Cixutumumab in Treating Patients With Relapsed or Refractory Solid Tumors

Recurrent Neuroblastoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00831844
• Other study ID #: NCI-2009-01170
• Secondary ID: NCI-2009-01170CD
• Status: Completed
• Phase: Phase 2
• First received: January 28, 2009
• Last updated: March 18, 2015
• Start date: January 2009
• Est. completion date: October 2013

Study information

• Verified date: March 2015
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 116
• Est. completion date: October 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 7 Months to 30 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adrenocortical Carcinoma
• Adult Rhabdomyosarcoma
• Adult Synovial Sarcoma
• Childhood Hepatoblastoma
• Childhood Synovial Sarcoma
• Hepatoblastoma
• Kidney Neoplasms
• Neoplasms
• Neuroblastoma
• Neuroectodermal Tumor
• Neuroectodermal Tumors
• Neuroectodermal Tumors, Primitive
• Osteosarcoma
• 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
• Recurrent Neuroblastoma
• Recurrent Osteosarcoma
• Recurrent Retinoblastoma
• Recurrent Wilms Tumor and Other Childhood Kidney Tumors
• Retinoblastoma
• Rhabdomyosarcoma
• Sarcoma
• Sarcoma, Ewing
• Sarcoma, Synovial
• Wilms Tumor

Intervention

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:
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Royal Children's Hospital	Parkville	Victoria
Australia	Princess Margaret Hospital for Children	Perth	Western Australia
Australia	The Children's Hospital at Westmead	Westmead	New South Wales
Canada	IWK Health Centre	Halifax	Nova Scotia
Canada	Centre Hospitalier Universitaire Sainte-Justine	Montreal	Quebec
Canada	Allan Blair Cancer Centre	Regina	Saskatchewan
Canada	Janeway Child Health Centre	Saint John's	Newfoundland and Labrador
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	Hospital for Sick Children	Toronto	Ontario
Canada	British Columbia Children's Hospital	Vancouver	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba
United States	Children's Hospital Medical Center of Akron	Akron	Ohio
United States	Albany Medical Center	Albany	New York
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Texas Tech University Health Science Center-Amarillo	Amarillo	Texas
United States	C S Mott Children's Hospital	Ann Arbor	Michigan
United States	Children's Healthcare of Atlanta - Egleston	Atlanta	Georgia
United States	Sinai Hospital of Baltimore	Baltimore	Maryland
United States	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Saint Luke's Mountain States Tumor Institute	Boise	Idaho
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Carolinas Medical Center	Charlotte	North Carolina
United States	T C Thompson Children's Hospital	Chattanooga	Tennessee
United States	Lurie Children's Hospital-Chicago	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Rainbow Babies and Childrens Hospital	Cleveland	Ohio
United States	Palmetto Health Richland	Columbia	South Carolina
United States	University of Missouri - Ellis Fischel	Columbia	Missouri
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Medical City Dallas Hospital	Dallas	Texas
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Saint John Hospital and Medical Center	Detroit	Michigan
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Southern California Permanente Medical Group	Downey	California
United States	Lee Memorial Health System	Fort Myers	Florida
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	Helen DeVos Children's Hospital at Spectrum Health	Grand Rapids	Michigan
United States	Greenville Cancer Treatment Center	Greenville	South Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Connecticut Children's Medical Center	Hartford	Connecticut
United States	Penn State Hershey Children's Hospital	Hershey	Pennsylvania
United States	University of Hawaii	Honolulu	Hawaii
United States	Baylor College of Medicine	Houston	Texas
United States	Indiana University Medical Center	Indianapolis	Indiana
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Nemours Children's Clinic - Jacksonville	Jacksonville	Florida
United States	The Childrens Mercy Hospital	Kansas City	Missouri
United States	East Tennessee Childrens Hospital	Knoxville	Tennessee
United States	Nevada Cancer Research Foundation CCOP	Las Vegas	Nevada
United States	University of Kentucky	Lexington	Kentucky
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
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	Loyola University Medical Center	Maywood	Illinois
United States	Miami Children's Hospital	Miami	Florida
United States	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida
United States	Midwest Children's Cancer Center	Milwaukee	Wisconsin
United States	Children's Hospitals and Clinics of Minnesota - Minneapolis	Minneapolis	Minnesota
United States	University of Minnesota Medical Center-Fairview	Minneapolis	Minnesota
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	UMDNJ - Robert Wood Johnson University Hospital	New Brunswick	New Jersey
United States	Columbia University Medical Center	New York	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	New York University Langone Medical Center	New York	New York
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Childrens Hospital-King's Daughters	Norfolk	Virginia
United States	Kaiser Permanente-Oakland	Oakland	California
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Children's Hospital and Medical Center of Omaha	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Childrens Hospital of Orange County	Orange	California
United States	Florida Hospital	Orlando	Florida
United States	Nemours Childrens Clinic - Orlando	Orlando	Florida
United States	UF Cancer Center at Orlando Health	Orlando	Florida
United States	Lucile Packard Children's Hospital Stanford University	Palo Alto	California
United States	Nemours Children's Clinic - Pensacola	Pensacola	Florida
United States	Saint Jude Midwest Affiliate	Peoria	Illinois
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	University of Rochester	Rochester	New York
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	All Children's Hospital	Saint Petersburg	Florida
United States	Primary Children's Hospital	Salt Lake City	Utah
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	University of California San Francisco Medical Center-Parnassus	San Francisco	California
United States	Seattle Children's Hospital	Seattle	Washington
United States	Providence Sacred Heart Medical Center and Children's Hospital	Spokane	Washington
United States	Southern Illinois University	Springfield	Illinois
United States	State University of New York Upstate Medical University	Syracuse	New York
United States	Mary Bridge Children's Hospital and Health Center	Tacoma	Washington
United States	Saint Joseph Children's Hospital of Tampa	Tampa	Florida
United States	Scott and White Memorial Hospital	Temple	Texas
United States	New York Medical College	Valhalla	New York
United States	Lombardi Comprehensive Cancer Center at Georgetown University	Washington	District of Columbia
United States	Saint Mary's Hospital	West Palm Beach	Florida
United States	Alfred I duPont Hospital for Children	Wilmington	Delaware

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Australia,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease Response	Response rates will be calculated as the percent of patients whose best response is a Complete Response (CR) or Partial Response (PR).	First six treatment cycles - 24 weeks	No