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: June 18, 2014
Last verified: June 2014
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Response rate [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Response rates will be calculated as the percent of patients whose best response is a CR or PR, and the 95% confidence intervals will be constructed according to the method of Chang.

  • Toxicity, graded according to NCI CTCAE version 4.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    Toxicity information recorded will include the type, severity, time of onset, time of resolution, and the probable association with the study regimen. Tables will be constructed to summarize the observed incidence by severity and type of toxicity.


Enrollment: 114
Study Start Date: January 2009
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (cixutumumab)
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
Other Names:
  • anti-IGF-1R recombinant monoclonal antibody IMC-A12
  • IMC-A12
Other: laboratory biomarker analysis
Correlative studies

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 IGF-I, IGF-II, and IGF-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.

  Eligibility

Ages Eligible for Study:   7 Months to 30 Years
Genders Eligible for Study:   Both
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 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 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
  • 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

  Show 105 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Brenda Weigel Children's Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00831844     History of Changes
Other Study ID Numbers: NCI-2009-01170, NCI-2009-01170, CDR0000633186, COG-ADVL0821, ADVL0821, ADVL0821, U10CA098543
Study First Received: January 28, 2009
Last Updated: June 18, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Kidney Neoplasms
Liver Neoplasms
Wilms Tumor
Neuroblastoma
Osteosarcoma
Retinoblastoma
Rhabdomyosarcoma
Sarcoma, Synovial
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Hepatoblastoma
Adrenocortical Carcinoma
Rhabdomyosarcoma, Embryonal
Sarcoma
Sarcoma, Ewing
Neuroectodermal Tumors, Primitive, Peripheral
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Digestive System Neoplasms
Digestive System Diseases
Liver Diseases
Neoplasms, Complex and Mixed
Neoplastic Syndromes, Hereditary

ClinicalTrials.gov processed this record on August 28, 2014