Cixutumumab in Treating Patients With Relapsed or Refractory Solid Tumors

Phase 2

Completed

• Conditions: Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Recurrent Adrenocortical Carcinoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Retinoblastoma; Recurrent Childhood Liver Cancer; Recurrent Osteosarcoma; Childhood Hepatoblastoma; Childhood Synovial Sarcoma

• Registration Number: NCT00831844
• Lead Sponsor: National Cancer Institute (NCI)

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.

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 Timeline

• Study Start: 2009-01
• Study First Submitted: 2009-01-28
• Study First Submitted QC: 2009-01-28
• Study First Posted: 2009-01-29
• Primary Completion: 2013-04
• Study Completion: 2013-10
• Status Verified: 2015-03
• Results First Submitted: 2015-03-18
• Results First Submitted QC: 2015-03-18
• Last Update Submitted: 2015-03-18
• Results First Posted: 2015-03-30
• Last Update Posted: 2015-03-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 116

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Disease Response	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).

Trial Locations

Locations (105)

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

University of Arkansas for Medical Sciences; 🇺🇸 Little Rock, Arkansas, United States

Southern California Permanente Medical Group; 🇺🇸 Downey, California, United States

Miller Children's Hospital; 🇺🇸 Long Beach, California, United States

Children's Hospital Los Angeles; 🇺🇸 Los Angeles, California, United States

Children's Hospital Central California; 🇺🇸 Madera, California, United States

Kaiser Permanente-Oakland; 🇺🇸 Oakland, California, United States

Childrens Hospital of Orange County; 🇺🇸 Orange, California, United States

Lucile Packard Children's Hospital Stanford University; 🇺🇸 Palo Alto, California, United States

University of California San Francisco Medical Center-Parnassus; 🇺🇸 San Francisco, California, United States

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