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Cixutumumab in Treating Patients With Relapsed or Refractory Solid Tumors
This study is currently recruiting participants.
Verified April 2011 by National Cancer Institute (NCI)

First Received on January 28, 2009.   Last Updated on April 2, 2011   History of Changes
Sponsor: Children's Oncology Group
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00831844
  Purpose

RATIONALE: 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.

PURPOSE: This phase II trial is studying the side effects and how well cixutumumab works in treating patients with relapsed or refractory solid tumors.


Condition Intervention Phase
Adrenocortical Carcinoma
Kidney Cancer
Liver Cancer
Neuroblastoma
Retinoblastoma
Sarcoma
Biological: cixutumumab
Other: laboratory biomarker analysis
Phase II

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of IMC-A12 (Anti-IGF-I Receptor Monoclonal Antibody, IND #100947, NSC #742460) in Children With Relapsed/Refractory Solid Tumors

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Response rate [ Designated as safety issue: No ]
  • Toxicity [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 140
Study Start Date: January 2009
Estimated Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • To determine the response rate in patients with relapsed or refractory malignant solid tumors treated with cixutumumab.
  • To further define and describe the toxicities of this drug in these patients.

Secondary

  • To examine the relationship between tumor expression of IGF-I, IGF-II, and IGF-IR and response in patients treated with this drug.
  • To determine the human anti-human antibody response in these patients after treatment with this drug.
  • To further evaluate the effect of this drug 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 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.

  Eligibility

Ages Eligible for Study:   up to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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 NOTE: *Measurable disease is not required for patients with neuroblastoma; patients with MIBG+ evaluable neuroblastoma are eligible
  • No known CNS metastases unless they were treated by surgery or radiotherapy AND are stable with no recurrent lesions for ≥ 3 months

PATIENT CHARACTERISTICS:

  • 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

PRIOR CONCURRENT THERAPY:

  • 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00831844

  Show 109 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Brenda Weigel, MD Masonic Cancer Center, University of Minnesota
  More Information

Additional Information:
No publications provided

Responsible Party: Gregory H. Reaman, Children's Oncology Group - Group Chair Office
ClinicalTrials.gov Identifier: NCT00831844     History of Changes
Other Study ID Numbers: CDR0000633186, COG-ADVL0821
Study First Received: January 28, 2009
Last Updated: April 2, 2011
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
recurrent osteosarcoma
recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor
adult rhabdomyosarcoma
previously treated childhood rhabdomyosarcoma
recurrent childhood rhabdomyosarcoma
recurrent adult soft tissue sarcoma
recurrent childhood soft tissue sarcoma
adult synovial sarcoma
childhood synovial sarcoma
recurrent adrenocortical carcinoma
recurrent neuroblastoma
recurrent Wilms tumor and other childhood kidney tumors
childhood hepatoblastoma
recurrent childhood liver cancer
recurrent retinoblastoma

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Kidney Neoplasms
Liver Neoplasms
Neuroblastoma
Retinoblastoma
Adrenocortical Carcinoma
Sarcoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Digestive System Neoplasms
Digestive System Diseases
Liver Diseases
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Retinal Neoplasms
Eye Neoplasms
Eye Diseases
Retinal Diseases

ClinicalTrials.gov processed this record on February 02, 2012