	Farmington	Connecticut	United States	06360-2875
9	Lombardi Comprehensive Cancer Center at Georgetown University Medical Center	Washington	District of Columbia	United States	20007
10	Lee Cancer Care of Lee Memorial Health System	Fort Myers	Florida	United States	33901
11	All Children's Hospital	St. Petersburg	Florida	United States	33701
12	St. Joseph's Cancer Institute at St. Joseph's Hospital	Tampa	Florida	United States	33607
13	Kaplan Cancer Center at St. Mary's Medical Center	West Palm Beach	Florida	United States	33407
14	Cancer Research Center of Hawaii	Honolulu	Hawaii	United States	96813
15	Children's Memorial Hospital - Chicago	Chicago	Illinois	United States	60614
16	Simmons Cooper Cancer Institute	Springfield	Illinois	United States	62794-9677
17	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202-5289
18	Lucille P. Markey Cancer Center at University of Kentucky	Lexington	Kentucky	United States	40536-0093
19	Tulane Cancer Center Office of Clinical Research	Alexandria	Louisiana	United States	71315-3198
20	Alvin and Lois Lapidus Cancer Institute at Sinai Hospital	Baltimore	Maryland	United States	21215
21	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
22	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
23	C.S. Mott Children's Hospital at University of Michigan Medical Center	Ann Arbor	Michigan	United States	48109-0286
24	Hurley Medical Center	Flint	Michigan	United States	48503
25	Butterworth Hospital at Spectrum Health	Grand Rapids	Michigan	United States	49503-2560
26	University of Mississippi Cancer Clinic	Jackson	Mississippi	United States	39216-4505
27	Children's Mercy Hospital	Kansas City	Missouri	United States	64108
28	Siteman Cancer Center at Barnes-Jewish St. Peters Hospital - Saint Louis	St. Louis	Missouri	United States	63110
29	Sunrise Hospital and Medical Center	Las Vegas	Nevada	United States	89109-2306
30	Hackensack University Medical Center Cancer Center	Hackensack	New Jersey	United States	07601
31	Overlook Hospital	Morristown	New Jersey	United States	07962
32	Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School	New Brunswick	New Jersey	United States	08903
33	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87131-5636
34	NYU Cancer Institute at New York University Medical Center	New York	New York	United States	10016
35	Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center	New York	New York	United States	10032
36	Stony Brook University Cancer Center	Stony Brook	New York	United States	11794-9446
37	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina	United States	27599-7295
38	Blumenthal Cancer Center at Carolinas Medical Center	Charlotte	North Carolina	United States	28232-2861
39	Akron Children's Hospital	Akron	Ohio	United States	44308-1062
40	Rainbow Babies and Children's Hospital	Cleveland	Ohio	United States	44106-5000
41	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio	United States	44195
42	Columbus Children's Hospital	Columbus	Ohio	United States	43205-2696
43	Children's Medical Center - Dayton	Dayton	Ohio	United States	45404-1815
44	Oklahoma University Cancer Institute	Oklahoma City	Oklahoma	United States	73104
45	Legacy Emanuel Hospital and Health Center and Children's Hospital	Portland	Oregon	United States	97227
46	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033-0850
47	Rhode Island Hospital Comprehensive Cancer Center	Providence	Rhode Island	United States	02903
48	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina	United States	29425
49	Palmetto Health South Carolina Cancer Center	Columbia	South Carolina	United States	29203
50	Greenville Hospital Cancer Center	Greenville	South Carolina	United States	29605
51	East Tennessee Children's Hospital	Knoxville	Tennessee	United States	37901
52	Texas Tech University Health Sciences Center School of Medicine - Amarillo	Amarillo	Texas	United States	79106
53	Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas	United States	75390
54	Cook Children's Medical Center - Fort Worth	Fort Worth	Texas	United States	76104
55	Baylor University Medical Center - Houston	Houston	Texas	United States	77030-2399
56	M. D. Anderson Cancer Center at University of Texas	Houston	Texas	United States	77030-4009
57	Methodist Children's Hospital of South Texas	San Antonio	Texas	United States	78229-3993
58	Primary Children's Medical Center	Salt Lake City	Utah	United States	84113-1100
59	Children's Hospital of The King's Daughters	Norfolk	Virginia	United States	23507-1971
60	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington	United States	98105
61	West Virginia University Health Sciences Center - Charleston	Charleston	West Virginia	United States	25302
62	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin	United States	54449
63	Midwest Children's Cancer Center	Milwaukee	Wisconsin	United States	53226
64	Princess Margaret Hospital for Children	Perth	Western Australia	Australia	6001
65	University of Alberta Hospital	Edmonton	Alberta	Canada	T6G 1Z2
66	IWK Health Centre	Halifax	Nova Scotia	Canada	B3K 6R8
67	McMaster Children's Hospital at Hamilton Health Sciences	Hamilton	Ontario	Canada	L8N 3Z5
68	Children's Hospital of Eastern Ontario	Ottawa	Ontario	Canada	K1H 8L1
69	Hospital for Sick Children	Toronto	Ontario	Canada	M5G 1X8
70	Montreal Children's Hospital at McGill University Health Center	Montreal	Quebec	Canada	H3H 1P3
71	Hopital Sainte Justine	Montreal	Quebec	Canada	H3T 1C5
72	Centre Hospitalier Universitaire de Quebec	Quebec		Canada	G1V 4G2
73	San Jorge Children's Hospital	Santurce		Puerto Rico	00912

Sponsors and Collaborators

• Children's Oncology Group
• National Cancer Institute (NCI)

Investigators

• Study Chair: Kimberly Stegmaier, MD, Dana-Farber Cancer Institute
• Principal Investigator: Holcombe E. Grier, MD, Dana-Farber Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Children's Oncology Group
• ClinicalTrials.gov Identifier: NCT00470275
• Other Study ID Numbers: AEWS0621; CDR0000542650; COG-AEWS0621
• First Posted: May 7, 2007
• Last Update Posted: Oct 20, 2014
• Last Verified: Oct 1, 2014

• Keywords provided by Children's Oncology Group: recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor
• Additional relevant MeSH terms: Sarcoma; Sarcoma, Ewing; Cytarabine

Study Results

Participant Flow

Arm/Group Title	Cytarbine
Arm/Group Description	Cytarabine IV every 12 hours days 1-5 of 21 day cycle. Response evaluation after 6 cycles of therapy.
Period Title: Overall Study
STARTED	10
COMPLETED	0
NOT COMPLETED	10

Baseline Characteristics

Arm/Group Title	Cytarbine
Arm/Group Description	Cytarabine IV every 12 hours days 1-5 of 21 day cycle. Response evaluation after 6 cycles of therapy.
Overall Participants	10
Age (Count of Participants)
<=18 years	4 40%
Between 18 and 65 years	6 60%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	3 30%
Male	7 70%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 20%
Not Hispanic or Latino	7 70%
Unknown or Not Reported	1 10%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	8 80%
More than one race	0 0%
Unknown or Not Reported	2 20%
Region of Enrollment (participants) [Number]
United States	8 80%
Canada	2 20%

Outcome Measures

1. Primary Outcome

Title	Response
Description	Any patient who is enrolled and receives at least one dose of cytarabine will be considered evaluable for response if (1) the patient demonstrates progressive disease while on protocol therapy or (2) the patient is observed on protocol therapy for at least one cycle. Patients who achieve a complete or partial response according to the RECIST (Response Evaluation Criteria In Solid Tumors) criteria will be considered responders for the study design. All other patients who are evaluable for response will be considered non-responders for the study.
Time Frame	the first six cycles of study chemotherapy (126 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cytarabine
Arm/Group Description	Cytarabine IV every 12 hours days 1-5 of 21 day cycle. Response evaluation after 6 cycles of therapy.
Measure Participants	10
Non Responder	10 100%
Responder	0 0%

Adverse Events

Arm/Group Title	Cytarabine
Arm/Group Description	Cytarabine IV every 12 hours days 1-5 of 21 day cycle. Response evaluation after 6 cycles of therapy.
All Cause Mortality
	Cytarabine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Cytarabine
	Affected / at Risk (%)	# Events
Total	2/10 (20%)
Investigations
Neutrophil count decreased	1/10 (10%)
Platelet count decreased	1/10 (10%)
Respiratory, thoracic and mediastinal disorders
Hypoxia	1/10 (10%)
Respiratory, thoracic and mediastinal disorders - Other, specify	1/10 (10%)
Other (Not Including Serious) Adverse Events
	Cytarabine
	Affected / at Risk (%)	# Events
Total	10/10 (100%)
Blood and lymphatic system disorders
Anemia	5/10 (50%)
Febrile neutropenia	4/10 (40%)
Eye disorders
Eye disorders - Other	1/10 (10%)
Photophobia	1/10 (10%)
Gastrointestinal disorders
Abdominal pain	1/10 (10%)
Constipation	1/10 (10%)
Esophageal pain	1/10 (10%)
Esophagitis	1/10 (10%)
Nausea	1/10 (10%)
Oral pain	1/10 (10%)
Vomiting	2/10 (20%)
General disorders
Chills	1/10 (10%)
Facial pain	1/10 (10%)
Fever	2/10 (20%)
Non-cardiac chest pain	1/10 (10%)
Pain	1/10 (10%)
Immune system disorders
Anaphylaxis	1/10 (10%)
Infections and infestations
Conjunctivitis infective	1/10 (10%)
Infections and infestations - Other	5/10 (50%)
Investigations
Alanine aminotransferase increased	4/10 (40%)
Aspartate aminotransferase increased	2/10 (20%)
Blood bilirubin increased	1/10 (10%)
Creatinine increased	1/10 (10%)
Lymphocyte count decreased	3/10 (30%)
Neutrophil count decreased	8/10 (80%)
Platelet count decreased	8/10 (80%)
White blood cell decreased	4/10 (40%)
Metabolism and nutrition disorders
Hyperglycemia	3/10 (30%)
Hypoalbuminemia	1/10 (10%)
Hypocalcemia	1/10 (10%)
Hypokalemia	1/10 (10%)
Hypomagnesemia	1/10 (10%)
Hyponatremia	2/10 (20%)
Musculoskeletal and connective tissue disorders
Back pain	1/10 (10%)
Chest wall pain	1/10 (10%)
Nervous system disorders
Headache	1/10 (10%)
Nervous system disorders - Other	1/10 (10%)
Reproductive system and breast disorders
Uterine hemorrhage	1/10 (10%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/10 (10%)
Epistaxis	1/10 (10%)
Skin and subcutaneous tissue disorders
Alopecia	1/10 (10%)
Rash maculo-papular	1/10 (10%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Must obtain prior Sponsor approval.