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

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

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.

Study Overview

• Status: Completed
• Conditions: Sarcoma
• Intervention / Treatment: 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

Detailed Description

OBJECTIVES:

• Determine the feasibility and safety of low-dose vinblastine and celecoxib in combination with standard multiagent chemotherapy in patients with newly diagnosed metastatic Ewing's sarcoma family of tumors.
• Determine the event-free survival of patients treated with this regimen.
• Determine the pharmacokinetics of this regimen in these patients.

OUTLINE: This is a pilot, multicenter study.

• Induction therapy: Patients receive the following alternating regimens:

  • VAC (courses 1 and 3): Patients receive vincristine IV and cyclophosphamide IV over 1 hour on day 1 and doxorubicin IV continuously on days 1 and 2 of weeks 1 and 7.
  • IE (courses 2 and 4): Patients receive ifosfamide IV over 1 hour and etoposide IV over 1-2 hours on days 1-5 of weeks 4 and 10.

Patients also receive filgrastim (G-CSF) subcutaneously (SC) beginning 24-48 hours after the last dose of chemotherapy and continuing until blood counts recover.

Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity.

• Local control and consolidation therapy: Beginning on week 13, patients are assigned to 1 of 4 regimens based on disease status.

  • Regimen A (surgery only): Patients who respond to induction chemotherapy undergo surgery on week 13. Patients then begin consolidation therapy on week 15 with the following alternating regimens:

    • VAC (courses 5, 7, and 9): Patients receive VAC on weeks 15, 21, and 27.
    • IE (courses 6, 8, 10, 12, and 14): Patients receive IE on weeks 18, 24, 30, 36, and 42.
    • VC (courses 11 and 13): Patients receive vincristine IV and cyclophosphamide IV over 1 hour on weeks 33 and 39.

  • Regimen B (radiotherapy only): Patients with unresectable lesions undergo radiotherapy once daily 5 days a week for up to approximately 6 weeks beginning on week 13. Patients also receive consolidation therapy beginning on week 13, with the following alternating regimens:

    • VAC (courses 5, 9, and 11): Patients receive VAC on weeks 13, 25, and 31.
    • IE (courses 6, 8, 10, 12, and 14): Patients receive IE on weeks 16, 22, 28, 34, and 40.
    • VC (courses 7 and 13): Patients receive VC on weeks 19 and 37.

  • Regimen C (surgery and radiotherapy): Patients who respond to induction chemotherapy undergo surgery on week 13. Patients who have inadequate margins after surgery undergo radiotherapy (as in regimen B) beginning on week 15. Patients also receive consolidation therapy, beginning on week 15, with the following alternating regimens:

    • VAC (courses 5, 9, and 11): Patients receive VAC on weeks 15, 27, and 33.
    • IE (courses 6, 8, 10, 12, and 14): Patients receive IE on weeks 18, 24, 30, 36, and 42.
    • VC (courses 7 and 13): Patients receive VC on weeks 21 and 39.

  • Regimen D (preoperative radiotherapy): Patients with bulky lesions who do not have a good clinical and radiographic response to induction therapy begin consolidation therapy on week 13 with VAC (course 5) and undergo concurrent radiotherapy as in regimen B. Patients then receive IE on weeks 16 and 19 for courses 6 and 7. Patients undergo surgery on week 22. Patients continue consolidation therapy with the following alternating regimens:

    • VAC (courses 8 and 9): Patients receive VAC on weeks 24 and 27.
    • IE (courses 10, 12, and 14): Patients receive IE on weeks 30, 36, and 42.
    • VC (courses 11 and 13): Patients receive VC on weeks 33 and 39. Patients receive G-CSF SC (as in induction therapy) during all consolidation courses.

Consolidation therapy continues for 10 courses in the absence of disease progression or unacceptable toxicity.

• Vinblastine and celecoxib therapy: Throughout induction, local control, and consolidation therapies, patients also receive vinblastine IV 3 times a week (twice a week during the weeks that vincristine is given) and oral celecoxib twice daily, beginning on day 1 of course 1 and continuing until the completion of course 14.* NOTE: *To assess for safety, the first 6 patients enrolled receive vinblastine only during courses 1 and 2 and celecoxib is then added for all subsequent courses.

Patients are followed every 3 months for 3 years and then every 6 months for 2 years.

PROJECTED ACCRUAL: A total of 6-36 patients will be accrued for this study within 1.17 years.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 50 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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 Names: G-CSF

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of Severe Toxicity	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.	The first two cycles (6 weeks) of protocol chemotherapy

Secondary Outcome Measures

Outcome Measure	Time Frame
Event Free Survival	24 months after start of protocol therapy

Collaborators and Investigators

• Sponsor: Children's Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Judy L. Felgenhauer, MD, PS, Sacred Heart Children's Hospital

Publications and helpful links

General Publications

• Felgenhauer JL, Nieder ML, Krailo MD, Bernstein ML, Henry DW, Malkin D, Baruchel S, Chuba PJ, Sailer SL, Brown K, Ranganathan S, Marina N. A pilot study of low-dose anti-angiogenic chemotherapy in combination with standard multiagent chemotherapy for patients with newly diagnosed metastatic Ewing sarcoma family of tumors: A Children's Oncology Group (COG) Phase II study NCT00061893. Pediatr Blood Cancer. 2013 Mar;60(3):409-14. doi: 10.1002/pbc.24328. Epub 2012 Oct 12.

Study record dates

Study Major Dates

• Study Start: April 1, 2004
• Primary Completion (Actual): April 1, 2008
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: June 5, 2003
• First Submitted That Met QC Criteria: June 5, 2003
• First Posted (Estimate): June 6, 2003

Study Record Updates

• Last Update Posted (Actual): February 15, 2019
• Last Update Submitted That Met QC Criteria: January 29, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Osteosarcoma; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Sarcoma; Sarcoma, Ewing; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Cyclooxygenase 2 Inhibitors; Cyclophosphamide; Etoposide; Ifosfamide; Celecoxib; Doxorubicin; Liposomal doxorubicin; Vincristine; Vinblastine
• Other Study ID Numbers: AEWS02P1; CDR0000302409 (Registry Identifier: PDQ (Physician Data Query))