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A Phase II Study of IMC-A12 (Anti-IGF-I Receptor Monoclonal Antibody, IND #100947, NSC #742460) in Children With Relapsed/Refractory Solid Tumors

Phase 2
7 Months
30 Years
Open (Enrolling)
Adult Rhabdomyosarcoma, Adult Synovial Sarcoma, Childhood Hepatoblastoma, Childhood Synovial Sarcoma, Previously Treated Childhood Rhabdomyosarcoma, Recurrent Adrenocortical Carcinoma, Recurrent Adult Soft Tissue Sarcoma, Recurrent Childhood Liver Cancer, Recurrent Childhood Rhabdomyosarcoma, Recurrent Childhood Soft Tissue Sarcoma, Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor, Recurrent Neuroblastoma, Recurrent Osteosarcoma, Recurrent Retinoblastoma, Recurrent Wilms Tumor and Other Childhood Kidney Tumors

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Trial Information

A Phase II Study of IMC-A12 (Anti-IGF-I Receptor Monoclonal Antibody, IND #100947, NSC #742460) in Children With Relapsed/Refractory Solid Tumors


I. To determine the response rate to IMC-A12 (cixutumumab) administered in various strata of
recurrent/refractory malignant solid tumors in childhood and young adulthood.

II. To further define and describe the toxicities of IMC-A12. III. To further characterize
the pharmacokinetics of IMC-A12.


I. To examine the relationship between tumor expression of IGF-I, IGF-II, and IGF-IR and
response to IMC-A12.

II. To determine the human anti-human antibody (HAHA) response after treatment with IMC-A12.

III. To further evaluate the effect of IMC-A12 on circulating levels of proteins involved in
linear growth and glucose homeostasis, including IGF-I, IGF-II, IGF-BP3, growth hormone,
insulin, and C-peptide.

OUTLINE: This is a multicenter study. Patients are stratified according to disease type.

Patients receive cixutumumab intravenously (IV) over 1 hour on days 1, 8, 15, and 22.
Treatment repeats every 28 days for up to 24 courses in the absence of disease progression
or unacceptable toxicity.

Patients undergo blood sample collection periodically for correlative laboratory studies.
Samples are analyzed for IGF-I, IGF-II, IGF-BP3, growth hormone, insulin, and C-peptide
levels and for immunogenicity.

Inclusion Criteria:

- Histologically confirmed malignant solid tumor, including the following:

- Osteosarcoma

- Ewing sarcoma/peripheral primitive neuroectodermal tumor

- Rhabdomyosarcoma

- Neuroblastoma

- Wilms tumor

- Synovial sarcoma

- Hepatoblastoma

- Adrenocortical carcinoma

- Retinoblastoma

- No known curative therapy or therapy proven to prolong survival with an acceptable
quality of life exists

- Radiographically measurable disease*, defined as ≥ 1 unidimensionally measurable
lesion ≥ 20 mm by MRI or CT scan or ≥ 10 mm by spiral CT scan

- The following are not considered measurable disease:

- Ascites, pleural effusions, or other malignant fluid collections

- Bone marrow infiltration by tumor

- Lesions detected only by non-MIBG nuclear medicine studies (e.g., bone

- Previously irradiated lesions that have not demonstrated clear progression

- No known CNS metastases unless they were treated by surgery or radiotherapy AND are
stable with no recurrent lesions for ≥ 3 months

- Lansky or Karnofsky performance status (PS) 50-100% OR ECOG PS 0-2

- ANC ≥ 1,000/mm³ (> 250/mm³ for patients with neuroblastoma)

- Platelet count ≥ 75,000/mm³ (> 25,000/mm³ for patients with neuroblastoma)
(transfusion independent)

- Hemoglobin ≥ 8.0 g/dL (≥ 7.5 g/dL for patients with neuroblastoma) (RBC transfusion

- Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR serum
creatinine normal 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 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)

- Total bilirubin ≤ 1.5 times upper limit of normal for age

- ALT ≤ 110 U/L

- Serum albumin ≥ 2 g/dL

- Blood glucose normal

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 3 months after
completion of study treatment

- Able to comply with safety monitoring requirements of study

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to study drug

- No uncontrolled infection

- No known type I or II diabetes mellitus

- Recovered from prior chemotherapy, immunotherapy, or radiotherapy

- More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for

- At least 7 days since prior hematopoietic growth factors (14 days for pegfilgrastim)

- At least 6 weeks since prior monoclonal antibody therapy

- At least 7 days since other prior antineoplastic biologic agents

- No prior monoclonal antibody targeting the IGF-IR

- No prior small molecule kinase inhibitors of IGF-IR

- At least 2 weeks since prior local palliative (small port) radiotherapy

- At least 3 months since prior total-body irradiation, craniospinal radiotherapy, or
radiotherapy to ≥ 50% of the pelvis

- At least 6 weeks since other prior substantial bone marrow radiotherapy

- At least 2 months since prior stem cell transplantation

- No evidence of graft-versus-host disease

- Concurrent corticosteroids allowed provided dose is stable or decreasing over the
past 7 days

- Intermittent use of corticosteroids to manage infusional reactions allowed

- No other concurrent anticancer therapy, including chemotherapy, radiotherapy,
immunotherapy, or biologic therapy

- No other concurrent investigational agents

- No concurrent insulin or growth hormone therapy

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response rate

Outcome Description:

Response rates will be calculated as the percent of patients whose best response is a CR or PR, and the 95% confidence intervals will be constructed according to the method of Chang.

Outcome Time Frame:

24 weeks

Safety Issue:


Principal Investigator

Brenda Weigel

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Oncology Group


United States: Food and Drug Administration

Study ID:




Start Date:

January 2009

Completion Date:

Related Keywords:

  • Adult Rhabdomyosarcoma
  • Adult Synovial Sarcoma
  • Childhood Hepatoblastoma
  • Childhood Synovial Sarcoma
  • Previously Treated Childhood Rhabdomyosarcoma
  • Recurrent Adrenocortical Carcinoma
  • Recurrent Adult Soft Tissue Sarcoma
  • Recurrent Childhood Liver Cancer
  • Recurrent Childhood Rhabdomyosarcoma
  • Recurrent Childhood Soft Tissue Sarcoma
  • Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
  • Recurrent Neuroblastoma
  • Recurrent Osteosarcoma
  • Recurrent Retinoblastoma
  • Recurrent Wilms Tumor and Other Childhood Kidney Tumors
  • Carcinoma
  • Kidney Neoplasms
  • Liver Neoplasms
  • Wilms Tumor
  • Neuroblastoma
  • Osteosarcoma
  • Retinoblastoma
  • Rhabdomyosarcoma
  • Sarcoma, Synovial
  • Neuroectodermal Tumors
  • Neuroectodermal Tumors, Primitive
  • Hepatoblastoma
  • Adrenocortical Carcinoma
  • Rhabdomyosarcoma, Embryonal
  • Sarcoma
  • Sarcoma, Ewing's
  • Neuroectodermal Tumors, Primitive, Peripheral



Baylor College of Medicine Houston, Texas  77030
Memorial Sloan Kettering Cancer Center New York, New York  10021
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 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
Loyola University Medical Center Maywood, Illinois  60153
Newark Beth Israel Medical Center Newark, New Jersey  07112
New York Medical College Valhalla, New York  10595
Dana-Farber Cancer Institute Boston, Massachusetts  02115
University of Arkansas for Medical Sciences Little Rock, Arkansas  72205
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
Miami Children's Hospital Miami, Florida  33155-4069
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
Scott and White Memorial Hospital Temple, Texas  76508
Southern California Permanente Medical Group Downey, California  90242
Children's Hospital Central California Madera, California  93638-8762
Children's Hospital Medical Center of Akron Akron, Ohio  44308
Cincinnati Children's Hospital Medical Center Cincinnati, Ohio  45229-3039
Primary Children's Medical Center Salt Lake City, Utah  84113-1100
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
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
Connecticut Children's Medical Center Hartford, Connecticut  06106
Vanderbilt University Nashville, Tennessee  37232-6305
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
Wayne State University Detroit, Michigan  48202
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
Virginia Commonwealth University Richmond, Virginia  
Florida Hospital Orlando, Florida  32803
University of Chicago Comprehensive Cancer Center Chicago, Illinois  60637-1470
Seattle Children's Hospital Seattle, Washington  98105
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 John Hospital and Medical Center Detroit, Michigan  48236
Nevada Cancer Research Foundation CCOP Las Vegas, Nevada  89106
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
University of Illinois Chicago, Illinois  60612
Cook Children's Medical Center Fort Worth, Texas  76104
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
UMDNJ - Robert Wood Johnson University Hospital New Brunswick, New Jersey  08903
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
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
Children's Hospital and Medical Center of Omaha Omaha, Nebraska  68114
Texas Tech University Health Science Center-Amarillo Amarillo, Texas  79106
Childrens Hospital-King's Daughters Norfolk, Virginia  23507
Lucile Packard Children's Hospital Stanford University Palo Alto, California  94304
University of California San Francisco Medical Center-Parnassus San Francisco, California  94143
Greenville Cancer Treatment Center Greenville, South Carolina  29605
T C Thompson Children's Hospital Chattanooga, Tennessee  37403
Providence Sacred Heart Medical Center and Children's Hospital Spokane, Washington  99204