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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



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Children's Hospital of PhiladelphiaPhiladelphia, Pennsylvania  19104
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Washington University School of MedicineSaint Louis, Missouri  63110
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All Children's HospitalSt. Petersburg, Florida  33701
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Driscoll Children's HospitalCorpus Christi, Texas  78466
Southern California Permanente Medical GroupDowney, California  90242
Children's Hospital Central CaliforniaMadera, California  93638-8762
Kosair Children's HospitalLouisville, Kentucky  40202-3830
Children's Hospital Medical Center of AkronAkron, Ohio  44308
Overlook HospitalSummit, New Jersey  07902-0220
Cincinnati Children's Hospital Medical CenterCincinnati, Ohio  45229-3039
Primary Children's Medical CenterSalt Lake City, Utah  84113-1100
Rady Children's Hospital - San DiegoSan Diego, California  92123-4282
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Children's Hospital of Pittsburgh of UPMCPittsburgh, Pennsylvania  15213
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Lehigh Valley Hospital - MuhlenbergBethlehem, Pennsylvania  18017
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Connecticut Children's Medical CenterHartford, Connecticut  06106
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Duke University Medical CenterDurham, North Carolina  27710
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Yale UniversityNew Haven, Connecticut  06520
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Seattle Children's HospitalSeattle, Washington  98105
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Saint John's Mercy Medical CenterSaint Louis, Missouri  63141
Nevada Cancer Research Foundation CCOPLas Vegas, Nevada  89106
Columbia University Medical CenterNew York, New York  10032
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Natalie W Bryant Cancer CenterTulsa, Oklahoma  74136
Saint Vincent HospitalGreen Bay, Wisconsin  54301
Cook Children's Medical CenterFort Worth, Texas  76104
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West Virginia University CharlestonCharleston, West Virginia  25304
The Children's Medical Center of DaytonDayton, Ohio  45404
University of Minnesota Medical Center-FairviewMinneapolis, Minnesota  55455
C S Mott Children's HospitalAnn Arbor, Michigan  48109
Southern Illinois UniversitySpringfield, Illinois  62702
Walter Reed National Military Medical CenterBethesda, Maryland  20889
Riley Hospital for ChildrenIndianapolis, Indiana  46202
Cardinal Glennon Children's Medical CenterSt. Louis, Missouri  63104
UMDNJ - Robert Wood Johnson University HospitalNew Brunswick, New Jersey  08903
Phoenix Childrens HospitalPhoenix, Arizona  85016
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Alfred I duPont Hospital for ChildrenWilmington, Delaware  19803
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Saint Joseph Children's Hospital of TampaTampa, Florida  33607
Children's Healthcare of Atlanta - EglestonAtlanta, Georgia  30322
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Rainbow Babies and Childrens HospitalCleveland, Ohio  44106
Penn State Hershey Children's HospitalHershey, Pennsylvania  17033
Palmetto Health RichlandColumbia, South Carolina  29203
East Tennessee Childrens HospitalKnoxville, Tennessee  37916
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Children's Hospital ColoradoAurora, Colorado  80045
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