Trial record 1 of 1 for:    COG ARST08P1
Previous Study | Return to List | Next Study

Temozolomide, Cixutumumab, and Combination Chemotherapy in Treating Patients With Metastatic Rhabdomyosarcoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01055314
First received: January 22, 2010
Last updated: August 12, 2014
Last verified: March 2014

January 22, 2010
August 12, 2014
January 2010
December 2016   (final data collection date for primary outcome measure)
  • Feasibility of the addition of cixutumumab to chemotherapy determined by patient enrollment [ Time Frame: Up to 54 weeks ] [ Designated as safety issue: No ]
  • Feasibility of the addition of temozolomide to chemotherapy determined by patient enrollment [ Time Frame: Up to 54 weeks ] [ Designated as safety issue: No ]
  • Incidence of adverse events assessed by Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Feasibility [ Designated as safety issue: No ]
  • Immediate and short-term side effects [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01055314 on ClinicalTrials.gov Archive Site
  • Response rate assessed by Response Evaluation Criteria for Solid Tumors (RECIST) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    An O'Brien-Fleming monitoring boundary (truncated at 3 standard deviations) and a spending function approach will be employed for interim monitoring of efficacy. A futility analysis will also be performed, testing a 'null hypothesis' that the relative risk of failure with this therapy is 0.60 (compared to the ID/IE therapy experience), with consideration of suspension of accrual should this hypothesis be rejected at any of the scheduled interim looks at a significance level of 0.005.
  • Event-free survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Preliminary response rate [ Designated as safety issue: No ]
  • Preliminary efficacy [ Designated as safety issue: No ]
  • Effectiveness of FDG PET in detecting metastatic disease [ Designated as safety issue: No ]
  • Levels of IGF-I, IGF-II, and IGF-BP3 [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Temozolomide, Cixutumumab, and Combination Chemotherapy in Treating Patients With Metastatic Rhabdomyosarcoma
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

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.

PRIMARY OBJECTIVES:

I. To determine the feasibility of administering IMC-A12 (cixutumumab) in combination with a multi-agent intensive chemotherapy regimen for the treatment of high-risk rhabdomyosarcoma (RMS).

II. To determine the feasibility of adding temozolomide to vincristine (vincristine sulfate)/irinotecan (irinotecan hydrochloride) cycles in patients with high-risk RMS.

III. To assess immediate and short-term side effects of delivery of concurrent temozolomide-vincristine-irinotecan with irradiation in patients with high-risk RMS.

SECONDARY OBJECTIVES:

I. To gain a preliminary estimate of the response rate to IMC-A12 or temozolomide plus vincristine/irinotecan in previously untreated high-risk RMS.

II. To obtain preliminary efficacy data for IMC-A12 or temozolomide in combination with a multi-agent interval compressed chemotherapy regimen in previously untreated high-risk RMS.

III. To determine the effectiveness of detecting metastatic disease with fludeoxyglucose F 18 positron emission tomography (FDG PET) and to compare assessment of response using standard imaging techniques with response assessed by FDG PET.

IV. To assess changes in serum levels of insulin-like growth factor (IGF)-I, IGF-II, IGF-BP3 as biomarkers of IGF-IR inhibition.

OUTLINE: This is a dose-escalation study of cixutumumab. Patients are assigned to 1 of 2 treatment groups according to the timing of their enrollment onto the study.

GROUP 1: Patients receive vincristine sulfate intravenously (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.

GROUP 2: 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 orally (PO) on days 1-5 of weeks 1, 4, 20, 23, 47, and 50.

GROUP 3: Patients receive vincristine sulfate, irinotecan hydrochloride, ifosfamide, etoposide, doxorubicin hydrochloride, cyclophosphamide, dactinomycin, and cixutumumab and undergo radiation therapy* as in group 1. Patients also receive temozolomide as in group 2. (Discontinued as of January 2013)

NOTE: *Patients with parameningeal tumors and evidence of intracranial extension or those requiring emergency radiotherapy may receive radiation therapy starting in week 1; cixutumumab should be withheld during radiation therapy.

After completion of study therapy, patients are followed up at 3 weeks and then periodically for up to 5 years.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Adult Rhabdomyosarcoma
  • Alveolar Childhood Rhabdomyosarcoma
  • Embryonal Childhood Rhabdomyosarcoma
  • Metastatic Childhood Soft Tissue Sarcoma
  • Previously Untreated Childhood Rhabdomyosarcoma
  • Stage IV Adult Soft Tissue Sarcoma
  • Biological: cixutumumab
    Given IV
    Other Names:
    • anti-IGF-1R recombinant monoclonal antibody IMC-A12
    • IMC-A12
  • Drug: doxorubicin hydrochloride
    Given IV
    Other Names:
    • ADM
    • ADR
    • Adria
  • Drug: irinotecan hydrochloride
    Given IV
    Other Names:
    • Campto
    • Camptosar
    • CPT-11
    • irinotecan
    • U-101440E
  • Drug: liposomal vincristine sulfate
    Given IV
    Other Names:
    • liposomal vincristine
    • Marqibo
    • vincristine liposomal
    • vincristine sulfate liposome injection
  • Drug: ifosfamide
    Given IV
    Other Names:
    • Cyfos
    • Holoxan
    • IFF
    • IFX
    • IPP
  • Drug: etoposide
    Given IV
    Other Names:
    • EPEG
    • VP-16
    • VP-16-213
  • Drug: cyclophosphamide
    Given IV
    Other Names:
    • CPM
    • CTX
    • Cytoxan
    • Endoxan
    • Endoxana
  • Biological: dactinomycin
    Given IV
    Other Names:
    • ACT-D
    • actinomycin C1
    • AD
    • Cosmegen
    • DACT
  • Drug: temozolomide
    Given PO
    Other Names:
    • SCH 52365
    • Temodal
    • Temodar
    • TMZ
  • Other: laboratory biomarker analysis
    Correlative studies
  • 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.
    Interventions:
    • Biological: cixutumumab
    • Drug: doxorubicin hydrochloride
    • Drug: irinotecan hydrochloride
    • Drug: liposomal vincristine sulfate
    • Drug: ifosfamide
    • Drug: etoposide
    • Drug: cyclophosphamide
    • Biological: dactinomycin
    • Other: laboratory biomarker analysis
  • 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.
    Interventions:
    • Drug: doxorubicin hydrochloride
    • Drug: irinotecan hydrochloride
    • Drug: liposomal vincristine sulfate
    • Drug: ifosfamide
    • Drug: etoposide
    • Drug: cyclophosphamide
    • Biological: dactinomycin
    • Drug: temozolomide
    • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
180
Not Provided
December 2016   (final data collection date for primary outcome measure)

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)

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
Both
up to 49 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Canada,   New Zealand
 
NCT01055314
NCI-2011-02005, NCI-2011-02005, CDR0000663937, COG-ARST08P1, ARST08P1, ARST08P1, U10CA098543
No
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Suman Malempati Children's Oncology Group
National Cancer Institute (NCI)
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP