Temozolomide, Cixutumumab, and Combination Chemotherapy in Treating Patients With Metastatic Rhabdomyosarcoma - Full Text View

Sponsor:	Children's Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT01055314

Purpose

RATIONALE: 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.

PURPOSE: This 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.

Condition	Intervention
Sarcoma	Biological: cixutumumab Biological: dactinomycin Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: etoposide Drug: ifosfamide Drug: irinotecan hydrochloride Drug: temozolomide Drug: vincristine sulfate

Study Type:	Interventional
Study Design:	Masking: Open Label Primary Purpose: Treatment
Official Title:	A Pilot Study to Evaluate Novel Agents (Temozolomide and Cixutumumab [IMC-A12, Anti-IGF-IR Monoclonal Antibody, IND #100947, NSC #742460]) in Combination With Intensive Multi-Agent Interval Compressed Therapy for Patients With High-Risk Rhabdomyosarcoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Soft Tissue Sarcoma

Drug Information available for: Cyclophosphamide Dactinomycin Vincristine sulfate Ifosfamide Doxorubicin Doxorubicin hydrochloride Etoposide Temozolomide Irinotecan Etoposide phosphate Irinotecan hydrochloride

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Feasibility [ Designated as safety issue: No ]
Immediate and short-term side effects [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

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 ]

Estimated Enrollment:	195
Study Start Date:	January 2010
Estimated Primary Completion Date:	July 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Group 1 Patients receive vincristine sulfate IV 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 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 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 radiotherapy on days 1-5 of weeks 20-24.	Biological: cixutumumab Given IV Biological: dactinomycin Given IV Drug: cyclophosphamide Given IV Drug: doxorubicin hydrochloride Given IV Drug: etoposide Given IV Drug: ifosfamide Given IV Drug: irinotecan hydrochloride Given IV Drug: vincristine sulfate Given IV
Experimental: Group 2 Patients receive vincristine sulfate, irinotecan hydrochloride, ifosfamide, etoposide, doxorubicin hydrochloride, cyclophosphamide, and dactinomycin and undergo radiotherapy as in group 1. Patients also receive oral temozolomide on days 1-5 of weeks 1, 4, 20, 23, 47, and 50.	Biological: dactinomycin Given IV Drug: cyclophosphamide Given IV Drug: doxorubicin hydrochloride Given IV Drug: etoposide Given IV Drug: ifosfamide Given IV Drug: irinotecan hydrochloride Given IV Drug: temozolomide Given orally Drug: vincristine sulfate Given IV
Experimental: Group 3 Patients receive vincristine sulfate, irinotecan hydrochloride, ifosfamide, etoposide, doxorubicin hydrochloride, cyclophosphamide, dactinomycin, and cixutumumab and undergo radiotherapy as in group 1. Patients also receive temozolomide as in group 2.	Biological: cixutumumab Given IV Biological: dactinomycin Given IV Drug: cyclophosphamide Given IV Drug: doxorubicin hydrochloride Given IV Drug: etoposide Given IV Drug: ifosfamide Given IV Drug: irinotecan hydrochloride Given IV Drug: temozolomide Given orally Drug: vincristine sulfate Given IV

Detailed Description:

OBJECTIVES:

Primary

To determine the feasibility of administering cixutumumab in combination with an intensive multi-agent interval compressed chemotherapy regimen for the treatment of high-risk metastatic rhabdomyosarcoma (RMS).
To determine the feasibility of adding temozolomide to vincristine and irinotecan in these patients.
To assess immediate and short-term side effects of concurrent temozolomide, vincristine, and irinotecan with radiotherapy in these patients.
To determine the feasibility of administering cixutumumab in combination with an intensive multi-agent interval compressed chemotherapy regimen comprising temozolomide, vincristine, and irinotecan in these patients.

Secondary

To gain a preliminary estimate of the response rate to cixutumumab and/or temozolomide, vincristine, and irinotecan in these patients.
To obtain preliminary efficacy data for cixutumumab and/or temozolomide in combination with an intensive multi-agent interval compressed chemotherapy regimen in these patients.
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.
To assess changes in serum levels of IGF-I, IGF-II, IGF-BP3 as biomarkers of IGF-IR inhibition.

OUTLINE: This is a multicenter, dose-escalation study of cixutumumab. Patients are assigned to 1 of 3 treatment groups according to the timing of their enrollment onto the study.

Group 1: Patients receive vincristine sulfate IV 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 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 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 radiotherapy* 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 radiotherapy* as in group 1. Patients also receive oral temozolomide 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 radiotherapy* as in group 1. Patients also receive temozolomide as in group 2.
NOTE: *Patients with parameningeal tumors and evidence of intracranial extension or those requiring emergency radiotherapy may receive radiotherapy starting in week 1; cixutumumab should be withheld during radiotherapy.

Patients in groups 1 and 3 may undergo blood sample collection at baseline and after completion of week 6 for IGF-I, IGF-II, and IGF-BP3 biomarker analysis.

After completion of study therapy, patients are followed up periodically for up to 10 years.

Eligibility

Ages Eligible for Study:	up to 49 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Newly diagnosed, biopsy-confirmed metastatic rhabdomyosarcoma (RMS) or ectomesenchymoma, including the following:
- Embryonal RMS (for patients 10 to 49 years of age)
- Alveolar RMS or ectomesenchymoma (for patients under 50 years of age)
RMS with parameningeal and paraspinal primary tumors, including those with intracranial extension by contrast 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, are allowed
Has undergone initial surgery (including biopsy) that provided the definitive diagnosis within the past 42 days
Enrollment on COG-D9902 required

PATIENT CHARACTERISTICS:

ECOG performance status (PS) 0-2
ANC ≥ 750/μL*
Platelet count ≥ 75,000/μL*
Creatinine clearance or radioisotope GFR ≥ 70 mL/min 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)
Urinary tract obstruction by tumor allowed provided the above renal function criteria are met AND there is unimpeded urinary flow established via decompression of the obstructed portion of the urinary tract
Total bilirubin ≤ 1.5 times upper limit of normal (ULN) for age (unless there is evidence of biliary obstruction by the tumor)
Shortening fraction ≥ 27% by ECHO OR ejection fraction ≥ 50% by radionuclide angiogram
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for ≥ 3 months after the last dose of cixutumumab
No uncontrolled infection
No known type I or type II diabetes mellitus (for patients enrolled in groups 1 or 3) NOTE: *Abnormal blood counts allowed provided bone marrow biopsy or aspirate confirm bone marrow involvement by RMS

PRIOR CONCURRENT THERAPY:

No prior chemotherapy or radiotherapy except corticosteroids or emergent radiotherapy
No concurrent growth hormone therapy
No concurrent sargramostim

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01055314

Show 127 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Suman Malempati, MD

Doernbecher Children's Hospital at Oregon Health and Science University

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Suman Malempati, Doernbecher Children's Hospital at Oregon Health and Science University
ClinicalTrials.gov Identifier:	NCT01055314 History of Changes
Other Study ID Numbers:	CDR0000663937, COG-ARST08P1
Study First Received:	January 22, 2010
Last Updated:	May 18, 2012
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

adult rhabdomyosarcoma
alveolar childhood rhabdomyosarcoma
embryonal childhood rhabdomyosarcoma

previously untreated childhood rhabdomyosarcoma
metastatic childhood soft tissue sarcoma
stage IV adult soft tissue sarcoma

Additional relevant MeSH terms:

Rhabdomyosarcoma
Sarcoma
Myosarcoma
Neoplasms, Muscle Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Dactinomycin
Doxorubicin
Etoposide phosphate
Isophosphamide mustard
Temozolomide
Irinotecan
Cyclophosphamide
Etoposide

Ifosfamide
Vincristine
Dacarbazine
Camptothecin
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Anti-Bacterial Agents
Anti-Infective Agents
Immunosuppressive Agents

ClinicalTrials.gov processed this record on May 23, 2012