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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)
Both
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

Thank you

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


PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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
scan)

- Previously irradiated lesions that have not demonstrated clear progression
post-radiotherapy

- 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
allowed)

- 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
nitrosoureas)

- 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:

Interventional

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:

No

Principal Investigator

Brenda Weigel

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-01170

NCT ID:

NCT00831844

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

Name

Location

Baylor College of MedicineHouston, Texas  77030
Memorial Sloan Kettering Cancer CenterNew York, New York  10021
Cleveland Clinic FoundationCleveland, Ohio  44195
Mayo ClinicRochester, Minnesota  55905
Children's Hospital of PhiladelphiaPhiladelphia, Pennsylvania  19104
University of Mississippi Medical CenterJackson, Mississippi  39216-4505
Washington University School of MedicineSaint Louis, Missouri  63110
Medical City Dallas HospitalDallas, Texas  75230
University of Texas Health Science Center at San AntonioSan Antonio, Texas  78284-7811
Midwest Children's Cancer CenterMilwaukee, Wisconsin  53226
Sinai Hospital of BaltimoreBaltimore, Maryland  21225
Loyola University Medical CenterMaywood, Illinois  60153
Newark Beth Israel Medical CenterNewark, New Jersey  07112
New York Medical CollegeValhalla, New York  10595
Dana-Farber Cancer InstituteBoston, Massachusetts  02115
University of Arkansas for Medical SciencesLittle Rock, Arkansas  72205
University of Nebraska Medical CenterOmaha, Nebraska  68198-3330
Hackensack University Medical CenterHackensack, New Jersey  07601
Children's Hospital Los AngelesLos Angeles, California  90027-0700
Miami Children's HospitalMiami, Florida  33155-4069
All Children's HospitalSt. Petersburg, Florida  33701
Saint Jude Midwest AffiliatePeoria, Illinois  61637
Carolinas Medical CenterCharlotte, North Carolina  28232-2861
University of Oklahoma Health Sciences CenterOklahoma City, Oklahoma  73104
Scott and White Memorial HospitalTemple, Texas  76508
Southern California Permanente Medical GroupDowney, California  90242
Children's Hospital Central CaliforniaMadera, California  93638-8762
Children's Hospital Medical Center of AkronAkron, Ohio  44308
Cincinnati Children's Hospital Medical CenterCincinnati, Ohio  45229-3039
Primary Children's Medical CenterSalt Lake City, Utah  84113-1100
Children's Hospitals and Clinics of Minnesota - MinneapolisMinneapolis, Minnesota  55404
University of New Mexico Cancer CenterAlbuquerque, New Mexico  87131-5636
Nationwide Children's HospitalColumbus, Ohio  43205-2696
Children's Hospital of Pittsburgh of UPMCPittsburgh, Pennsylvania  15213
Mary Bridge Children's Hospital and Health CenterTacoma, Washington  98415-0299
Lehigh Valley Hospital - MuhlenbergBethlehem, Pennsylvania  18017
Lee Memorial Health SystemFort Myers, Florida  33902
University of Alabama at BirminghamBirmingham, Alabama  35294-3300
Connecticut Children's Medical CenterHartford, Connecticut  06106
Vanderbilt UniversityNashville, Tennessee  37232-6305
University of RochesterRochester, New York  14642
Nemours Children's Clinic - PensacolaPensacola, Florida  32504
Helen DeVos Children's Hospital at Spectrum HealthGrand Rapids, Michigan  49503
Wayne State UniversityDetroit, Michigan  48202
Albany Medical CenterAlbany, New York  12208
University of Texas Southwestern Medical CenterDallas, Texas  
University of KentuckyLexington, Kentucky  40536-0098
Oregon Health and Science UniversityPortland, Oregon  97201
Virginia Commonwealth UniversityRichmond, Virginia  
Florida HospitalOrlando, Florida  32803
University of Chicago Comprehensive Cancer CenterChicago, Illinois  60637-1470
Seattle Children's HospitalSeattle, Washington  98105
Childrens Memorial HospitalChicago, Illinois  60614
Kaiser Permanente-OaklandOakland, California  94611
Lombardi Comprehensive Cancer Center at Georgetown UniversityWashington, District of Columbia  20057
M D Anderson Cancer Center- OrlandoOrlando, Florida  32806
University of HawaiiHonolulu, Hawaii  96813
Saint Luke's Mountain States Tumor InstituteBoise, Idaho  83712
Saint John Hospital and Medical CenterDetroit, Michigan  48236
Nevada Cancer Research Foundation CCOPLas Vegas, Nevada  89106
New York University Langone Medical CenterNew York, New York  10016
Columbia University Medical CenterNew York, New York  10032
State University of New York Upstate Medical UniversitySyracuse, New York  13210
University of IllinoisChicago, Illinois  60612
Cook Children's Medical CenterFort Worth, Texas  76104
University of Miami Miller School of Medicine-Sylvester Cancer CenterMiami, Florida  33136
University of Minnesota Medical Center-FairviewMinneapolis, Minnesota  55455
C S Mott Children's HospitalAnn Arbor, Michigan  48109
Southern Illinois UniversitySpringfield, Illinois  62702
University Of Missouri-ColumbiaColumbia, Missouri  65212
UMDNJ - Robert Wood Johnson University HospitalNew Brunswick, New Jersey  08903
Miller Children's HospitalLong Beach, California  90806
Childrens Hospital of Orange CountyOrange, California  92868-3874
Alfred I duPont Hospital for ChildrenWilmington, Delaware  19803
Nemours Children's Clinic - JacksonvilleJacksonville, Florida  32207-8426
Nemours Childrens Clinic - OrlandoOrlando, Florida  32806
Saint Joseph Children's Hospital of TampaTampa, Florida  33607
Children's Healthcare of Atlanta - EglestonAtlanta, Georgia  30322
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
Saint Mary's HospitalWest Palm Beach, Florida  33407
Children's Hospital and Medical Center of OmahaOmaha, Nebraska  68114
Texas Tech University Health Science Center-AmarilloAmarillo, Texas  79106
Childrens Hospital-King's DaughtersNorfolk, Virginia  23507
Lucile Packard Children's Hospital Stanford UniversityPalo Alto, California  94304
University of California San Francisco Medical Center-ParnassusSan Francisco, California  94143
Greenville Cancer Treatment CenterGreenville, South Carolina  29605
T C Thompson Children's HospitalChattanooga, Tennessee  37403
Providence Sacred Heart Medical Center and Children's HospitalSpokane, Washington  99204