Cixutumumab in Treating Patients With Relapsed or Refractory Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00831844
First received: January 28, 2009
Last updated: March 18, 2015
Last verified: March 2015

January 28, 2009
March 18, 2015
January 2009
April 2013   (final data collection date for primary outcome measure)
Disease Response [ Time Frame: First six treatment cycles - 24 weeks ] [ Designated as safety issue: No ]
Response rates will be calculated as the percent of patients whose best response is a Complete Response (CR) or Partial Response (PR).
  • Response rate [ Designated as safety issue: No ]
  • Toxicity [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00831844 on ClinicalTrials.gov Archive Site
Not Provided
  • Relationship between tumor expression of IGF-I, IGF-II, and IGF-IR and response [ Designated as safety issue: No ]
  • Human anti-human antibody response [ Designated as safety issue: No ]
  • Effect of cixutumumab 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 [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Cixutumumab in Treating Patients With Relapsed or Refractory Solid Tumors
A Phase II Study of IMC-A12 (Anti-IGF-I Receptor Monoclonal Antibody, NSC #742460) in Children With Relapsed/Refractory Solid Tumors

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.

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.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • 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
    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 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.
    Interventions:
    • Biological: cixutumumab
    • Other: laboratory biomarker analysis
  • 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.
    Interventions:
    • Biological: cixutumumab
    • Other: laboratory biomarker analysis
  • 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.
    Interventions:
    • Biological: cixutumumab
    • Other: laboratory biomarker analysis
  • 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.
    Interventions:
    • Biological: cixutumumab
    • Other: laboratory biomarker analysis
  • 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.
    Interventions:
    • Biological: cixutumumab
    • Other: laboratory biomarker analysis
  • 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.
    Interventions:
    • Biological: cixutumumab
    • Other: laboratory biomarker analysis
  • 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.
    Interventions:
    • Biological: cixutumumab
    • Other: laboratory biomarker analysis
  • 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.
    Interventions:
    • Biological: cixutumumab
    • Other: laboratory biomarker analysis
  • 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.
    Interventions:
    • Biological: cixutumumab
    • Other: laboratory biomarker analysis
  • 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.
    Interventions:
    • Biological: cixutumumab
    • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
116
October 2013
April 2013   (final data collection date for primary outcome measure)

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
Both
7 Months to 30 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Canada
 
NCT00831844
NCI-2009-01170, NCI-2009-01170, CDR0000633186, COG-ADVL0821, ADVL0821, ADVL0821, U10CA098543
Yes
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Brenda Weigel, MD Children's Oncology Group
National Cancer Institute (NCI)
March 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP