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A Pilot Study to Evaluate Novel Agents (Temozolomide and Cixutumumab [IMC-A12, Anti-IGF-IR Monoclonal Antibody, IND #100947, NSC #742460]) in Combination With Intensive Multi-Agent Interval Compressed Therapy for Patients With High-Risk Rhabdomyosarcoma

1 Month
49 Years
Open (Enrolling)
Adult Rhabdomyosarcoma, Alveolar Childhood Rhabdomyosarcoma, Embryonal Childhood Rhabdomyosarcoma, Metastatic Childhood Soft Tissue Sarcoma, Previously Untreated Childhood Rhabdomyosarcoma, Stage IV Adult Soft Tissue Sarcoma

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Trial Information

A Pilot Study to Evaluate Novel Agents (Temozolomide and Cixutumumab [IMC-A12, Anti-IGF-IR Monoclonal Antibody, IND #100947, NSC #742460]) in Combination With Intensive Multi-Agent Interval Compressed Therapy for Patients With High-Risk Rhabdomyosarcoma


I. To determine the feasibility of administering cixutumumab in combination with an
intensive multi-agent interval compressed chemotherapy regimen for the treatment of
high-risk metastatic rhabdomyosarcoma (RMS).

II. To determine the feasibility of adding temozolomide to vincristine and irinotecan in
these patients.

III. To assess immediate and short-term side effects of concurrent temozolomide,
vincristine, and irinotecan with radiotherapy in these patients.


I. To gain a preliminary estimate of the response rate to cixutumumab or temozolomide,
vincristine, and irinotecan in these patients.

II. To obtain preliminary efficacy data for cixutumumab or temozolomide in combination with
an intensive multi-agent interval compressed chemotherapy regimen in these patients.

III. To determine the effectiveness of detecting metastatic disease with fludeoxyglucose F
18 positron emission tomography (FDG PET) and to compare assessment of response using
standard imaging techniques with response assessed by FDG PET.

IV. To assess changes in serum levels of IGF-I, IGF-II, IGF-BP3 as biomarkers of IGF-IR

OUTLINE: This is a dose-escalation study of cixutumumab. Patients are assigned to 1 of 2
treatment groups according to the timing of their enrollment onto the study.

GROUP 1: Patients receive vincristine sulfate IV on day 1 of weeks 1-5, 7, 8, 11, 12, 15,
16, 20-24, 28, 29, 32, 33, 35, 38, 41-44, 47, 48, 50, and 51; irinotecan hydrochloride IV
over 90 minutes on days 1-5 of weeks 1, 4, 20, 23, 47, and 50; ifosfamide IV over 1 hour and
etoposide IV over 1-2 hours on days 1-5 of weeks 9, 13, 17, 26, and 30; doxorubicin
hydrochloride IV on days 1 and 2 of weeks 7, 11, 15, 28, and 32; cyclophosphamide IV over
30-60 minutes on day 1 of weeks 7, 11, 15, 28, 32, 35, 38, 41, and 44; dactinomycin IV on
day 1 of weeks 35, 38, 41, and 44; and cixutumumab IV over 1 hour on day 1 of weeks 1-51.
Patients also undergo radiotherapy* on days 1-5 of weeks 20-24.

GROUP 2: Patients receive vincristine sulfate, irinotecan hydrochloride, ifosfamide,
etoposide, doxorubicin hydrochloride, cyclophosphamide, and dactinomycin and undergo
radiotherapy* as in group 1. Patients also receive oral temozolomide on days 1-5 of weeks 1,
4, 20, 23, 47, and 50.

GROUP 3: Patients receive vincristine sulfate, irinotecan hydrochloride, ifosfamide,
etoposide, doxorubicin hydrochloride, cyclophosphamide, dactinomycin, and cixutumumab and
undergo radiotherapy* as in group 1. Patients also receive temozolomide as in group 2.
(Discontinued as of January 2013)

NOTE: *Patients with parameningeal tumors and evidence of intracranial extension or those
requiring emergency radiotherapy may receive radiotherapy starting in week 1; cixutumumab
should be withheld during radiotherapy.

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

Inclusion Criteria:

- Newly diagnosed, biopsy-confirmed metastatic rhabdomyosarcoma (RMS) or

- Stage IV, Clinical Group IV

- RMS with parameningeal and paraspinal primary tumors, including those with
intracranial extension by contrast magnetic resonance imaging (MRI) showing that the
primary tumor touches, displaces, invades, distorts, or otherwise causes signal
abnormality of the dura in brain or spinal cord in contiguity to the primary site,
are allowed; ICE is also presumed to exist if the cerebrospinal fluid (CSF)
cytopathology is positive for tumor at diagnosis

- Has undergone initial surgery (including biopsy) that provided the definitive
diagnosis within the past 42 days

- Enrollment on COG-D9902 required

- Patients must have a performance status corresponding to Eastern Cooperative Oncology
Group (ECOG) scores of 0, 1, or 2; use Karnofsky for patients > 16 years of age and
Lansky for patients =< 16 years of age

- Absolute neutrophil count (ANC) >= 750/μL

- Abnormal blood counts are permissible if there is bone marrow biopsy or aspirate
proven bone marrow involvement by RMS

- Platelet count >= 75,000/μL

- Abnormal blood counts are permissible if there is bone marrow biopsy or aspirate
proven bone marrow involvement by RMS

- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min OR
maximum serum creatinine based on age/gender as follows:

- 0.4 mg/dL (for patients 1 to 5 months of age)

- 0.5 mg/dL (for patients 6 to 11 months of age)

- 0.6 mg/dL (for patients 1 year of age)

- 0.8 mg/dL (for patients 2 to 5 years of age)

- 1.0 mg/dL (for patients 6 to 9 years of age)

- 1.2 mg/dL (for patients 10 to 12 years of age)

- 1.5 mg/dL (males) or 1.4 mg/dL (females) (for patients 13 to 15 years of age)

- 1.7 mg/dL (males) or 1.4 mg/dL (females) (for patients >= 16 years of age)

- Patients with urinary tract obstruction by tumor must meet the renal function
criteria listed above AND must have unimpeded urinary flow established via
decompression of the obstructed portion of the urinary tract

- Total bilirubin =< 1.5 times upper limit of normal (ULN) for age (unless there is
evidence of biliary obstruction by the tumor)

- Shortening fraction >=≥ 27% by echocardiogram (ECHO) OR ejection fraction >= 50% by
radionuclide angiogram

- Not pregnant or nursing

- Negative pregnancy test

- Sexually active patients of childbearing potential must agree to use effective
contraception during therapy (groups1 and 2) and for at least 3 months after the last
dose of cixutumumab (group 1)

- No uncontrolled infection

- No known type I or type II diabetes mellitus (for patients enrolled in group 1)

- No prior chemotherapy or radiotherapy except corticosteroids or emergent radiotherapy

- Patients requiring emergency radiation are eligible

- No concurrent growth hormone therapy

- All patients and/or their parents or legal guardians must sign a written informed

Type of Study:


Study Design:

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

Outcome Measure:

Incidence of adverse events assessed by Common Terminology Criteria for Adverse Events version 4.0

Outcome Time Frame:

6 months

Safety Issue:


Principal Investigator

Suman Malempati

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Oncology Group


United States: Food and Drug Administration

Study ID:




Start Date:

January 2010

Completion Date:

Related Keywords:

  • Adult Rhabdomyosarcoma
  • Alveolar Childhood Rhabdomyosarcoma
  • Embryonal Childhood Rhabdomyosarcoma
  • Metastatic Childhood Soft Tissue Sarcoma
  • Previously Untreated Childhood Rhabdomyosarcoma
  • Stage IV Adult Soft Tissue Sarcoma
  • Rhabdomyosarcoma
  • Rhabdomyosarcoma, Embryonal
  • Sarcoma



Baylor College of Medicine Houston, Texas  77030
Johns Hopkins University Baltimore, Maryland  21205
Cleveland Clinic Foundation Cleveland, Ohio  44195
Mayo Clinic Rochester, Minnesota  55905
Children's Hospital of Philadelphia Philadelphia, Pennsylvania  19104
University of Mississippi Medical Center Jackson, Mississippi  39216-4505
Washington University School of Medicine Saint Louis, Missouri  63110
Medical University of South Carolina Charleston, South Carolina  29425-0721
Rhode Island Hospital Providence, Rhode Island  02903
Midwest Children's Cancer Center Milwaukee, Wisconsin  53226
Sinai Hospital of Baltimore Baltimore, Maryland  21225
Bronson Methodist Hospital Kalamazoo, Michigan  49007
Loyola University Medical Center Maywood, Illinois  60153
Morristown Memorial Hospital Morristown, New Jersey  07962-1956
Newark Beth Israel Medical Center Newark, New Jersey  07112
Dana-Farber Cancer Institute Boston, Massachusetts  02115
University of Arkansas for Medical Sciences Little Rock, Arkansas  72205
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
Broward General Medical Center Fort Lauderdale, Florida  33316
All Children's Hospital St. Petersburg, Florida  33701
Saint Jude Midwest Affiliate Peoria, Illinois  61637
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
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
Overlook Hospital Summit, New Jersey  07902-0220
Cincinnati Children's Hospital Medical Center Cincinnati, Ohio  45229-3039
Primary Children's Medical Center Salt Lake City, Utah  84113-1100
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
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
Lee Memorial Health System Fort Myers, Florida  33902
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
Vanderbilt University Nashville, Tennessee  37232-6305
University of North Carolina Chapel Hill, North Carolina  27599
Duke University Medical Center Durham, North Carolina  27710
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 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
Oregon Health and Science University Portland, Oregon  97201
Tulane University Health Sciences Center New Orleans, Louisiana  70112
Virginia Commonwealth University Richmond, Virginia  
David Geffen School of Medicine at UCLA Los Angeles, California  90095
University of Chicago Comprehensive Cancer Center Chicago, Illinois  60637-1470
Seattle Children's Hospital Seattle, Washington  98105
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
University of Hawaii Honolulu, Hawaii  96813
Saint Luke's Mountain States Tumor Institute Boise, Idaho  83712
Kalamazoo Center for Medical Studies Kalamazoo, Michigan  49008
Saint John's Mercy Medical Center Saint Louis, Missouri  63141
Nevada Cancer Research Foundation CCOP Las Vegas, Nevada  89106
Columbia University Medical Center New York, New York  10032
State University of New York Upstate Medical University Syracuse, New York  13210
Natalie W Bryant Cancer Center Tulsa, Oklahoma  74136
Saint Vincent Hospital Green Bay, Wisconsin  54301
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
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
Walter Reed National Military Medical Center Bethesda, Maryland  20889
Riley Hospital for Children Indianapolis, Indiana  46202
Cardinal Glennon Children's Medical Center St. Louis, Missouri  63104
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
Saint Mary's Hospital West Palm Beach, Florida  33407
Saint Joseph's Regional Medical Center Paterson, New Jersey  07503
Childrens Hospital-King's Daughters Norfolk, Virginia  23507
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
Children's Hospital-Main Campus New Orleans, Louisiana  70118
Greenville Cancer Treatment Center Greenville, South Carolina  29605
Sanford USD Medical Center - Sioux Falls Sioux Falls, South Dakota  57117-5134
Providence Sacred Heart Medical Center and Children's Hospital Spokane, Washington  99204
Mattel Children's Hospital UCLA Los Angeles, California  90095