Long Beach, California 90806

  • Recurrent Childhood Liver

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.


Study summary:

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.


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


Study is Available At:


Original ID:

NCI-2009-01170


NCT ID:

NCT00831844


Secondary ID:

NCI-2009-01170


Study Acronym:


Brief Title:

Cixutumumab in Treating Patients With Relapsed or Refractory Solid Tumors


Official Title:

A Phase II Study of IMC-A12 (Anti-IGF-I Receptor Monoclonal Antibody, NSC #742460) in Children With Relapsed/Refractory Solid Tumors


Overall Status:

Completed


Study Phase:

Phase 2


Genders:

Both


Minimum Age:

7 Months


Maximum Age:

30 Years


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

National Cancer Institute (NCI)


Oversight Authority:

United States: Food and Drug Administration


Reasons Why Stopped:


Study Type:

Interventional


Study Design:

Endpoint Classification: Safety/Efficacy Study, In


Number of Arms:

1


Number of Groups:

0


Total Enrollment:

114


Enrollment Type:

Actual


Overall Contact Information

Official Name:Brenda Weigel
Principal Investigator
Children's Oncology Group

Study Dates

Start Date:January 2009
Primary Completion Date:April 2013
Primary Completion Type:Actual
Verification Date:June 2014
Last Changed Date:June 18, 2014
First Received Date:January 28, 2009

Study Outcomes

Outcome Type:Primary Outcome
Measure:Toxicity, graded according to NCI CTCAE version 4.0
Time Frame:Up to 5 years
Safety Issues:True
Description: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.
Outcome Type:Primary Outcome
Measure:Response rate
Time Frame:24 weeks
Safety Issues:False
Description: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.

Study Interventions

Intervention Type:Biological
Name:cixutumumab
Description:Given IV
Arm Name:Treatment (cixutumumab)
Other Name:anti-IGF-1R recombinant monoclonal antibody IMC-A1
Intervention Type:Other
Name:laboratory biomarker analysis
Description:Correlative studies
Arm Name:Treatment (cixutumumab)

Study Arms

Study Arm Type:Experimental
Arm Name:Treatment (cixutumumab)
Description: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.

Study Agencies

Agency Class:NIH
Agency Type:Lead Sponsor
Agency Name:National Cancer Institute (NCI)

Sample and Retention Information

There are no available Sample and Retention Information

Study References

Reference Type:Results Reference
Citation:Malempati S, Weigel B, Ingle AM, Ahern CH, Carroll JM, Roberts CT, Reid JM, Schmechel S, Voss SD, Cho SY, Chen HX, Krailo MD, Adamson PC, Blaney SM. Phase I/II Trial and Pharmacokinetic Study of Cixutumumab in Pediatric Patients With Refractory Solid Tumors and Ewing Sarcoma: A Report From the Children's Oncology Group. J Clin Oncol. 2012 Jan 20;30(3):256-62. Epub 2011 Dec 19.
PMID:22184397

Data Source: ClinicalTrials.gov

Date Processed: April 03, 2020

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