Cixutumumab in Treating Patients With Relapsed or Refractory Solid Tumors
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ClinicalTrials.gov Identifier: NCT00831844 |
Recruitment Status :
Completed
First Posted : January 29, 2009
Results First Posted : March 30, 2015
Last Update Posted : March 30, 2015
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
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 | Biological: cixutumumab Other: laboratory biomarker analysis | Phase 2 |
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.
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 116 participants |
Allocation: | Non-Randomized |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase II Study of IMC-A12 (Anti-IGF-I Receptor Monoclonal Antibody, NSC #742460) in Children With Relapsed/Refractory Solid Tumors |
Study Start Date : | January 2009 |
Actual Primary Completion Date : | April 2013 |
Actual Study Completion Date : | October 2013 |

Arm | Intervention/treatment |
---|---|
Experimental: Group 1 - Recurrent or Refractory Hepatoblastoma
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.
|
Biological: cixutumumab
Given IV: Week 1 day 1, 9 mg/kg/dose over 1 hour. Week 2 Day 8, 9 mg/kg/dose over 1 hour. Week 3 Day 15, 9 mg/kg/dose over 1 hour. Week 4 Day 22, 9 mg/kg/dose over 1 hour.
Other Names:
Other: laboratory biomarker analysis Correlative studies |
Experimental: Group 2 - Recurrent or Refractory Synovial Sarcoma
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.
|
Biological: cixutumumab
Given IV: Week 1 day 1, 9 mg/kg/dose over 1 hour. Week 2 Day 8, 9 mg/kg/dose over 1 hour. Week 3 Day 15, 9 mg/kg/dose over 1 hour. Week 4 Day 22, 9 mg/kg/dose over 1 hour.
Other Names:
Other: laboratory biomarker analysis Correlative studies |
Experimental: Group 3 - Recurrent or Refractory Rhabdomyosarcoma
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.
|
Biological: cixutumumab
Given IV: Week 1 day 1, 9 mg/kg/dose over 1 hour. Week 2 Day 8, 9 mg/kg/dose over 1 hour. Week 3 Day 15, 9 mg/kg/dose over 1 hour. Week 4 Day 22, 9 mg/kg/dose over 1 hour.
Other Names:
Other: laboratory biomarker analysis Correlative studies |
Experimental: Grp 4-Recurrent or Refractory Adrenocortical Carcinoma
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.
|
Biological: cixutumumab
Given IV: Week 1 day 1, 9 mg/kg/dose over 1 hour. Week 2 Day 8, 9 mg/kg/dose over 1 hour. Week 3 Day 15, 9 mg/kg/dose over 1 hour. Week 4 Day 22, 9 mg/kg/dose over 1 hour.
Other Names:
Other: laboratory biomarker analysis Correlative studies |
Experimental: Grp 5-Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor
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.
|
Biological: cixutumumab
Given IV: Week 1 day 1, 9 mg/kg/dose over 1 hour. Week 2 Day 8, 9 mg/kg/dose over 1 hour. Week 3 Day 15, 9 mg/kg/dose over 1 hour. Week 4 Day 22, 9 mg/kg/dose over 1 hour.
Other Names:
Other: laboratory biomarker analysis Correlative studies |
Experimental: Grp 6 - Neuroblastoma-MIBG Positive Without Measurable Disease
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.
|
Biological: cixutumumab
Given IV: Week 1 day 1, 9 mg/kg/dose over 1 hour. Week 2 Day 8, 9 mg/kg/dose over 1 hour. Week 3 Day 15, 9 mg/kg/dose over 1 hour. Week 4 Day 22, 9 mg/kg/dose over 1 hour.
Other Names:
Other: laboratory biomarker analysis Correlative studies |
Experimental: Grp 7-Neuroblastoma with measurable disease
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.
|
Biological: cixutumumab
Given IV: Week 1 day 1, 9 mg/kg/dose over 1 hour. Week 2 Day 8, 9 mg/kg/dose over 1 hour. Week 3 Day 15, 9 mg/kg/dose over 1 hour. Week 4 Day 22, 9 mg/kg/dose over 1 hour.
Other Names:
Other: laboratory biomarker analysis Correlative studies |
Experimental: Group 8 - Recurrent Osteosarcoma
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.
|
Biological: cixutumumab
Given IV: Week 1 day 1, 9 mg/kg/dose over 1 hour. Week 2 Day 8, 9 mg/kg/dose over 1 hour. Week 3 Day 15, 9 mg/kg/dose over 1 hour. Week 4 Day 22, 9 mg/kg/dose over 1 hour.
Other Names:
Other: laboratory biomarker analysis Correlative studies |
Experimental: Group 9 - Recurrent or Refractory Wilms Tumor
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.
|
Biological: cixutumumab
Given IV: Week 1 day 1, 9 mg/kg/dose over 1 hour. Week 2 Day 8, 9 mg/kg/dose over 1 hour. Week 3 Day 15, 9 mg/kg/dose over 1 hour. Week 4 Day 22, 9 mg/kg/dose over 1 hour.
Other Names:
Other: laboratory biomarker analysis Correlative studies |
Experimental: Group 10 - Recurrent or Refractory Retinoblastoma
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.
|
Biological: cixutumumab
Given IV: Week 1 day 1, 9 mg/kg/dose over 1 hour. Week 2 Day 8, 9 mg/kg/dose over 1 hour. Week 3 Day 15, 9 mg/kg/dose over 1 hour. Week 4 Day 22, 9 mg/kg/dose over 1 hour.
Other Names:
Other: laboratory biomarker analysis Correlative studies |
- Disease Response [ Time Frame: 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).

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Ages Eligible for Study: | 7 Months to 30 Years (Child, Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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
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Radiographically measurable disease*, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by MRI or CT scan or ≥ 10 mm by spiral CT scan
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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
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- 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)
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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
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At least 2 months since prior stem cell transplantation
- No evidence of graft-versus-host disease
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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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00831844

Principal Investigator: | Brenda Weigel, MD | Children's Oncology Group |
Responsible Party: | National Cancer Institute (NCI) |
ClinicalTrials.gov Identifier: | NCT00831844 |
Other Study ID Numbers: |
NCI-2009-01170 NCI-2009-01170 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) CDR0000633186 ( Other Identifier: Clinical Trials.gov ) COG-ADVL0821 ( Other Identifier: Children's Oncology Group ) ADVL0821 ( Other Identifier: Children's Oncology Group ) ADVL0821 ( Other Identifier: CTEP ) U10CA098543 ( U.S. NIH Grant/Contract ) |
First Posted: | January 29, 2009 Key Record Dates |
Results First Posted: | March 30, 2015 |
Last Update Posted: | March 30, 2015 |
Last Verified: | March 2015 |
Neoplasms Sarcoma Neuroblastoma Osteosarcoma Rhabdomyosarcoma Sarcoma, Ewing Neuroectodermal Tumors Neuroectodermal Tumors, Primitive Wilms Tumor Retinoblastoma Rhabdomyosarcoma, Embryonal Sarcoma, Synovial Adrenocortical Carcinoma Hepatoblastoma Neoplasms, Connective and Soft Tissue |
Neoplasms by Histologic Type Neuroectodermal Tumors, Primitive, Peripheral Neoplasms, Neuroepithelial Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplasms by Site Neoplasms, Bone Tissue Neoplasms, Connective Tissue Myosarcoma Neoplasms, Muscle Tissue Neoplasms, Complex and Mixed Kidney Neoplasms Urologic Neoplasms Urogenital Neoplasms |