Cixutumumab in Treating Patients With Relapsed or Refractory Solid Tumors
- Conditions
- Adult RhabdomyosarcomaAdult Synovial SarcomaRecurrent Adrenocortical CarcinomaRecurrent Childhood RhabdomyosarcomaRecurrent Adult Soft Tissue SarcomaRecurrent RetinoblastomaRecurrent Childhood Liver CancerRecurrent OsteosarcomaChildhood HepatoblastomaChildhood Synovial Sarcoma
- Interventions
- Biological: cixutumumabOther: laboratory biomarker analysis
- Registration Number
- NCT00831844
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
This phase II trial is studying the side effects and how well cixutumumab works in treating patients with relapsed or refractory solid tumors. Monoclonal antibodies, such as cixutumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them.
- Detailed Description
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 insulin-like growth factor (IGF)-I, IGF-II, and IGF-I receptor (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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 116
-
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 Central Nervous System (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 Eastern Cooperative Oncology Group (ECOG) PS 0-2
-
Absolute neutrophil count (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
-
Alanine transaminase (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
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Group 3 - Recurrent or Refractory Rhabdomyosarcoma laboratory biomarker analysis Group 3 - Recurrent or Refractory Rhabdomyosarcoma. Patients receive cixutumumab 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. Grp 4-Recurrent or Refractory Adrenocortical Carcinoma cixutumumab Group 4 - Recurrent or Refractory Adrenocortical Carcinoma. Patients receive cixutumumab 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. Grp 4-Recurrent or Refractory Adrenocortical Carcinoma laboratory biomarker analysis Group 4 - Recurrent or Refractory Adrenocortical Carcinoma. Patients receive cixutumumab 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. Grp 6 - Neuroblastoma-MIBG Positive Without Measurable Disease cixutumumab Group 6 - Recurrent or Refractory Neuroblastoma -meta-iodobenzylguanidine (MIBG) Positive Without Measurable Disease. Patients receive cixutumumab 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. Group 2 - Recurrent or Refractory Synovial Sarcoma laboratory biomarker analysis Group 2 - Recurrent or Refractory Synovial Sarcoma. Patients receive cixutumumab 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. Group 1 - Recurrent or Refractory Hepatoblastoma cixutumumab Group 1 - Recurrent or Refractory Hepatoblastoma. Patients receive cixutumumab 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. Grp 5-Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor cixutumumab Group 5 - Recurrent or Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor. Patients receive cixutumumab 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. Group 1 - Recurrent or Refractory Hepatoblastoma laboratory biomarker analysis Group 1 - Recurrent or Refractory Hepatoblastoma. Patients receive cixutumumab 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. Group 3 - Recurrent or Refractory Rhabdomyosarcoma cixutumumab Group 3 - Recurrent or Refractory Rhabdomyosarcoma. Patients receive cixutumumab 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. Group 2 - Recurrent or Refractory Synovial Sarcoma cixutumumab Group 2 - Recurrent or Refractory Synovial Sarcoma. Patients receive cixutumumab 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. Grp 5-Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor laboratory biomarker analysis Group 5 - Recurrent or Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor. Patients receive cixutumumab 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. Grp 6 - Neuroblastoma-MIBG Positive Without Measurable Disease laboratory biomarker analysis Group 6 - Recurrent or Refractory Neuroblastoma -meta-iodobenzylguanidine (MIBG) Positive Without Measurable Disease. Patients receive cixutumumab 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. Grp 7-Neuroblastoma with measurable disease laboratory biomarker analysis Group 7 - Recurrent or Refractory Neuroblastoma -With Measurable Disease. Patients receive cixutumumab 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. Grp 7-Neuroblastoma with measurable disease cixutumumab Group 7 - Recurrent or Refractory Neuroblastoma -With Measurable Disease. Patients receive cixutumumab 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. Group 10 - Recurrent or Refractory Retinoblastoma cixutumumab Group 10 - Recurrent or Refractory Retinoblastoma. Patients receive cixutumumab 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. Group 8 - Recurrent Osteosarcoma cixutumumab Group 8 - Recurrent Osteosarcoma. Patients receive cixutumumab 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. Group 9 - Recurrent or Refractory Wilms Tumor cixutumumab Group 9 - Recurrent or Refractory Wilms Tumor. Patients receive cixutumumab 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. Group 9 - Recurrent or Refractory Wilms Tumor laboratory biomarker analysis Group 9 - Recurrent or Refractory Wilms Tumor. Patients receive cixutumumab 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. Group 10 - Recurrent or Refractory Retinoblastoma laboratory biomarker analysis Group 10 - Recurrent or Refractory Retinoblastoma. Patients receive cixutumumab 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. Group 8 - Recurrent Osteosarcoma laboratory biomarker analysis Group 8 - Recurrent Osteosarcoma. Patients receive cixutumumab 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.
- Primary Outcome Measures
Name Time Method Disease Response First six treatment cycles - 24 weeks Response rates will be calculated as the percent of patients whose best response is a Complete Response (CR) or Partial Response (PR).
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (105)
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
University of Illinois
🇺🇸Chicago, Illinois, United States
Miami Children's Hospital
🇺🇸Miami, Florida, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
University of California San Francisco Medical Center-Parnassus
🇺🇸San Francisco, California, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
University of Kentucky
🇺🇸Lexington, Kentucky, United States
Sinai Hospital of Baltimore
🇺🇸Baltimore, Maryland, United States
Janeway Child Health Centre
🇨🇦Saint John's, Newfoundland and Labrador, Canada
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
Southern California Permanente Medical Group
🇺🇸Downey, California, United States
Miller Children's Hospital
🇺🇸Long Beach, California, United States
Children's Hospital Central California
🇺🇸Madera, California, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Kaiser Permanente-Oakland
🇺🇸Oakland, California, United States
Childrens Hospital of Orange County
🇺🇸Orange, California, United States
Lucile Packard Children's Hospital Stanford University
🇺🇸Palo Alto, California, United States
Connecticut Children's Medical Center
🇺🇸Hartford, Connecticut, United States
Alfred I duPont Hospital for Children
🇺🇸Wilmington, Delaware, United States
Lee Memorial Health System
🇺🇸Fort Myers, Florida, United States
Lombardi Comprehensive Cancer Center at Georgetown University
🇺🇸Washington, District of Columbia, United States
Nemours Children's Clinic - Jacksonville
🇺🇸Jacksonville, Florida, United States
UF Cancer Center at Orlando Health
🇺🇸Orlando, Florida, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
🇺🇸Miami, Florida, United States
Nemours Childrens Clinic - Orlando
🇺🇸Orlando, Florida, United States
Nemours Children's Clinic - Pensacola
🇺🇸Pensacola, Florida, United States
Children's Healthcare of Atlanta - Egleston
🇺🇸Atlanta, Georgia, United States
University of Hawaii
🇺🇸Honolulu, Hawaii, United States
Saint Luke's Mountain States Tumor Institute
🇺🇸Boise, Idaho, United States
Lurie Children's Hospital-Chicago
🇺🇸Chicago, Illinois, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
Southern Illinois University
🇺🇸Springfield, Illinois, United States
Saint Jude Midwest Affiliate
🇺🇸Peoria, Illinois, United States
Indiana University Medical Center
🇺🇸Indianapolis, Indiana, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Wayne State University/Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
University of Minnesota Medical Center-Fairview
🇺🇸Minneapolis, Minnesota, United States
Nevada Cancer Research Foundation CCOP
🇺🇸Las Vegas, Nevada, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
UMDNJ - Robert Wood Johnson University Hospital
🇺🇸New Brunswick, New Jersey, United States
University of New Mexico Cancer Center
🇺🇸Albuquerque, New Mexico, United States
Albany Medical Center
🇺🇸Albany, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
New York Medical College
🇺🇸Valhalla, New York, United States
State University of New York Upstate Medical University
🇺🇸Syracuse, New York, United States
Carolinas Medical Center
🇺🇸Charlotte, North Carolina, United States
Children's Hospital Medical Center of Akron
🇺🇸Akron, Ohio, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Rainbow Babies and Childrens Hospital
🇺🇸Cleveland, Ohio, United States
Penn State Hershey Children's Hospital
🇺🇸Hershey, Pennsylvania, United States
University of Missouri - Ellis Fischel
🇺🇸Columbia, Missouri, United States
Children's Hospital of Pittsburgh of UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
Palmetto Health Richland
🇺🇸Columbia, South Carolina, United States
Greenville Cancer Treatment Center
🇺🇸Greenville, South Carolina, United States
East Tennessee Childrens Hospital
🇺🇸Knoxville, Tennessee, United States
Texas Tech University Health Science Center-Amarillo
🇺🇸Amarillo, Texas, United States
Vanderbilt-Ingram Cancer Center
🇺🇸Nashville, Tennessee, United States
Medical City Dallas Hospital
🇺🇸Dallas, Texas, United States
Cook Children's Medical Center
🇺🇸Fort Worth, Texas, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Scott and White Memorial Hospital
🇺🇸Temple, Texas, United States
University of Texas Health Science Center at San Antonio
🇺🇸San Antonio, Texas, United States
Primary Children's Hospital
🇺🇸Salt Lake City, Utah, United States
Childrens Hospital-King's Daughters
🇺🇸Norfolk, Virginia, United States
Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States
Seattle Children's Hospital
🇺🇸Seattle, Washington, United States
Providence Sacred Heart Medical Center and Children's Hospital
🇺🇸Spokane, Washington, United States
The Children's Hospital at Westmead
🇦🇺Westmead, New South Wales, Australia
Royal Brisbane and Women's Hospital
🇦🇺Herston, Queensland, Australia
Royal Children's Hospital
🇦🇺Parkville, Victoria, Australia
Princess Margaret Hospital for Children
🇦🇺Perth, Western Australia, Australia
British Columbia Children's Hospital
🇨🇦Vancouver, British Columbia, Canada
CancerCare Manitoba
🇨🇦Winnipeg, Manitoba, Canada
IWK Health Centre
🇨🇦Halifax, Nova Scotia, Canada
Centre Hospitalier Universitaire Sainte-Justine
🇨🇦Montreal, Quebec, Canada
Hospital for Sick Children
🇨🇦Toronto, Ontario, Canada
Allan Blair Cancer Centre
🇨🇦Regina, Saskatchewan, Canada
Saskatoon Cancer Centre
🇨🇦Saskatoon, Saskatchewan, Canada
Saint Joseph Children's Hospital of Tampa
🇺🇸Tampa, Florida, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Midwest Children's Cancer Center
🇺🇸Milwaukee, Wisconsin, United States
Children's Hospital and Medical Center of Omaha
🇺🇸Omaha, Nebraska, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
T C Thompson Children's Hospital
🇺🇸Chattanooga, Tennessee, United States
New York University Langone Medical Center
🇺🇸New York, New York, United States
Children's Hospitals and Clinics of Minnesota - Minneapolis
🇺🇸Minneapolis, Minnesota, United States
Saint John Hospital and Medical Center
🇺🇸Detroit, Michigan, United States
All Children's Hospital
🇺🇸Saint Petersburg, Florida, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
University of Mississippi Medical Center
🇺🇸Jackson, Mississippi, United States
Mary Bridge Children's Hospital and Health Center
🇺🇸Tacoma, Washington, United States
The Childrens Mercy Hospital
🇺🇸Kansas City, Missouri, United States
University of Rochester
🇺🇸Rochester, New York, United States
Saint Mary's Hospital
🇺🇸West Palm Beach, Florida, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Newark Beth Israel Medical Center
🇺🇸Newark, New Jersey, United States
Helen DeVos Children's Hospital at Spectrum Health
🇺🇸Grand Rapids, Michigan, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Lehigh Valley Hospital - Muhlenberg
🇺🇸Bethlehem, Pennsylvania, United States
Florida Hospital
🇺🇸Orlando, Florida, United States
C S Mott Children's Hospital
🇺🇸Ann Arbor, Michigan, United States