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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01055314




Registration number
NCT01055314
Ethics application status
Date submitted
22/01/2010
Date registered
25/01/2010
Date last updated
29/08/2017

Titles & IDs
Public title
Temozolomide, Cixutumumab, and Combination Chemotherapy in Treating Patients With Metastatic Rhabdomyosarcoma
Scientific title
A Pilot Study to Evaluate Novel Agents (Temozolomide and Cixutumumab [IMC-A12, Anti-IGF-IR Monoclonal Antibody NSC # 742460]) in Combination With Intensive Multi-agent Interval Compressed Therapy for Patients With High-Risk Rhabdomyosarcoma
Secondary ID [1] 0 0
NCI-2011-02005
Secondary ID [2] 0 0
NCI-2011-02005
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Adult Rhabdomyosarcoma 0 0
Childhood Alveolar Rhabdomyosarcoma 0 0
Childhood Embryonal Rhabdomyosarcoma 0 0
Metastatic Childhood Soft Tissue Sarcoma 0 0
Stage IV Adult Soft Tissue Sarcoma 0 0
Untreated Childhood Rhabdomyosarcoma 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
Children's - Other

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Cixutumumab
Treatment: Drugs - Cyclophosphamide
Other interventions - Dactinomycin
Treatment: Drugs - Doxorubicin Hydrochloride
Treatment: Drugs - Etoposide
Treatment: Drugs - Ifosfamide
Treatment: Drugs - Irinotecan Hydrochloride
Other interventions - Laboratory Biomarker Analysis
Treatment: Drugs - Temozolomide
Treatment: Drugs - Vincristine Sulfate Liposome

Experimental: Group 1 (chemotherapy, radiation therapy, cixutumumab) - Patients receive vincristine sulfate IV over 1 minute on day 1 of weeks 1-5, 7, 8, 11, 12, 15, 16, 20-24, 28, 29, 32, 33, 35, 38, 41-44, 47, 48, 50, and 51; irinotecan hydrochloride IV over 90 minutes on days 1-5 of weeks 1, 4, 20, 23, 47, and 50; ifosfamide IV over 1 hour and etoposide IV over 1-2 hours on days 1-5 of weeks 9, 13, 17, 26, and 30; doxorubicin hydrochloride IV over 1-15 minutes on days 1 and 2 of weeks 7, 11, 15, 28, and 32; cyclophosphamide IV over 30-60 minutes on day 1 of weeks 7, 11, 15, 28, 32, 35, 38, 41, and 44; dactinomycin IV over 1-5 minutes on day 1 of weeks 35, 38, 41, and 44; and cixutumumab IV over 1 hour on day 1 of weeks 1-51. Patients also undergo radiation therapy on days 1-5 of weeks 20-24.

Experimental: Group 2 (chemotherapy, radiation therapy, temozolomide) - Patients receive vincristine sulfate, irinotecan hydrochloride, ifosfamide, etoposide, doxorubicin hydrochloride, cyclophosphamide, and dactinomycin and undergo radiation therapy as in group 1. Patients also receive temozolomide PO on days 1-5 of weeks 1, 4, 20, 23, 47, and 50.


Other interventions: Cixutumumab
Given IV

Treatment: Drugs: Cyclophosphamide
Given IV

Other interventions: Dactinomycin
Given IV

Treatment: Drugs: Doxorubicin Hydrochloride
Given IV

Treatment: Drugs: Etoposide
Given IV

Treatment: Drugs: Ifosfamide
Given IV

Treatment: Drugs: Irinotecan Hydrochloride
Given IV

Other interventions: Laboratory Biomarker Analysis
Correlative studies

Treatment: Drugs: Temozolomide
Given PO

Treatment: Drugs: Vincristine Sulfate Liposome
Given IV

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Feasibility of the Addition of Cixutumumab to Chemotherapy Determined by Patient Enrollment - Proportion of no Grade 3+ cardiac toxicity.
Timepoint [1] 0 0
From start to week 26 of therapy
Primary outcome [2] 0 0
Feasibility of the Addition of Temozolomide to Chemotherapy Determined by Patient Enrollment - Proportion of no Grade 4+ non-hematologic toxicity.
Timepoint [2] 0 0
From start to week 26 of therapy
Primary outcome [3] 0 0
Incidence of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 4.0 - Number of patients with grade 3+ adverse events (AE) during therapy. (Grade 3+) = (Grade 3 + Grade 4 + Grade 5) . Grade 3: Severe and undesirable AE; Grade 4: Life threatening or disabling AE; Grade 5: Death related to AE.
Timepoint [3] 0 0
Up to 54 weeks
Primary outcome [4] 0 0
Event-Free Survival - Probability of no relapse, secondary malignancy, or death after 3 years in the study.
Timepoint [4] 0 0
3 years
Secondary outcome [1] 0 0
Response Rate (CR + PR) - Proportion of patients with complete or partial response. Complete Response (CR): Complete disappearance of the tumor confirmed at > 4 weeks. Partial Response (PR): At least 64% decrease in volume compared to the measurement obtained at study enrollment; Overall Response (OR) = CR + PR.
Timepoint [1] 0 0
From the start of treatment until a maximum of 2 cycles (21 days per cycle) of treatment in the absence of disease progression or unacceptable toxicities

Eligibility
Key inclusion criteria
- Patients must be eligible for, and enrolled on D9902 prior to enrollment on ARST08P1

- Patients with newly diagnosed, biopsy-proven metastatic rhabdomyosarcoma or
ectomesenchymoma (stage IV, clinical group IV) are eligible for this study; patients
with stage IV, clinical group IV RMS with parameningeal and paraspinal primary tumors,
including those with intracranial extension (ICE) are eligible for ARST08P1; ICE is
defined by contrast magnetic resonance imaging (MRI) showing that the primary tumor
touches, displaces, invades, distorts, or otherwise causes signal abnormality of the
dura in brain or spinal cord in contiguity to the primary site; ICE is also presumed
to exist if the cerebrospinal fluid (CSF) cytopathology is positive for tumor at
diagnosis

- Patients must have a performance status corresponding to Eastern Cooperative Oncology
Group (ECOG) scores of 0, 1, or 2; use Karnofsky for patients > 16 years of age and
Lansky for patients =< 16 years of age

- No prior chemotherapy or radiotherapy except for use of corticosteroids or emergent
radiation therapy; patients requiring emergency radiation are eligible

- Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
mL/min/1.73m^2 OR maximum serum creatinine 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)

- 1.0 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)

- Patients with urinary tract obstruction by tumor must meet the renal function criteria
listed above AND must have unimpeded urinary flow established via decompression of the
obstructed portion of the urinary tract

- Total bilirubin =< 1.5 x upper limit of normal (ULN) for age, unless there is evidence
of biliary obstruction by the tumor

- Shortening fraction >= 27% by echocardiogram (ECHO) OR ejection fraction >= 50% by
radionuclide angiogram

- Absolute neutrophil count (ANC) >= 750/uL; abnormal blood counts are permissible if
there is bone marrow biopsy or aspirate proven bone marrow involvement by
rhabdomyosarcoma

- Platelet count >= 75,000/uL; abnormal blood counts are permissible if there is bone
marrow biopsy or aspirate proven bone marrow involvement by rhabdomyosarcoma

- Sexually active patients of childbearing potential must agree to use effective
contraception during therapy (Pilots 1 and 2) and for at least 3 months after the last
dose of IMC-A12 (Pilots 1)
Minimum age
No limit
Maximum age
49 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Female patients who are pregnant are not eligible

- Female patients who are breastfeeding are not eligible; female patients who are
lactating must agree to stop breastfeeding to participate in this study

- Patients receiving growth hormone therapy are not eligible

- Patients with known type I or type II diabetes mellitus are not eligible for
enrollment on Pilot 1

- Patients with evidence of uncontrolled infection are not eligible

- All patients and/or their parents or legal guardians must sign a written informed
consent

- All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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
Parallel
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,WA
Recruitment hospital [1] 0 0
Sydney Children's Hospital - Randwick
Recruitment hospital [2] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [3] 0 0
Royal Brisbane and Women's Hospital - Herston
Recruitment hospital [4] 0 0
Royal Children's Hospital-Brisbane - Herston
Recruitment hospital [5] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4029 - Herston
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
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
Arkansas
Country [4] 0 0
United States of America
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California
Country [5] 0 0
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Colorado
Country [6] 0 0
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Connecticut
Country [7] 0 0
United States of America
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Delaware
Country [8] 0 0
United States of America
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District of Columbia
Country [9] 0 0
United States of America
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Florida
Country [10] 0 0
United States of America
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Georgia
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Hawaii
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Idaho
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Illinois
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Indiana
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Iowa
Country [16] 0 0
United States of America
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Kentucky
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Louisiana
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Maryland
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Massachusetts
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Michigan
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Minnesota
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Mississippi
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Missouri
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Nevada
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New Jersey
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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
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Pennsylvania
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Rhode Island
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South Carolina
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South Dakota
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Tennessee
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Texas
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Utah
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Vermont
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Virginia
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Washington
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West Virginia
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Wisconsin
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Canada
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Alberta
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Canada
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British Columbia
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Canada
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Manitoba
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Canada
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Nova Scotia
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Canada
State/province [48] 0 0
Ontario
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Canada
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Quebec
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Canada
State/province [50] 0 0
Saskatchewan
Country [51] 0 0
New Zealand
State/province [51] 0 0
Auckland

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

Ethics approval
Ethics application status

Summary
Brief summary
This randomized pilot clinical trial is studying the side effects and how well giving
temozolomide and cixutumumab together with combination chemotherapy works in treating
patients with metastatic rhabdomyosarcoma. Drugs used in chemotherapy, such as temozolomide,
work in different ways to stop the growth of tumor cells, either by killing the cells or by
stopping them from dividing. 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. Giving
temozolomide and cixutumumab together with combination chemotherapy may kill more tumor
cells.
Trial website
https://clinicaltrials.gov/show/NCT01055314
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Suman Malempati, 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