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A Phase III Randomized Trial of Adding Vincristine-Topotecan-Cyclophosphamide to Standard Chemotherapy in Initial Treatment of Non-Metastatic Ewing Sarcoma


Phase 3
N/A
50 Years
Open (Enrolling)
Both
Adult Supratentorial Primitive Neuroectodermal Tumor (PNET), Childhood Supratentorial Primitive Neuroectodermal Tumor, Ewing Sarcoma of Bone, Extraosseous Ewing Sarcoma, Extraosseous Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Peripheral Primitive Neuroectodermal Tumor of the Kidney, Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor

Thank you

Trial Information

A Phase III Randomized Trial of Adding Vincristine-Topotecan-Cyclophosphamide to Standard Chemotherapy in Initial Treatment of Non-Metastatic Ewing Sarcoma


PRIMARY OBJECTIVES:

l. To test the effect of the combination of vincristine, cyclophosphamide, and topotecan
(VTC) added to the standard 5-drug chemotherapy interval-compressed backbone on event-free
survival (EFS) and overall survival of children and young adults with Ewing sarcoma.

SECONDARY OBJECTIVES:

I. To evaluate initial volumetric tumor size as a prognostic factor for EFS in patients with
localized Ewing tumors.

II. To evaluate histologic response as a prognostic factor for EFS in patients with
localized Ewing tumors.

III. To continue evaluation of biologic markers both as related to prognosis and as eventual
therapeutic targets via encouraging concurrent enrollment on a Ewing sarcoma
specimen-collection study.

IV. To evaluate imaging response by FDG-positron emission tomography (PET) as a prognostic
factor for EFS.

V. To evaluate the effects of the type of local therapy on EFS and overall survival.

VI. To evaluate the effect of local surgical margins in conjunction with histologic response
on EFS in patients with localized Ewing tumors.

VII. To evaluate the effect of local therapy modality (surgery, radiotherapy, or a
combination) as well as the type of surgical reconstruction on musculoskeletal
complications.

OUTLINE: This is a multicenter study. Patients are stratified according to age (≤ 17 years
vs ≥ 18 years) and primary tumor site (pelvic vs non-pelvic vs extra-osseous). Patients are
randomized to 1 of 2 treatment arms.

ARM I:

INDUCTION THERAPY: Patients receive vincristine sulfate IV on day 1 in weeks 1, 2, 5, 6, 9,
and 10; doxorubicin hydrochloride IV on days 1 and 2 and cyclophosphamide IV over 30-60
minutes on day 1 in weeks 1, 5, and 9; and ifosfamide IV over 1 hour and etoposide IV over
1-2 hours on days 1-5 in weeks 3, 7, and 11.

CONSOLIDATION THERAPY: Patients receive vincristine sulfate on day 1 in weeks 1, 2, 7, 8,
9,10,13,14, 17,18, 21, and 22; doxorubicin hydrochloride IV on days 1 and 2 in weeks 1 and
9; cyclophosphamide IV over 30-60 minutes on day 1 in weeks 1, 7, 9, 13, 17, and 21; and
ifosfamide IV over 1 hour and etoposide IV over 1-2 hours on days 1-5 in weeks 3, 5, 11, 15,
and 19.

ARM II:

INDUCTION THERAPY: Patients receive vincristine sulfate IV on day 1 in weeks 1, 2, 5, 6,
9,10,11 and 12; topotecan hydrochloride IV over 30 minutes on days 1-5 in weeks 1 and 9;
cyclophosphamide IV over 15-60 minutes on days 1-5 in weeks 1 and 9, and on day 1 of weeks 5
and 11; ifosfamide and etoposide as in arm I; and doxorubicin hydrochloride IV on days 1 and
2 in weeks 5 and 11.

CONSOLIDATION THERAPY: Patients receive vincristine sulfate IV on day 1 in weeks 1, 2, 7-10,
13-16, 19, and 20; topotecan hydrochloride IV over 30 minutes on days 1-5 in weeks 1, 7, and
15; cyclophosphamide IV over 15-60 minutes on days 1-5 in weeks 1, 7, and 15, and on day 1
in weeks 9, 13, and 19; ifosfamide IV over 1 hour and etoposide IV over 1- 2 hours on days
1-5 in weeks 3, 5, 11, 17, and 21; and doxorubicin hydrochloride IV on days 1 and 2 in weeks
9,13, and 19.

Patients with responsive or stable disease undergo may undergo surgery alone in week 13 if
lesion can be complete resected with negative margins and with reasonable functional result.
Patients with unresectable lesions or inadequate margins after surgery receive radiotherapy
during weeks 1-7. Patients with bulky lesions in surgically difficult sites such as the
spine, skull, and periacetabular pelvis, patients with a poor response to induction
chemotherapy, or those patients in whom surgery would result in unacceptable functional
results may undergo radiotherapy alone in weeks 1-7 of consolidation therapy, and surgery
should be performed after completion of consolidation chemotherapy. Patients with
microscopic residual disease after planned pre-operative radiotherapy receive additional
radiotherapy.

After completion of study therapy, patients are followed up periodically for 10 years.


Inclusion Criteria:



- Newly diagnosed extracranial, non-metastatic Ewing sarcoma or primitive
neuroectodermal tumors of bone or soft tissue

- For the purpose of this study, any of the following are considered localized
disease:

- Chest wall tumors with ipsilateral pleural effusions

- Ipsilateral positive pleural fluid cytology

- Ipsilateral pleural-based secondary tumor nodules

- Regional node involvement, based on clinical suspicion confirmed by pathologic
documentation, are considered to be non-metastatic disease

- Tumors arising in the bony skull (extra-dural) are considered to be extracranial

- No evidence of metastatic disease, including the following:

- Lesions that are discontinuous from the primary tumor, are not regional lymph
nodes, and do not share a body cavity with the primary tumor

- Contralateral pleural effusion and contralateral pleural nodules

- Distant lymph node involvement

- Pulmonary nodules that meet the following criteria:

- Solitary nodule > 0.5 cm or multiple nodules of > 0.3 cm unless biopsied
and negative for Ewing sarcoma

- Biopsies of solitary nodule < 0.5 cm or multiple nodules < 3.0 cm (are not
required but if performed) positive for metastatic disease

- No tumors arising in the intra-dural soft tissue

- Creatinine clearance or radioisotope GFR ≥ 70 mL/min OR serum creatinine based on age
and/or gender as follows:

- 0.4 mg/dL (1 month to < 6 months of age)

- 0.5 mg/dL (6 months to < 1 year of age)

- 0.6 mg/dL (1 year to < 2 years of age)

- 0.8 mg/dL (2 years to < 6 years of age)

- 1.0 mg/dL (6 years to < 10 years of age)

- 1.2 mg/dL (10 years to < 13 years of age)

- 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 years to < 16 years of age)

- 1.7 mg/dL (male) or 1.4 mg/dL (female) (≥ 16 years of age)

- Total bilirubin < 1.5 times upper limit of normal (ULN)

- AST or ALT < 2.5 times ULN

- Shortening fraction of ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by
radionuclide angiogram

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception for the duration of study treatment

- No prior chemotherapy or radiotherapy

- Prior biopsy of the primary tumor without an attempt at complete or partial resection
allowed

- Patients are still allowed if unplanned excision was attempted or accomplished
as long as adequate imaging was obtained prior to surgery

- No other concurrent chemotherapy or immunomodulating agents (including steroids
unless used as an antiemetic)

- No concurrent sargramostim (GM-CSF)

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Event-free survival (EFS)

Outcome Time Frame:

Time from study enrollment to disease progression, appearance of disease at sites considered previously uninvolved, diagnosis of a second malignant neoplasm, death or last patient contact, assessed up to 10 years

Safety Issue:

No

Principal Investigator

Mason Bond

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Oncology Group

Authority:

United States: Institutional Review Board

Study ID:

AEWS1031

NCT ID:

NCT01231906

Start Date:

November 2010

Completion Date:

Related Keywords:

  • Adult Supratentorial Primitive Neuroectodermal Tumor (PNET)
  • Childhood Supratentorial Primitive Neuroectodermal Tumor
  • Ewing Sarcoma of Bone
  • Extraosseous Ewing Sarcoma
  • Extraosseous Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
  • Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
  • Peripheral Primitive Neuroectodermal Tumor of the Kidney
  • Untreated Childhood Supratentorial Primitive Neuroectodermal Tumor
  • Kidney Neoplasms
  • Neuroectodermal Tumors
  • Neuroectodermal Tumors, Primitive
  • Sarcoma, Ewing's
  • Neuroectodermal Tumors, Primitive, Peripheral
  • Sarcoma
  • Osteosarcoma

Name

Location

Baylor College of Medicine Houston, Texas  77030
Johns Hopkins University Baltimore, Maryland  21205
Cleveland Clinic Foundation Cleveland, Ohio  44195
Roswell Park Cancer Institute Buffalo, New York  14263
Mayo Clinic Rochester, Minnesota  55905
University of Iowa Hospitals and Clinics Iowa City, Iowa  52242
University of Mississippi Medical Center Jackson, Mississippi  39216-4505
Washington University School of Medicine Saint Louis, Missouri  63110
Fox Chase Cancer Center Philadelphia, Pennsylvania  19111
Medical University of South Carolina Charleston, South Carolina  29425-0721
Tripler Army Medical Center Honolulu, Hawaii  96859-5000
Hurley Medical Center Flint, Michigan  48503
Rhode Island Hospital Providence, Rhode Island  02903
Medical City Dallas Hospital Dallas, Texas  75230
University of Texas Health Science Center at San Antonio San Antonio, Texas  78284-7811
Midwest Children's Cancer Center Milwaukee, Wisconsin  53226
Sinai Hospital of Baltimore Baltimore, Maryland  21225
Bronson Methodist Hospital Kalamazoo, Michigan  49007
Geisinger Medical Center Danville, Pennsylvania  17822-0001
Vanderbilt-Ingram Cancer Center Nashville, Tennessee  37232-6838
Loyola University Medical Center Maywood, Illinois  60153
Massachusetts General Hospital Cancer Center Boston, Massachusetts  02114
Morristown Memorial Hospital Morristown, New Jersey  07962-1956
Marshfield Clinic Marshfield, Wisconsin  54449
Loma Linda University Medical Center Loma Linda, California  92354
Baptist Hospital of Miami Miami, Florida  33176-2197
Newark Beth Israel Medical Center Newark, New Jersey  07112
New York Medical College Valhalla, New York  10595
Dana-Farber Cancer Institute Boston, Massachusetts  02115
Cedars-Sinai Medical Center Los Angeles, California  90048
University of Arkansas for Medical Sciences Little Rock, Arkansas  72205
Brooke Army Medical Center Fort Sam Houston, Texas  78234-6200
Madigan Army Medical Center Tacoma, Washington  98431-5048
Eastern Maine Medical Center Bangor, Maine  04401
University of Nebraska Medical Center Omaha, Nebraska  68198-3330
Hackensack University Medical Center Hackensack, New Jersey  07601
Children's Hospital Los Angeles Los Angeles, California  90027-0700
Children's National Medical Center Washington, District of Columbia  20010-2970
All Children's Hospital St. Petersburg, Florida  33701
Advocate Hope Children's Hospital Oak Lawn, Illinois  60453
Saint Jude Midwest Affiliate Peoria, Illinois  61637
Ochsner Clinic Foundation New Orleans, Louisiana  70121
Carolinas Medical Center Charlotte, North Carolina  28232-2861
University of Oklahoma Health Sciences Center Oklahoma City, Oklahoma  73104
Legacy Emanuel Hospital and Health Center Portland, Oregon  97227
St. Jude Children's Research Hospital Memphis, Tennessee  38105-2794
Driscoll Children's Hospital Corpus Christi, Texas  78466
Scott and White Memorial Hospital Temple, Texas  76508
Inova Fairfax Hospital Falls Church, Virginia  22042-3300
Southern California Permanente Medical Group Downey, California  90242
Children's Hospital Central California Madera, California  93638-8762
Kosair Children's Hospital Louisville, Kentucky  40202-3830
Children's Hospital Medical Center of Akron Akron, Ohio  44308
University of Wisconsin Hospital and Clinics Madison, Wisconsin  53792-0001
Overlook Hospital Summit, New Jersey  07902-0220
Mount Sinai Medical Center New York, New York  10029
Cincinnati Children's Hospital Medical Center Cincinnati, Ohio  45229-3039
Primary Children's Medical Center Salt Lake City, Utah  84113-1100
Montefiore Medical Center Bronx, New York  10467-2490
Saint Peter's University Hospital New Brunswick, New Jersey  08901-1780
Rady Children's Hospital - San Diego San Diego, California  92123-4282
Children's Hospitals and Clinics of Minnesota - Minneapolis Minneapolis, Minnesota  55404
University of New Mexico Cancer Center Albuquerque, New Mexico  87131-5636
Nationwide Children's Hospital Columbus, Ohio  43205-2696
Children's Hospital of Pittsburgh of UPMC Pittsburgh, Pennsylvania  15213
Dell Children's Medical Center of Central Texas Austin, Texas  78723
Children's Hospital and Research Center at Oakland Oakland, California  94609-1809
Mary Bridge Children's Hospital and Health Center Tacoma, Washington  98415-0299
Lehigh Valley Hospital - Muhlenberg Bethlehem, Pennsylvania  18017
Presbyterian Hospital Charlotte, North Carolina  28233-3549
Memorial Medical Center Springfield, Illinois  62781
Lee Memorial Health System Fort Myers, Florida  33902
University of Virginia Charlottesville, Virginia  22908
University of Alabama at Birmingham Birmingham, Alabama  35294-3300
Children's Hospital of Alabama Birmingham, Alabama  35233
Connecticut Children's Medical Center Hartford, Connecticut  06106
University of North Carolina Chapel Hill, North Carolina  27599
Duke University Medical Center Durham, North Carolina  27710
University of Florida Gainesville, Florida  32610-0277
University of Rochester Rochester, New York  14642
Nemours Children's Clinic - Pensacola Pensacola, Florida  32504
Helen DeVos Children's Hospital at Spectrum Health Grand Rapids, Michigan  49503
Yale University New Haven, Connecticut  06520
Wayne State University Detroit, Michigan  48202
Mercy Children's Hospital Toledo, Ohio  43608
Legacy Emanuel Children's Hospital Portland, Oregon  97227
BI-LO Charities Children's Cancer Center Greenville, South Carolina  29605
University of Arizona Health Sciences Center Tucson, Arizona  85724
University of Massachusetts Medical School Worcester, Massachusetts  01605
Dartmouth Hitchcock Medical Center Lebanon, New Hampshire  03756
Indiana University Medical Center Indianapolis, Indiana  46202
University Of Vermont Burlington,, Vermont  05403
Albany Medical Center Albany, New York  12208
University of Texas Southwestern Medical Center Dallas, Texas  
University of Kentucky Lexington, Kentucky  40536-0098
UC Davis Comprehensive Cancer Center Sacramento, California  95817
Oregon Health and Science University Portland, Oregon  97201
Virginia Commonwealth University Richmond, Virginia  
David Geffen School of Medicine at UCLA Los Angeles, California  90095
Florida Hospital Orlando, Florida  32803
Memorial Health University Medical Center Savannah, Georgia  31404
University of Chicago Comprehensive Cancer Center Chicago, Illinois  60637-1470
M D Anderson Cancer Center Houston, Texas  77030
Seattle Children's Hospital Seattle, Washington  98105
Froedtert and the Medical College of Wisconsin Milwaukee, Wisconsin  53226
Wake Forest University Health Sciences Winston-Salem, North Carolina  27157
Childrens Memorial Hospital Chicago, Illinois  60614
Kaiser Permanente-Oakland Oakland, California  94611
Lombardi Comprehensive Cancer Center at Georgetown University Washington, District of Columbia  20057
M D Anderson Cancer Center- Orlando Orlando, Florida  32806
University of Hawaii Honolulu, Hawaii  96813
Saint Luke's Mountain States Tumor Institute Boise, Idaho  83712
Saint Vincent Hospital and Health Services Indianapolis, Indiana  46260
Mercy Medical Center-Sioux City Sioux City, Iowa  51104
Saint Luke's Regional Medical Center Sioux City, Iowa  51104
Saint John Hospital and Medical Center Detroit, Michigan  48236
Michigan State University - Breslin Cancer Center East Lansing, Michigan  48824-1313
Saint John's Mercy Medical Center Saint Louis, Missouri  63141
Nevada Cancer Research Foundation CCOP Las Vegas, Nevada  89106
Saint Barnabas Medical Center Livingston, New Jersey  07039
New York University Langone Medical Center New York, New York  10016
Columbia University Medical Center New York, New York  10032
State University of New York Upstate Medical University Syracuse, New York  13210
Mission Hospitals Inc Asheville, North Carolina  28801
Natalie W Bryant Cancer Center Tulsa, Oklahoma  74136
University of California Medical Center At Irvine-Orange Campus Orange, California  92868
University of South Alabama Mobile, Alabama  36693
University of Illinois Chicago, Illinois  60612
Stony Brook University Medical Center Stony Brook, New York  11794
Cook Children's Medical Center Fort Worth, Texas  76104
Memorial Healthcare System - Joe DiMaggio Children's Hospital Hollywood, Florida  33021
West Virginia University Charleston Charleston, West Virginia  25304
The Children's Medical Center of Dayton Dayton, Ohio  45404
Advocate Lutheran General Hospital Park Ridge, Illinois  60068
University of Miami Miller School of Medicine-Sylvester Cancer Center Miami, Florida  33136
University of Minnesota Medical Center-Fairview Minneapolis, Minnesota  55455
C S Mott Children's Hospital Ann Arbor, Michigan  48109
Southern Illinois University Springfield, Illinois  62702
University Of Missouri-Columbia Columbia, Missouri  65212
Siouxland Hematology Oncology Associates Sioux City, Iowa  51101
Riley Hospital for Children Indianapolis, Indiana  46202
UMDNJ - Robert Wood Johnson University Hospital New Brunswick, New Jersey  08903
Phoenix Childrens Hospital Phoenix, Arizona  85016
Miller Children's Hospital Long Beach, California  90806
Childrens Hospital of Orange County Orange, California  92868-3874
Alfred I duPont Hospital for Children Wilmington, Delaware  19803
Nemours Children's Clinic - Jacksonville Jacksonville, Florida  32207-8426
Nemours Childrens Clinic - Orlando Orlando, Florida  32806
Saint Joseph Children's Hospital of Tampa Tampa, Florida  33607
Children's Healthcare of Atlanta - Egleston Atlanta, Georgia  30322
The Childrens Mercy Hospital Kansas City, Missouri  64108
Rainbow Babies and Childrens Hospital Cleveland, Ohio  44106
Penn State Hershey Children's Hospital Hershey, Pennsylvania  17033
Palmetto Health Richland Columbia, South Carolina  29203
East Tennessee Childrens Hospital Knoxville, Tennessee  37916
Children's Hospital and Medical Center of Omaha Omaha, Nebraska  68114
Saint Joseph's Regional Medical Center Paterson, New Jersey  07503
Childrens Hospital-King's Daughters Norfolk, Virginia  23507
Sanford Medical Center-Fargo Fargo, North Dakota  58122
Children's Hospital Colorado Aurora, Colorado  80045
Lucile Packard Children's Hospital Stanford University Palo Alto, California  94304
University of California San Francisco Medical Center-Parnassus San Francisco, California  94143
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center Denver, Colorado  80218
Raymond Blank Children's Hospital Des Moines, Iowa  50309
Children's Hospital-Main Campus New Orleans, Louisiana  70118
The Toledo Hospital/Toledo Children's Hospital Toledo, Ohio  43606
Saint Christopher's Hospital for Children Philadelphia, Pennsylvania  19134
Greenville Cancer Treatment Center Greenville, South Carolina  29605
Sanford USD Medical Center - Sioux Falls Sioux Falls, South Dakota  57117-5134
T C Thompson Children's Hospital Chattanooga, Tennessee  37403
Providence Sacred Heart Medical Center and Children's Hospital Spokane, Washington  99204
Broward Health Medical Center Fort Lauderdale, Florida  33316
The Steven and Alexandra Cohen Children's Medical Center of New York New Hyde Park, New York  11040
Mattel Children's Hospital UCLA Los Angeles, California  90095
Georgia Regents University Augusta, Georgia  30912
Saint John's Hospital Springfield, Illinois  62702