Vinblastine, Celecoxib, and Combination Chemotherapy in Treating Patients With Newly-Diagnosed Metastatic Ewing's Sarcoma Family of Tumors

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00061893
First received: June 5, 2003
Last updated: September 16, 2014
Last verified: September 2014
  Purpose

RATIONALE: Drugs used in chemotherapy, such as vinblastine, work in different ways to stop tumor cells from dividing so they stop growing or die. Celecoxib may stop the growth of Ewing's sarcoma by stopping blood flow to the tumor. Combining more than one chemotherapy drug with celecoxib may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining low-dose vinblastine and celecoxib with standard regimens of combination chemotherapy in treating patients who have newly-diagnosed metastatic Ewing's sarcoma family of tumors.


Condition Intervention Phase
Sarcoma
Drug: celecoxib
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: etoposide
Drug: ifosfamide
Drug: vinblastine sulfate
Drug: vincristine sulfate
Procedure: conventional surgery
Radiation: radiation therapy
Drug: MESNA
Drug: Filgrastim
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of Low-Dose Antiangiogenic Chemotherapy in Combination With Standard Multiagent Chemotherapy for Patients With Newly Diagnosed Metastatic Ewing Sarcoma Family of Tumors

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Occurrence of Severe Toxicity [ Time Frame: The first two cycles (6 weeks) of protocol chemotherapy ] [ Designated as safety issue: Yes ]
    An incidence of severe toxicity is defined to be the occurrence of grade 3 or higher infection or grade 3 or higher sensory neuropathy during cycles 1-2 of protocol therapy. If 12 or more patients experience grade 3 or higher infection or five or more patients experience grade 3 or higher sensory neuropathy during cycles 1-2 of protocol therapy, the regimen will be flagged as being associated with an excessive rate of severe toxicity.


Secondary Outcome Measures:
  • Event Free Survival [ Time Frame: 24 months after start of protocol therapy ] [ Designated as safety issue: No ]

Enrollment: 38
Study Start Date: April 2004
Study Completion Date: December 2013
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Combination chemotherapy
Metastatic Ewing Sarcoma - 14-cycle study building on conventional tx (cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, ifosfamide, etoposide) and adding two antiangiogenic agents: the vinca alkaloid vinblastine and the cyclooxygenase-2 inhibitor celecoxib. Refer to the Interventions section for dosages, method of delivery and frequency of administration.
Drug: celecoxib
Given orally, Celecoxib 250 mg/m2 PO BID (500mg/m2/day) from Day 1 of Cycle 1 through Day 21 of Cycle 14. The dose should be rounded off to the nearest 100 mg. If PK studies are being done, Celecoxib should be given 24 hours prior to the other drugs for Cycle 1 only. [Celecoxib may be interrupted for up to 7 days around the time of surgical procedures.] .
Drug: cyclophosphamide
Given IV, 1200 mg/m2 IV infusion over 1 hour with MESNA uroprotection, on Day 1. For children < 1 year treat with 50% doses calculated on a m2 basis. If tolerated (no delay in administration of the next cycle due to delayed count recovery or delayed resolution of other toxicities and no serious toxicities), consider increasing to 75% and then to 100% of the calculated full dose.
Drug: doxorubicin hydrochloride
Given IV, Doxorubicin 75 mg/ m2 /course continuous IV infusion over 48 hours, beginning Day 1. Note: The total doxorubicin dose per cycle is 75 mg/ m2, which will be given as 37.5 mg/m2/day x 2 days. Doxorubicin may be given as a continuous infusion or brief infusion.
Drug: etoposide
Given IV, Vincristine 2 mg/m2 IV push, on Day 1. Maximum dose 2 mg. For children < 1 year treat with 50% doses calculated on a m2 basis. If tolerated (no delay in administration of the next cycle due to delayed count recovery or delayed resolution of other toxicities and no serious toxicities), consider increasing to 75% and then to 100% of the calculated full dose.
Drug: ifosfamide
Given IV,Ifosfamide 1800 mg/m2 /day IV infusion over 1 hour, Days 1-5 of each cycle. (9,000 mg/m2 max total dose per cycle). Prehydrate for 6 hours, 1,000 ml/m2 total volume (165 ml/m2/hour for 6 hours). For children < 1 year treat with 50% doses calculated on a m2 basis. If tolerated (no delay in administration of the next cycle due to delayed count recovery or delayed resolution of other toxicities and no serious toxicities), consider increasing to 75% and then to 100% of the calculated full dose.
Drug: vinblastine sulfate
Given IV, Vinblastine 1 mg/m2/d IV push three times per week beginning Day 1 of Cycle 1 and continuing through Day 21 of Cycle 14. In weeks during which vincristine is given, hold one dose of vinblastine and administer only 2 doses of vinblastine during that week. If vinblastine is due the same day as vincristine, hold that dose of vinblastine. [Vinblastine may be interrupted for up to 7 days around the time of surgical procedures.]
Drug: vincristine sulfate
Given IV, Vincristine 2 mg/m2 IV push, on Day 1. Maximum dose 2 mg. For children < 1 year treat with 50% doses calculated on a m2 basis. If tolerated (no delay in administration of the next cycle due to delayed count recovery or delayed resolution of other toxicities and no serious toxicities), consider increasing to 75% and then to 100% of the calculated full dose.
Procedure: conventional surgery
Patients who respond to induction chemotherapy undergo surgery on week 13. Patients who have inadequate margins after surgery undergo radiotherapy beginning on week 15. (see Detailed Description for frequency of administration and groups evaluated)
Radiation: radiation therapy
Patients with unresectable lesions undergo radiotherapy 5 days a week for approximately 6 weeks beginning on week 13. (see Detailed Description for frequency of administration and groups evaluated)
Drug: MESNA
The total daily MESNA dose is equal to at least 60% of the daily cyclophosphamide or ifosfamide dose, or by continuous infusion of the 60% dose. MESNA continuous infusion should be started at the same time as the cyclophosphamide/ifosfamide and be completed no sooner than 8 hours after the end of the cyclophosphamide or ifosfamide infusion. The oral dose of MESNA is 2x the IV dose. Patients able to tolerate oral MESNA may receive the final dose by mouth at 40% of the oxazaphosphorine (cyclophosphamide or ifosfamide) dose. The dose should be given two hours earlier than the IV dose would be given. Additionally, if the patient vomits within two hours after the oral dose, the dose should be repeated or IV MESNA given.
Drug: Filgrastim
G-CSF (Filgrastim) 5 micrograms/kg/day subcutaneously beginning 24 to 48 hours after the last dose of chemotherapy, and continuing until the absolute neutrophil count is 2,000/µL or greater after nadir.
Other Name: G-CSF

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Newly diagnosed Ewing's sarcoma family of tumors of the bone or soft tissues

    • Paraspinal tumors of extra-dural origin and Askin's tumor of the chest wall are eligible
  • Metastatic disease, defined by the following criteria:

    • Lesions are discontinuous from the primary tumor, are not regional lymph nodes, and do not share a body cavity with the primary tumor
    • A single pulmonary or pleural nodule greater than 1 cm OR multiple nodules greater than 0.5 cm are considered evidence of pulmonary or pleural metastases (unless there is another clear medical explanation for these lesions)
    • Contralateral pleural effusions are considered metastatic disease
  • No CNS involvement

PATIENT CHARACTERISTICS:

Age

  • 50 and under (at diagnosis)

Performance status

  • Lansky 50-100% (under 17 years of age)
  • Karnofsky 50-100% (age 17 and over)

    • Patients whose performance status is affected by a pathological fracture are allowed provided they are able to undergo treatment

Life expectancy

  • Not specified

Hematopoietic

  • Not specified

Hepatic

  • Bilirubin no greater than 1.5 times upper limit of normal (ULN)
  • AST or ALT less than 5 times ULN

Renal

  • Creatinine adjusted according to age as follows*:

    • No greater than 0.4 mg/dL (≤ 5 months)
    • No greater than 0.5 mg/dL (6 months -11 months)
    • No greater than 0.6 mg/dL (1 year-23 months)
    • No greater than 0.8 mg/dL (2 years-5 years)
    • No greater than 1.0 mg/dL (6 years-9 years)
    • No greater than 1.2 mg/dL (10 years-12 years)
    • No greater than 1.4 mg/dL (13 years and over [female])
    • No greater than 1.5 mg/dL (13 years to 15 years [male])
    • No greater than 1.7 mg/dL (16 years and over [male]) OR
  • Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min* NOTE: *Unless these values are related to renal insufficiency secondary to tumor involvement that is expected to improve once the tumor mass is smaller (e.g., pelvic mass causing obstructive hydronephrosis)

Cardiovascular

  • Shortening fraction at least 27% by echocardiogram OR
  • Ejection fraction at least 50% by MUGA

Other

  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • Body surface area at least 0.4 m^2
  • No allergy to sulfa
  • No aspirin hypersensitivity
  • No asthma triad (asthma with nasal polyps, and urticaria)
  • No other prior cancer, including nonmelanoma skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No prior bone marrow or stem cell transplantation

Chemotherapy

  • No prior chemotherapy

Endocrine therapy

  • Not specified

Radiotherapy

  • No prior radiotherapy

Surgery

  • Not specified

Other

  • No other concurrent nonsteroidal anti-inflammatory medications, including salicylates
  • No concurrent dexrazoxane unless approved by the study investigator
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00061893

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Locations
United States, Alabama
University of Alabama at Birmingham Comprehensive Cancer Center
Birmingham, Alabama, United States, 35294
United States, Arizona
Phoenix Children's Hospital
Phoenix, Arizona, United States, 85016-7710
United States, Arkansas
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States, 72205
United States, California
Southern California Permanente Medical Group
Downey, California, United States, 90242-2814
Loma Linda University Cancer Institute at Loma Linda University Medical Center
Loma Linda, California, United States, 92354
Jonathan Jaques Children's Cancer Center at Miller Children's Hospital
Long Beach, California, United States, 90801
Childrens Hospital Los Angeles
Los Angeles, California, United States, 90027
Children's Hospital Central California
Madera, California, United States, 93638-8762
University of California Davis Cancer Center
Sacramento, California, United States, 95817
United States, Connecticut
Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center
Farmington, Connecticut, United States, 06360-2875
United States, Delaware
Alfred I. duPont Hospital for Children
Wilmington, Delaware, United States, 19899
United States, Florida
Lee Cancer Care of Lee Memorial Health System
Fort Myers, Florida, United States, 33901
Nemours Children's Clinic
Jacksonville, Florida, United States, 32207
University of Miami Sylvester Comprehensive Cancer Center
Miami, Florida, United States, 33136
Florida Hospital Cancer Institute at Florida Hospital Orlando
Orlando, Florida, United States, 32803-1273
Nemours Children's Clinic - Orlando
Orlando, Florida, United States, 32806
Sacred Heart Cancer Center at Sacred Heart Hospital
Pensacola, Florida, United States, 32504
All Children's Hospital
St. Petersburg, Florida, United States, 33701
St. Joseph's Cancer Institute at St. Joseph's Hospital
Tampa, Florida, United States, 33607
Kaplan Cancer Center at St. Mary's Medical Center
West Palm Beach, Florida, United States, 33407
United States, Georgia
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States, 30322
MBCCOP - Medical College of Georgia Cancer Center
Augusta, Georgia, United States, 30912-3730
Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
Savannah, Georgia, United States, 31403-3089
United States, Illinois
Southern Illinois University School of Medicine
Springfield, Illinois, United States, 62794-9620
United States, Indiana
Indiana University Cancer Center
Indianapolis, Indiana, United States, 46202-5289
St. Vincent Indianapolis Hospital
Indianapolis, Indiana, United States, 46260
United States, Kansas
Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
Kansas City, Kansas, United States, 66160-7357
United States, Kentucky
Markey Cancer Center at University of Kentucky Chandler Medical Center
Lexington, Kentucky, United States, 40536-0293
Kosair Children's Hospital
Louisville, Kentucky, United States, 40232
United States, Maine
CancerCare of Maine at Eastern Maine Medial Center
Bangor, Maine, United States, 04401
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
C.S. Mott Children's Hospital at University of Michigan
Ann Arbor, Michigan, United States, 48109-0238
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
Hurley Medical Center
Flint, Michigan, United States, 48503
Spectrum Health Hospital - Butterworth Campus
Grand Rapids, Michigan, United States, 49503-2560
Van Elslander Cancer Center at St. John Hospital and Medical Center
Grosse Pointe Woods, Michigan, United States, 48236
United States, Minnesota
Children's Hospitals and Clinics of Minneapolis
Minneapolis, Minnesota, United States, 55404
University of Minnesota Medical Center & Children's Hospital - Fairview
Minneapolis, Minnesota, United States, 55455
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216-4505
United States, Missouri
Children's Mercy Hospital
Kansas City, Missouri, United States, 64108
Siteman Cancer Center at Barnes-Jewish Hospital
St. Louis, Missouri, United States, 63110
United States, Nevada
Sunrise Hospital and Medical Center
Las Vegas, Nevada, United States, 89109-2306
United States, New Jersey
Hackensack University Medical Center Cancer Center
Hackensack, New Jersey, United States, 07601
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
New Brunswick, New Jersey, United States, 08903
United States, New York
Albert Einstein Cancer Center at Albert Einstein College of Medicine
Bronx, New York, United States, 10461
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
Herbert Irving Comprehensive Cancer Center at Columbia University
New York, New York, United States, 10032
James P. Wilmot Cancer Center at University of Rochester Medical Center
Rochester, New York, United States, 14642
SUNY Upstate Medical University Hospital
Syracuse, New York, United States, 13210
New York Medical College
Valhalla, New York, United States, 10595
United States, North Carolina
Blumenthal Cancer Center at Carolinas Medical Center
Charlotte, North Carolina, United States, 28232-2861
Presbyterian Cancer Center at Presbyterian Hospital
Charlotte, North Carolina, United States, 28233-3549
United States, Ohio
Children's Hospital Medical Center of Akron
Akron, Ohio, United States, 44308-1062
Rainbow Babies and Children's Hospital
Cleveland, Ohio, United States, 44106-5000
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195-5217
Columbus Children's Hospital
Columbus, Ohio, United States, 43205-2696
Children's Medical Center - Dayton
Dayton, Ohio, United States, 45404-1815
Medical University of Ohio Cancer Center
Toledo, Ohio, United States, 43614
Tod Children's Hospital - Forum Health
Youngstown, Ohio, United States, 44501
United States, Oklahoma
OU Cancer Institute
Oklahoma City, Oklahoma, United States, 73104
United States, Oregon
Legacy Emanuel Hospital and Health Center & Children's Hospital
Portland, Oregon, United States, 97227
United States, Pennsylvania
Penn State Cancer Institute at Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
St. Christopher's Hospital for Children
Philadelphia, Pennsylvania, United States, 19134-1095
United States, South Carolina
Hollings Cancer Center at Medical University of South Carolina
Charleston, South Carolina, United States, 29425
Palmetto Health South Carolina Cancer Center
Columbia, South Carolina, United States, 29203
Greenville Hospital System Cancer Center
Greenville, South Carolina, United States, 29605
United States, Tennessee
East Tennessee Children's Hospital
Knoxville, Tennessee, United States, 37916
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232-6310
United States, Texas
Texas Tech University Health Sciences Center School of Medicine - Amarillo
Amarillo, Texas, United States, 79106
Medical City Dallas Hospital
Dallas, Texas, United States, 75230
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
Dallas, Texas, United States, 75390
Cook Children's Medical Center - Fort Worth
Fort Worth, Texas, United States, 76104-9958
Baylor University Medical Center - Houston
Houston, Texas, United States, 77030-2399
Methodist Children's Hospital of South Texas
San Antonio, Texas, United States, 78229-3993
CCOP - Scott and White Hospital
Temple, Texas, United States, 76508
United States, Utah
Primary Children's Medical Center
Salt Lake City, Utah, United States, 84113-1100
United States, Virginia
INOVA Fairfax Hospital
Fairfax, Virginia, United States, 22031
Children's Hospital of The King's Daughters
Norfolk, Virginia, United States, 23507-1971
Virginia Commonwealth University Massey Cancer Center
Richmond, Virginia, United States, 23298-0037
Carilion Cancer Center of Western Virginia
Roanoke, Virginia, United States, 24029
United States, Washington
Providence Cancer Center at Sacred Heart Medical Center
Spokane, Washington, United States, 99220-2555
United States, West Virginia
West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division
Charleston, West Virginia, United States, 25302
Edwards Comprehensive Cancer Center at Cabell Huntington Hospital
Huntington, West Virginia, United States, 25701
United States, Wisconsin
St. Vincent Hospital Regional Cancer Center
Green Bay, Wisconsin, United States, 54307-3508
Marshfield Clinic - Marshfield Center
Marshfield, Wisconsin, United States, 54449
Midwest Children's Cancer Center
Milwaukee, Wisconsin, United States, 53226
Australia, New South Wales
Westmead Institute for Cancer Research at Westmead Hospital
Westmead, New South Wales, Australia, 2145
Canada, Alberta
University of Alberta Hospital
Edmonton, Alberta, Canada, T6G 1Z2
Canada, British Columbia
Children's & Women's Hospital of British Columbia
Vancouver, British Columbia, Canada, V6H 3V4
Canada, Manitoba
CancerCare Manitoba
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, Nova Scotia
IWK Health Centre
Halifax, Nova Scotia, Canada, B3K 6R8
Canada, Ontario
McMaster Children's Hospital at Hamilton Health Sciences
Hamilton, Ontario, Canada, L8N 3Z5
Cancer Centre of Southeastern Ontario at Kingston General Hospital
Kingston, Ontario, Canada, K7L 3N6
Children's Hospital of Eastern Ontario
Ottawa, Ontario, Canada, K1H 8L1
Hospital for Sick Children
Toronto, Ontario, Canada, M5G 1X8
Canada, Quebec
Montreal Children's Hospital at McGill University Health Center
Montreal, Quebec, Canada, H3H 1P3
Hopital Sainte Justine
Montreal, Quebec, Canada, H3T 1C5
Canada, Saskatchewan
Saskatoon Cancer Centre at the University of Saskatchewan
Saskatoon, Saskatchewan, Canada, S7N 4H4
Canada
Centre Hospitalier Universitaire de Quebec
Quebec, Canada, G1V 4G2
Puerto Rico
San Jorge Children's Hospital
Santurce, Puerto Rico, 00912
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Judy L. Felgenhauer, MD, PS Sacred Heart Children's Hospital
  More Information

Additional Information:
Publications:
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00061893     History of Changes
Other Study ID Numbers: AEWS02P1, CDR0000302409
Study First Received: June 5, 2003
Results First Received: January 17, 2013
Last Updated: September 16, 2014
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor

Additional relevant MeSH terms:
Sarcoma
Sarcoma, Ewing
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Osteosarcoma
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Cyclophosphamide
Celecoxib
Ifosfamide
Isophosphamide mustard
Liposomal doxorubicin
Doxorubicin
Etoposide
Vincristine
Vinblastine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors

ClinicalTrials.gov processed this record on September 29, 2014