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

NCT00061893 | Completed Phase 2 Results DMC

• 2 other identifiers: AEWS02P1CDR0000302409
• Study Type: interventional
• Target: 38
• Locations: 4 countries
• Sites: 101

Brief Summary

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.

Conditions

Sarcoma

Keywords

metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Event Free Survival

  24 months after start of protocol therapy

Study Arms (1)

Combination chemotherapy

EXPERIMENTAL

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; 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

Interventions

celecoxib DRUG

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. \[Celecoxib may be interrupted for up to 7 days around the time of surgical procedures.\] .

Combination chemotherapy

cyclophosphamide DRUG

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.

Combination chemotherapy

doxorubicin hydrochloride DRUG

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.

Combination chemotherapy

etoposide DRUG

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.

Combination chemotherapy

ifosfamide DRUG

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.

Combination chemotherapy

vinblastine sulfate DRUG

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. \[Vinblastine may be interrupted for up to 7 days around the time of surgical procedures.\]

Combination chemotherapy

vincristine sulfate DRUG

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.

Combination chemotherapy

conventional surgery PROCEDURE

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)

Combination chemotherapy

radiation therapy RADIATION

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)

Combination chemotherapy

MESNA DRUG

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.

Combination chemotherapy

Filgrastim DRUG

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.

Also known as: G-CSF

Combination chemotherapy

Eligibility Criteria

• Age: Up to 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

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

Study Sites (101)

University of Alabama at Birmingham Comprehensive Cancer Center

Birmingham, Alabama, 35294, United States

Location

Phoenix Children's Hospital

Phoenix, Arizona, 85016-7710, United States

Location

Arkansas Cancer Research Center at University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Southern California Permanente Medical Group

Downey, California, 90242-2814, United States

Location

Loma Linda University Cancer Institute at Loma Linda University Medical Center

Loma Linda, California, 92354, United States

Location

Jonathan Jaques Children's Cancer Center at Miller Children's Hospital

Long Beach, California, 90801, United States

Location

Childrens Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Children's Hospital Central California

Madera, California, 93638-8762, United States

Location

University of California Davis Cancer Center

Sacramento, California, 95817, United States

Location

Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center

Farmington, Connecticut, 06360-2875, United States

Location

Alfred I. duPont Hospital for Children

Wilmington, Delaware, 19899, United States

Location

Lee Cancer Care of Lee Memorial Health System

Fort Myers, Florida, 33901, United States

Location

Nemours Children's Clinic

Jacksonville, Florida, 32207, United States

Location

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Florida Hospital Cancer Institute at Florida Hospital Orlando

Orlando, Florida, 32803-1273, United States

Location

Nemours Children's Clinic - Orlando

Orlando, Florida, 32806, United States

Location

Sacred Heart Cancer Center at Sacred Heart Hospital

Pensacola, Florida, 32504, United States

Location

All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

St. Joseph's Cancer Institute at St. Joseph's Hospital

Tampa, Florida, 33607, United States

Location

Kaplan Cancer Center at St. Mary's Medical Center

West Palm Beach, Florida, 33407, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

MBCCOP - Medical College of Georgia Cancer Center

Augusta, Georgia, 30912-3730, United States

Location

Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center

Savannah, Georgia, 31403-3089, United States

Location

Southern Illinois University School of Medicine

Springfield, Illinois, 62794-9620, United States

Location

Indiana University Cancer Center

Indianapolis, Indiana, 46202-5289, United States

Location

St. Vincent Indianapolis Hospital

Indianapolis, Indiana, 46260, United States

Location

Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center

Kansas City, Kansas, 66160-7357, United States

Location

Markey Cancer Center at University of Kentucky Chandler Medical Center

Lexington, Kentucky, 40536-0293, United States

Location

Kosair Children's Hospital

Louisville, Kentucky, 40232, United States

Location

CancerCare of Maine at Eastern Maine Medial Center

Bangor, Maine, 04401, United States

Location

Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

C.S. Mott Children's Hospital at University of Michigan

Ann Arbor, Michigan, 48109-0238, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201-1379, United States

Location

Hurley Medical Center

Flint, Michigan, 48503, United States

Location

Spectrum Health Hospital - Butterworth Campus

Grand Rapids, Michigan, 49503-2560, United States

Location

Van Elslander Cancer Center at St. John Hospital and Medical Center

Grosse Pointe Woods, Michigan, 48236, United States

Location

Children's Hospitals and Clinics of Minneapolis

Minneapolis, Minnesota, 55404, United States

Location

University of Minnesota Medical Center & Children's Hospital - Fairview

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic Cancer Center

Rochester, Minnesota, 55905, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216-4505, United States

Location

Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Siteman Cancer Center at Barnes-Jewish Hospital

St Louis, Missouri, 63110, United States

Location

Sunrise Hospital and Medical Center

Las Vegas, Nevada, 89109-2306, United States

Location

Hackensack University Medical Center Cancer Center

Hackensack, New Jersey, 07601, United States

Location

Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School

New Brunswick, New Jersey, 08903, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263-0001, United States

Location

Herbert Irving Comprehensive Cancer Center at Columbia University

New York, New York, 10032, United States

Location

James P. Wilmot Cancer Center at University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

SUNY Upstate Medical University Hospital

Syracuse, New York, 13210, United States

Location

Albert Einstein Cancer Center at Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

Location

New York Medical College

Valhalla, New York, 10595, United States

Location

Blumenthal Cancer Center at Carolinas Medical Center

Charlotte, North Carolina, 28232-2861, United States

Location

Presbyterian Cancer Center at Presbyterian Hospital

Charlotte, North Carolina, 28233-3549, United States

Location

Children's Hospital Medical Center of Akron

Akron, Ohio, 44308-1062, United States

Location

Rainbow Babies and Children's Hospital

Cleveland, Ohio, 44106-5000, United States

Location

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44195-5217, United States

Location

Columbus Children's Hospital

Columbus, Ohio, 43205-2696, United States

Location

Children's Medical Center - Dayton

Dayton, Ohio, 45404-1815, United States

Location

Medical University of Ohio Cancer Center

Toledo, Ohio, 43614, United States

Location

Tod Children's Hospital - Forum Health

Youngstown, Ohio, 44501, United States

Location

OU Cancer Institute

Oklahoma City, Oklahoma, 73104, United States

Location

Legacy Emanuel Hospital and Health Center & Children's Hospital

Portland, Oregon, 97227, United States

Location

Penn State Cancer Institute at Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033-0850, United States

Location

St. Christopher's Hospital for Children

Philadelphia, Pennsylvania, 19134-1095, United States

Location

Hollings Cancer Center at Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Palmetto Health South Carolina Cancer Center

Columbia, South Carolina, 29203, United States

Location

Greenville Hospital System Cancer Center

Greenville, South Carolina, 29605, United States

Location

East Tennessee Children's Hospital

Knoxville, Tennessee, 37916, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232-6310, United States

Location

Texas Tech University Health Sciences Center School of Medicine - Amarillo

Amarillo, Texas, 79106, United States

Location

Medical City Dallas Hospital

Dallas, Texas, 75230, United States

Location

Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas

Dallas, Texas, 75390, United States

Location

Cook Children's Medical Center - Fort Worth

Fort Worth, Texas, 76104-9958, United States

Location

Baylor University Medical Center - Houston

Houston, Texas, 77030-2399, United States

Location

Methodist Children's Hospital of South Texas

San Antonio, Texas, 78229-3993, United States

Location

CCOP - Scott and White Hospital

Temple, Texas, 76508, United States

Location

Primary Children's Medical Center

Salt Lake City, Utah, 84113-1100, United States

Location

INOVA Fairfax Hospital

Fairfax, Virginia, 22031, United States

Location

Children's Hospital of The King's Daughters

Norfolk, Virginia, 23507-1971, United States

Location

Virginia Commonwealth University Massey Cancer Center

Richmond, Virginia, 23298-0037, United States

Location

Carilion Cancer Center of Western Virginia

Roanoke, Virginia, 24029, United States

Location

Providence Cancer Center at Sacred Heart Medical Center

Spokane, Washington, 99220-2555, United States

Location

West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division

Charleston, West Virginia, 25302, United States

Location

Edwards Comprehensive Cancer Center at Cabell Huntington Hospital

Huntington, West Virginia, 25701, United States

Location

St. Vincent Hospital Regional Cancer Center

Green Bay, Wisconsin, 54307-3508, United States

Location

Marshfield Clinic - Marshfield Center

Marshfield, Wisconsin, 54449, United States

Location

Midwest Children's Cancer Center

Milwaukee, Wisconsin, 53226, United States

Location

Westmead Institute for Cancer Research at Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

University of Alberta Hospital

Edmonton, Alberta, T6G 1Z2, Canada

Location

Children's & Women's Hospital of British Columbia

Vancouver, British Columbia, V6H 3V4, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

IWK Health Centre

Halifax, Nova Scotia, B3K 6R8, Canada

Location

McMaster Children's Hospital at Hamilton Health Sciences

Hamilton, Ontario, L8N 3Z5, Canada

Location

Cancer Centre of Southeastern Ontario at Kingston General Hospital

Kingston, Ontario, K7L 3N6, Canada

Location

Children's Hospital of Eastern Ontario

Ottawa, Ontario, K1H 8L1, Canada

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Montreal Children's Hospital at McGill University Health Center

Montreal, Quebec, H3H 1P3, Canada

Location

Hopital Sainte Justine

Montreal, Quebec, H3T 1C5, Canada

Location

Saskatoon Cancer Centre at the University of Saskatchewan

Saskatoon, Saskatchewan, S7N 4H4, Canada

Location

Centre Hospitalier Universitaire de Quebec

Québec, G1V 4G2, Canada

Location

San Jorge Children's Hospital

Santurce, 00912, Puerto Rico

Location

Related Publications (1)

• 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.

  PMID: 23065953 RESULT

MeSH Terms

Conditions

Sarcoma; Neuroectodermal Tumors, Primitive, Peripheral

Interventions

Celecoxib; Cyclophosphamide; Doxorubicin; Etoposide; Ifosfamide; Vinblastine; Vincristine; Radiotherapy; Mesna; Filgrastim; Granulocyte Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Oxazines; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Therapeutics; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfonic Acids; Sulfur Acids; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Results Reporting Coordinator
• Organization: Children's Oncology Group

resultsreportingcoordinator@childrensoncologygroup.org

Study Officials

• Judy L. Felgenhauer, MD, PS

  Sacred Heart Children's Hospital

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2003
• First Posted: June 6, 2003
• Study Start: April 1, 2004
• Primary Completion: April 1, 2008
• Study Completion: December 1, 2013
• Last Updated: February 15, 2019
• Results First Posted: March 12, 2013

Record last verified: 2019-01

Locations

PR (1); AU (1); CA (12); US (87)