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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00831844




Registration number
NCT00831844
Ethics application status
Date submitted
28/01/2009
Date registered
28/01/2009
Date last updated
18/03/2015

Titles & IDs
Public title
Cixutumumab in Treating Patients With Relapsed or Refractory Solid Tumors
Scientific title
A Phase II Study of IMC-A12 (Anti-IGF-I Receptor Monoclonal Antibody, NSC #742460) in Children With Relapsed/Refractory Solid Tumors
Secondary ID [1] 0 0
NCI-2009-01170
Secondary ID [2] 0 0
NCI-2009-01170
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Adult Rhabdomyosarcoma 0 0
Adult Synovial Sarcoma 0 0
Childhood Hepatoblastoma 0 0
Childhood Synovial Sarcoma 0 0
Previously Treated Childhood Rhabdomyosarcoma 0 0
Recurrent Adrenocortical Carcinoma 0 0
Recurrent Adult Soft Tissue Sarcoma 0 0
Recurrent Childhood Liver Cancer 0 0
Recurrent Childhood Rhabdomyosarcoma 0 0
Recurrent Childhood Soft Tissue Sarcoma 0 0
Recurrent Ewing Sarcoma/Peripheral Primitive 0 0
Neuroectodermal Tumor 0 0
Recurrent Neuroblastoma 0 0
Recurrent Osteosarcoma 0 0
Recurrent Retinoblastoma 0 0
Recurrent Wilms Tumor and Other Childhood Kidney Tumors 0 0
Adult Rhabdomyosarcoma 0 0
Adult Synovial Sarcoma 0 0
Childhood Hepatoblastoma 0 0
Childhood Synovial Sarcoma 0 0
Previously Treated Childhood Rhabdomyosarcoma 0 0
Recurrent Adrenocortical Carcinoma 0 0
Recurrent Adult Soft Tissue Sarcoma 0 0
Recurrent Childhood Liver Cancer 0 0
Recurrent Childhood Rhabdomyosarcoma 0 0
Recurrent Childhood Soft Tissue Sarcoma 0 0
Recurrent Ewing Sarcoma/Peripheral Primitive 0 0
Neuroectodermal Tumor 0 0
Recurrent Neuroblastoma 0 0
Recurrent Osteosarcoma 0 0
Recurrent Retinoblastoma 0 0
Recurrent Wilms Tumor and Other Childhood Kidney Tumors 0 0
Condition category
Condition code
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 0 0 0 0
Bone
Cancer 0 0 0 0
Neuroendocrine tumour (NET)
Cancer 0 0 0 0
Children's - Other
Cancer 0 0 0 0
Liver
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Head and neck
Eye 0 0 0 0
Diseases / disorders of the eye
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - cixutumumab
Other interventions - laboratory biomarker analysis
Other interventions - cixutumumab
Other interventions - laboratory biomarker analysis

Experimental: Group 1 - Recurrent or Refractory Hepatoblastoma - Group 1 - Recurrent or Refractory Hepatoblastoma. 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.

Experimental: Group 2 - Recurrent or Refractory Synovial Sarcoma - Group 2 - Recurrent or Refractory Synovial Sarcoma. 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.

Experimental: Group 3 - Recurrent or Refractory Rhabdomyosarcoma - Group 3 - Recurrent or Refractory Rhabdomyosarcoma. 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.

Experimental: Grp 4-Recurrent or Refractory Adrenocortical Carcinoma - Group 4 - Recurrent or Refractory Adrenocortical Carcinoma. 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.

Experimental: Grp 5-Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor - Group 5 - Recurrent or Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor. 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.

Experimental: Grp 6 - Neuroblastoma-MIBG Positive Without Measurable Disease - Group 6 - Recurrent or Refractory Neuroblastoma -meta-iodobenzylguanidine (MIBG) Positive Without Measurable Disease. 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.

Experimental: Grp 7-Neuroblastoma with measurable disease - Group 7 - Recurrent or Refractory Neuroblastoma -With Measurable Disease. 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.

Experimental: Group 8 - Recurrent Osteosarcoma - Group 8 - Recurrent Osteosarcoma. 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.

Experimental: Group 9 - Recurrent or Refractory Wilms Tumor - Group 9 - Recurrent or Refractory Wilms Tumor. 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.

Experimental: Group 10 - Recurrent or Refractory Retinoblastoma - Group 10 - Recurrent or Refractory Retinoblastoma. 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.

Experimental: Group 1 - Recurrent or Refractory Hepatoblastoma - Group 1 - Recurrent or Refractory Hepatoblastoma. 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.

Experimental: Group 2 - Recurrent or Refractory Synovial Sarcoma - Group 2 - Recurrent or Refractory Synovial Sarcoma. 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.

Experimental: Group 3 - Recurrent or Refractory Rhabdomyosarcoma - Group 3 - Recurrent or Refractory Rhabdomyosarcoma. 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.

Experimental: Grp 4-Recurrent or Refractory Adrenocortical Carcinoma - Group 4 - Recurrent or Refractory Adrenocortical Carcinoma. 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.

Experimental: Grp 5-Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor - Group 5 - Recurrent or Refractory Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor. 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.

Experimental: Grp 6 - Neuroblastoma-MIBG Positive Without Measurable Disease - Group 6 - Recurrent or Refractory Neuroblastoma -meta-iodobenzylguanidine (MIBG) Positive Without Measurable Disease. 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.

Experimental: Grp 7-Neuroblastoma with measurable disease - Group 7 - Recurrent or Refractory Neuroblastoma -With Measurable Disease. 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.

Experimental: Group 8 - Recurrent Osteosarcoma - Group 8 - Recurrent Osteosarcoma. 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.

Experimental: Group 9 - Recurrent or Refractory Wilms Tumor - Group 9 - Recurrent or Refractory Wilms Tumor. 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.

Experimental: Group 10 - Recurrent or Refractory Retinoblastoma - Group 10 - Recurrent or Refractory Retinoblastoma. 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.


Other interventions: 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 interventions: laboratory biomarker analysis
Correlative studies

Other interventions: 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 interventions: laboratory biomarker analysis
Correlative studies

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Disease Response - Response rates will be calculated as the percent of patients whose best response is a Complete Response (CR) or Partial Response (PR).
Timepoint [1] 0 0
First six treatment cycles - 24 weeks
Primary outcome [2] 0 0
Disease Response - Response rates will be calculated as the percent of patients whose best response is a Complete Response (CR) or Partial Response (PR).
Timepoint [2] 0 0
First six treatment cycles - 24 weeks

Eligibility
Key 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
Minimum age
7 Months
Maximum age
30 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [2] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [3] 0 0
Royal Children's Hospital - Parkville
Recruitment hospital [4] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
4029 - Herston
Recruitment postcode(s) [3] 0 0
3052 - Parkville
Recruitment postcode(s) [4] 0 0
6008 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
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Connecticut
Country [5] 0 0
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Delaware
Country [6] 0 0
United States of America
State/province [6] 0 0
District of Columbia
Country [7] 0 0
United States of America
State/province [7] 0 0
Florida
Country [8] 0 0
United States of America
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Georgia
Country [9] 0 0
United States of America
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Hawaii
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United States of America
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Idaho
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Illinois
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Indiana
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Kentucky
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Maryland
Country [15] 0 0
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Massachusetts
Country [16] 0 0
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Michigan
Country [17] 0 0
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Minnesota
Country [18] 0 0
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Mississippi
Country [19] 0 0
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Missouri
Country [20] 0 0
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State/province [20] 0 0
Nebraska
Country [21] 0 0
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State/province [21] 0 0
Nevada
Country [22] 0 0
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New Jersey
Country [23] 0 0
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New Mexico
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New York
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North Carolina
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Ohio
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Oklahoma
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Oregon
Country [29] 0 0
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Pennsylvania
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South Carolina
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Tennessee
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Texas
Country [33] 0 0
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Utah
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Virginia
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Washington
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Wisconsin
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Canada
State/province [37] 0 0
British Columbia
Country [38] 0 0
Canada
State/province [38] 0 0
Manitoba
Country [39] 0 0
Canada
State/province [39] 0 0
Newfoundland and Labrador
Country [40] 0 0
Canada
State/province [40] 0 0
Nova Scotia
Country [41] 0 0
Canada
State/province [41] 0 0
Ontario
Country [42] 0 0
Canada
State/province [42] 0 0
Quebec
Country [43] 0 0
Canada
State/province [43] 0 0
Saskatchewan

Funding & Sponsors
Primary sponsor type
Government body
Name
National Cancer Institute (NCI)
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00831844
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Brenda Weigel, MD
Address 0 0
Children's Oncology Group
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications