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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
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Description
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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.

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

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.


Study Design
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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

Resource links provided by the National Library of Medicine


Arms and Interventions
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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:
  • anti-IGF-1R recombinant monoclonal antibody IMC-A12
  • IMC-A12

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:
  • anti-IGF-1R recombinant monoclonal antibody IMC-A12
  • IMC-A12

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:
  • anti-IGF-1R recombinant monoclonal antibody IMC-A12
  • IMC-A12

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:
  • anti-IGF-1R recombinant monoclonal antibody IMC-A12
  • IMC-A12

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:
  • anti-IGF-1R recombinant monoclonal antibody IMC-A12
  • IMC-A12

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:
  • anti-IGF-1R recombinant monoclonal antibody IMC-A12
  • IMC-A12

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:
  • anti-IGF-1R recombinant monoclonal antibody IMC-A12
  • IMC-A12

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:
  • anti-IGF-1R recombinant monoclonal antibody IMC-A12
  • IMC-A12

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:
  • anti-IGF-1R recombinant monoclonal antibody IMC-A12
  • IMC-A12

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:
  • anti-IGF-1R recombinant monoclonal antibody IMC-A12
  • IMC-A12

Other: laboratory biomarker analysis
Correlative studies


Outcome Measures
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Primary Outcome Measures :
  1. 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).


Eligibility Criteria
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Ages Eligible for Study:   7 Months to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 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
Contacts and Locations
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Information from the National Library of Medicine

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


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Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Brenda Weigel, MD Children's Oncology Group
More Information
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00831844     History of Changes
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

Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms
Sarcoma
Neuroblastoma
Liver Neoplasms
Osteosarcoma
Rhabdomyosarcoma
Sarcoma, Ewing
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Wilms Tumor
Rhabdomyosarcoma, Embryonal
Retinoblastoma
Sarcoma, Synovial
Adrenocortical Carcinoma
Kidney Neoplasms
 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
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Myosarcoma