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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


Phase 2
N/A
50 Years
Not Enrolling
Both
Sarcoma

Thank you

Trial Information

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


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Occurrence of Severe Toxicity

Outcome Description:

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.

Outcome Time Frame:

Duration of Protocol Therapy

Safety Issue:

Yes

Principal Investigator

Judy L. Felgenhauer, MD, PS

Investigator Role:

Study Chair

Investigator Affiliation:

Sacred Heart Children's Hospital

Authority:

United States: Federal Government

Study ID:

AEWS02P1

NCT ID:

NCT00061893

Start Date:

April 2004

Completion Date:

April 2008

Related Keywords:

  • Sarcoma
  • metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor
  • Sarcoma, Ewing's
  • Neuroectodermal Tumors, Primitive, Peripheral
  • Sarcoma

Name

Location

Roswell Park Cancer InstituteBuffalo, New York  14263
Mayo Clinic Cancer CenterRochester, Minnesota  55905
Indiana University Cancer CenterIndianapolis, Indiana  46202-5265
Barbara Ann Karmanos Cancer InstituteDetroit, Michigan  48201
University of Mississippi Medical CenterJackson, Mississippi  39216-4505
Hurley Medical CenterFlint, Michigan  48503
Medical City Dallas HospitalDallas, Texas  75230
Midwest Children's Cancer CenterMilwaukee, Wisconsin  53226
Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health CenterFarmington, Connecticut  06360-2875
Van Elslander Cancer Center at St. John Hospital and Medical CenterGrosse Pointe Woods, Michigan  48236
Penn State Cancer Institute at Milton S. Hershey Medical CenterHershey, Pennsylvania  17033-0850
Vanderbilt-Ingram Cancer CenterNashville, Tennessee  37232-6838
Marshfield Clinic - Marshfield CenterMarshfield, Wisconsin  54449
University of Alabama at Birmingham Comprehensive Cancer CenterBirmingham, Alabama  35294-3300
New York Medical CollegeValhalla, New York  10595
University of Miami Sylvester Comprehensive Cancer CenterMiami, Florida  33136
Siteman Cancer Center at Barnes-Jewish HospitalSaint Louis, Missouri  63110
CCOP - Scott and White HospitalTemple, Texas  76508
Cleveland Clinic Taussig Cancer CenterCleveland, Ohio  44195
Children's Mercy HospitalKansas City, Missouri  64108
University of California Davis Cancer CenterSacramento, California  95817
Nemours Children's ClinicJacksonville, Florida  32207
All Children's HospitalSt. Petersburg, Florida  33701
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer InstituteBoston, Massachusetts  02115
St. Christopher's Hospital for ChildrenPhiladelphia, Pennsylvania  19134-1095
Cook Children's Medical Center - Fort WorthFort Worth, Texas  76104
Inova Fairfax HospitalFalls Church, Virginia  22042-3300
Phoenix Children's HospitalPhoenix, Arizona  85016-7710
Southern California Permanente Medical GroupDowney, California  90242
Children's Hospital Central CaliforniaMadera, California  93638-8762
Southern Illinois University School of MedicineSpringfield, Illinois  62794-9658
Kosair Children's HospitalLouisville, Kentucky  40202-3830
Sunrise Hospital and Medical CenterLas Vegas, Nevada  89109-2306
Children's Hospital Medical Center of AkronAkron, Ohio  44308
Children's Medical Center - DaytonDayton, Ohio  45404
Palmetto Health South Carolina Cancer CenterColumbia, South Carolina  29203
East Tennessee Children's HospitalKnoxville, Tennessee  37901
Children's Hospital of the King's DaughtersNorfolk, Virginia  23507
Arkansas Cancer Research Center at University of Arkansas for Medical SciencesLittle Rock, Arkansas  72205
Kansas Masonic Cancer Research Institute at the University of Kansas Medical CenterKansas City, Kansas  66160-7353
Markey Cancer Center at University of Kentucky Chandler Medical CenterLexington, Kentucky  40536-0084
Herbert Irving Comprehensive Cancer Center at Columbia UniversityNew York, New York  10032
Blumenthal Cancer Center at Carolinas Medical CenterCharlotte, North Carolina  28232-2861
Loma Linda University Cancer Institute at Loma Linda University Medical CenterLoma Linda, California  92354
Jonathan Jaques Children's Cancer Center at Miller Children's HospitalLong Beach, California  90801
Lee Cancer Care of Lee Memorial Health SystemFort Myers, Florida  33901
Nemours Children's Clinic - OrlandoOrlando, Florida  32806
Florida Hospital Cancer Institute at Florida Hospital OrlandoOrlando, Florida  32803-1273
Sacred Heart Cancer Center at Sacred Heart HospitalPensacola, Florida  32504
St. Joseph's Cancer Institute at St. Joseph's HospitalTampa, Florida  33607
Kaplan Cancer Center at St. Mary's Medical CenterWest Palm Beach, Florida  33407
Winship Cancer Institute of Emory UniversityAtlanta, Georgia  30322
Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical CenterSavannah, Georgia  31403-3089
St. Vincent Indianapolis HospitalIndianapolis, Indiana  46260
CancerCare of Maine at Eastern Maine Medial CenterBangor, Maine  04401
C.S. Mott Children's Hospital at University of MichiganAnn Arbor, Michigan  48109-0238
Children's Hospitals and Clinics of MinneapolisMinneapolis, Minnesota  55404
Hackensack University Medical Center Cancer CenterHackensack, New Jersey  07601
Albert Einstein Cancer Center at Albert Einstein College of MedicineBronx, New York  10461
SUNY Upstate Medical University HospitalSyracuse, New York  13210
Presbyterian Cancer Center at Presbyterian HospitalCharlotte, North Carolina  28233-3549
Rainbow Babies and Children's HospitalCleveland, Ohio  44106-5000
Medical University of Ohio Cancer CenterToledo, Ohio  43614
Tod Children's Hospital - Forum HealthYoungstown, Ohio  44501
Legacy Emanuel Hospital and Health Center & Children's HospitalPortland, Oregon  97227
Hollings Cancer Center at Medical University of South CarolinaCharleston, South Carolina  29425
Greenville Hospital System Cancer CenterGreenville, South Carolina  29605
Texas Tech University Health Sciences Center School of Medicine - AmarilloAmarillo, Texas  79106
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - DallasDallas, Texas  75390
Baylor University Medical Center - HoustonHouston, Texas  77030-2399
Methodist Children's Hospital of South TexasSan Antonio, Texas  78229-3993
Primary Children's Medical CenterSalt Lake City, Utah  84113-1100
Carilion Cancer Center of Western VirginiaRoanoke, Virginia  24029
Providence Cancer Center at Sacred Heart Medical CenterSpokane, Washington  99220-2555
West Virginia University - Robert C. Byrd Health Sciences Center - Charleston DivisionCharleston, West Virginia  25302
Edwards Comprehensive Cancer Center at Cabell Huntington HospitalHuntington, West Virginia  25701
St. Vincent Hospital Regional Cancer CenterGreen Bay, Wisconsin  54307-3508
James P. Wilmot Cancer Center at University of Rochester Medical CenterRochester, New York  14642
Childrens Hospital Los AngelesLos Angeles, California  90027
Alfred I. duPont Hospital for ChildrenWilmington, Delaware  19803
MBCCOP - Medical College of Georgia Cancer CenterAugusta, Georgia  30912-3730
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical SchoolNew Brunswick, New Jersey  08903
Virginia Commonwealth University Massey Cancer CenterRichmond, Virginia  23298-0037
Spectrum Health Hospital - Butterworth CampusGrand Rapids, Michigan  49503
Columbus Children's HospitalColumbus, Ohio  43205-2696
University of Minnesota Medical Center & Children's Hospital - FairviewMinneapolis, Minnesota  55455
OU Cancer InstituteOklahoma City, Oklahoma  73104