Vinblastine, Celecoxib, and Combination Chemotherapy in Treating Patients With Newly-Diagnosed Metastatic Ewing's Sarcoma Family of Tumors
- Conditions
- Sarcoma
- Interventions
- Procedure: conventional surgeryRadiation: radiation therapy
- Registration Number
- NCT00061893
- Lead Sponsor
- Children's Oncology Group
- 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 38
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Combination chemotherapy vincristine sulfate 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. Combination chemotherapy conventional surgery 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. Combination chemotherapy vinblastine sulfate 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. Combination chemotherapy radiation therapy 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. Combination chemotherapy Filgrastim 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. Combination chemotherapy celecoxib 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. Combination chemotherapy doxorubicin hydrochloride 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. Combination chemotherapy cyclophosphamide 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. Combination chemotherapy etoposide 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. Combination chemotherapy ifosfamide 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. Combination chemotherapy MESNA 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.
- Primary Outcome Measures
Name Time Method Occurrence of Severe Toxicity The first two cycles (6 weeks) of protocol chemotherapy 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
Name Time Method Event Free Survival 24 months after start of protocol therapy
Trial Locations
- Locations (101)
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School
🇺🇸New Brunswick, New Jersey, United States
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Edwards Comprehensive Cancer Center at Cabell Huntington Hospital
🇺🇸Huntington, West Virginia, United States
Children's & Women's Hospital of British Columbia
🇨🇦Vancouver, British Columbia, Canada
San Jorge Children's Hospital
🇵🇷Santurce, Puerto Rico
Rainbow Babies and Children's Hospital
🇺🇸Cleveland, Ohio, United States
Cleveland Clinic Taussig Cancer Center
🇺🇸Cleveland, Ohio, United States
University of Miami Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
Indiana University Cancer Center
🇺🇸Indianapolis, Indiana, United States
St. Vincent Indianapolis Hospital
🇺🇸Indianapolis, Indiana, United States
University of Minnesota Medical Center & Children's Hospital - Fairview
🇺🇸Minneapolis, Minnesota, United States
Southern California Permanente Medical Group
🇺🇸Downey, California, United States
Southern Illinois University School of Medicine
🇺🇸Springfield, Illinois, United States
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Spectrum Health Hospital - Butterworth Campus
🇺🇸Grand Rapids, Michigan, United States
Hurley Medical Center
🇺🇸Flint, Michigan, United States
Children's Hospitals and Clinics of Minneapolis
🇺🇸Minneapolis, Minnesota, United States
Herbert Irving Comprehensive Cancer Center at Columbia University
🇺🇸New York, New York, United States
Sunrise Hospital and Medical Center
🇺🇸Las Vegas, Nevada, United States
Albert Einstein Cancer Center at Albert Einstein College of Medicine
🇺🇸Bronx, New York, United States
Columbus Children's Hospital
🇺🇸Columbus, Ohio, United States
Presbyterian Cancer Center at Presbyterian Hospital
🇺🇸Charlotte, North Carolina, United States
Medical University of Ohio Cancer Center
🇺🇸Toledo, Ohio, United States
Children's Medical Center - Dayton
🇺🇸Dayton, Ohio, United States
Tod Children's Hospital - Forum Health
🇺🇸Youngstown, Ohio, United States
Hollings Cancer Center at Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Penn State Cancer Institute at Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
St. Christopher's Hospital for Children
🇺🇸Philadelphia, Pennsylvania, United States
Greenville Hospital System Cancer Center
🇺🇸Greenville, South Carolina, United States
Medical City Dallas Hospital
🇺🇸Dallas, Texas, United States
Methodist Children's Hospital of South Texas
🇺🇸San Antonio, Texas, United States
Children's Hospital of The King's Daughters
🇺🇸Norfolk, Virginia, United States
Carilion Cancer Center of Western Virginia
🇺🇸Roanoke, Virginia, United States
St. Vincent Hospital Regional Cancer Center
🇺🇸Green Bay, Wisconsin, United States
McMaster Children's Hospital at Hamilton Health Sciences
🇨🇦Hamilton, Ontario, Canada
Marshfield Clinic - Marshfield Center
🇺🇸Marshfield, Wisconsin, United States
Children's Hospital of Eastern Ontario
🇨🇦Ottawa, Ontario, Canada
Centre Hospitalier Universitaire de Quebec
🇨🇦Quebec, Canada
New York Medical College
🇺🇸Valhalla, New York, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Primary Children's Medical Center
🇺🇸Salt Lake City, Utah, United States
Vanderbilt-Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
University of Alabama at Birmingham Comprehensive Cancer Center
🇺🇸Birmingham, Alabama, United States
Phoenix Children's Hospital
🇺🇸Phoenix, Arizona, United States
Barbara Ann Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
OU Cancer Institute
🇺🇸Oklahoma City, Oklahoma, United States
Legacy Emanuel Hospital and Health Center & Children's Hospital
🇺🇸Portland, Oregon, United States
St. Joseph's Cancer Institute at St. Joseph's Hospital
🇺🇸Tampa, Florida, United States
Mayo Clinic Cancer Center
🇺🇸Rochester, Minnesota, United States
Midwest Children's Cancer Center
🇺🇸Milwaukee, Wisconsin, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
SUNY Upstate Medical University Hospital
🇺🇸Syracuse, New York, United States
Lee Cancer Care of Lee Memorial Health System
🇺🇸Fort Myers, Florida, United States
Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
Loma Linda University Cancer Institute at Loma Linda University Medical Center
🇺🇸Loma Linda, California, United States
CancerCare of Maine at Eastern Maine Medial Center
🇺🇸Bangor, Maine, United States
Jonathan Jaques Children's Cancer Center at Miller Children's Hospital
🇺🇸Long Beach, California, United States
Children's Hospital Central California
🇺🇸Madera, California, United States
Alfred I. duPont Hospital for Children
🇺🇸Wilmington, Delaware, United States
Childrens Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center
🇺🇸Farmington, Connecticut, United States
James P. Wilmot Cancer Center at University of Rochester Medical Center
🇺🇸Rochester, New York, United States
Siteman Cancer Center at Barnes-Jewish Hospital
🇺🇸Saint Louis, Missouri, United States
Children's Hospital Medical Center of Akron
🇺🇸Akron, Ohio, United States
Children's Mercy Hospital
🇺🇸Kansas City, Missouri, United States
Blumenthal Cancer Center at Carolinas Medical Center
🇺🇸Charlotte, North Carolina, United States
Hackensack University Medical Center Cancer Center
🇺🇸Hackensack, New Jersey, United States
CCOP - Scott and White Hospital
🇺🇸Temple, Texas, United States
East Tennessee Children's Hospital
🇺🇸Knoxville, Tennessee, United States
Hopital Sainte Justine
🇨🇦Montreal, Quebec, Canada
Westmead Institute for Cancer Research at Westmead Hospital
🇦🇺Westmead, New South Wales, Australia
Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
Cook Children's Medical Center - Fort Worth
🇺🇸Fort Worth, Texas, United States
West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division
🇺🇸Charleston, West Virginia, United States
Palmetto Health South Carolina Cancer Center
🇺🇸Columbia, South Carolina, United States
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
🇺🇸Dallas, Texas, United States
Montreal Children's Hospital at McGill University Health Center
🇨🇦Montreal, Quebec, Canada
Saskatoon Cancer Centre at the University of Saskatchewan
🇨🇦Saskatoon, Saskatchewan, Canada
CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
IWK Health Centre
🇨🇦Halifax, Nova Scotia, Canada
Nemours Children's Clinic
🇺🇸Jacksonville, Florida, United States
Markey Cancer Center at University of Kentucky Chandler Medical Center
🇺🇸Lexington, Kentucky, United States
Sacred Heart Cancer Center at Sacred Heart Hospital
🇺🇸Pensacola, Florida, United States
Winship Cancer Institute of Emory University
🇺🇸Atlanta, Georgia, United States
Kaplan Cancer Center at St. Mary's Medical Center
🇺🇸West Palm Beach, Florida, United States
All Children's Hospital
🇺🇸Saint Petersburg, Florida, United States
MBCCOP - Medical College of Georgia Cancer Center
🇺🇸Augusta, Georgia, United States
Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
🇺🇸Savannah, Georgia, United States
Virginia Commonwealth University Massey Cancer Center
🇺🇸Richmond, Virginia, United States
Providence Cancer Center at Sacred Heart Medical Center
🇺🇸Spokane, Washington, United States
INOVA Fairfax Hospital
🇺🇸Fairfax, Virginia, United States
Baylor University Medical Center - Houston
🇺🇸Houston, Texas, United States
Van Elslander Cancer Center at St. John Hospital and Medical Center
🇺🇸Grosse Pointe Woods, Michigan, United States
Texas Tech University Health Sciences Center School of Medicine - Amarillo
🇺🇸Amarillo, Texas, United States
Cancer Centre of Southeastern Ontario at Kingston General Hospital
🇨🇦Kingston, Ontario, Canada
Florida Hospital Cancer Institute at Florida Hospital Orlando
🇺🇸Orlando, Florida, United States
University of California Davis Cancer Center
🇺🇸Sacramento, California, United States
Kosair Children's Hospital
🇺🇸Louisville, Kentucky, United States
Nemours Children's Clinic - Orlando
🇺🇸Orlando, Florida, United States
C.S. Mott Children's Hospital at University of Michigan
🇺🇸Ann Arbor, Michigan, United States