High-Dose Combination Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Metastatic Rhabdomyosarcoma or Ectomesenchymoma - Full Text View

Sponsor:	Children's Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00354744

Purpose

RATIONALE: Drugs used in chemotherapy, such as vincristine, irinotecan, ifosfamide, etoposide, doxorubicin, cyclophosphamide, and dactinomycin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving high-dose combination chemotherapy together with radiation therapy may kill more tumor cells.

PURPOSE: This phase III trial is studying how well giving high-dose combination chemotherapy together with radiation therapy works in treating patients with newly diagnosed metastatic rhabdomyosarcoma or ectomesenchymoma.

Condition	Intervention	Phase
Sarcoma	Biological: dactinomycin Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: etoposide Drug: ifosfamide Drug: irinotecan hydrochloride Drug: vincristine sulfate Procedure: conventional surgery Radiation: radiation therapy	Phase III

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized
Official Title:	Intensive Multi-Agent Therapy, Including Dose-Compressed Cycles of Ifosfamide/Etoposide (IE) and Vincristine/Doxorubicin/Cyclophosphamide (VDC) 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 Doxorubicin Doxorubicin hydrochloride Etoposide Irinotecan U 101440E Etoposide phosphate Irinotecan hydrochloride Vincristine sulfate Ifosfamide

U.S. FDA Resources

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

Primary Outcome Measures:

Early disease control [ Designated as safety issue: No ]
Feasibility [ Designated as safety issue: No ]
Toxicity [ Designated as safety issue: Yes ]

Estimated Enrollment:	75
Study Start Date:	July 2006
Estimated Primary Completion Date:	August 2008 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Improve the early disease control interval for patients with newly diagnosed, high-risk, metastatic rhabdomyosarcoma or ectomesenchymoma using intensive, interval-compression therapy (comprising vincristine, irinotecan hydrochloride, ifosfamide, etoposide, doxorubicin hydrochloride, cyclophosphamide, and dactinomycin) that permits maximal early exposure to known effective agents.
Determine the feasibility of concurrent irinotecan hydrochloride and radiotherapy in these patients.
Assess immediate- and short-term side effects of concurrent irinotecan hydrochloride and radiotherapy in these patients.

Secondary

Expand the available data for response to irinotecan hydrochloride and vincristine in previously untreated patients with high-risk rhabdomyosarcoma.
Evaluate, prospectively, and validate gene expression values with the intent to define the best diagnostic predictors and more powerful prognostic classifiers.

OUTLINE: This is a prospective, nonrandomized, multicenter study. Patients are stratified according to prognostic factors predictive of outcome (e.g. histology, bone/bone marrow involvement, and number of metastatic sites).

Patients receive high-dose chemotherapy comprising vincristine 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 1 hour on days 1-5 of weeks 1, 4, 20, 23, 47, and 50; and ifosfamide IV over 1 hour and etoposide IV over 30-60 minutes on days 1-5 of weeks 9, 13, 17, 26, and 30. Patients also receive doxorubicin hydrochloride IV continuously over 24 hours 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; and dactinomycin IV over 1-5 minutes on day 1 of weeks 35, 38, 41, and 44 in the absence of disease progression or unacceptable toxicity. Patients also receive filgrastim (G-CSF) subcutaneously in weeks 7-9, 11-13, 15-17, 22, 26, 28-30, 32, 33, 35, 38, and 41-44 beginning 24-36 hours after the last chemotherapy dose and continuing until blood counts recover.

NOTE: *Patients undergoing early radiotherapy for intracranial extension do not receive doxorubicin in week 7.

Beginning at week 20 (or week 1 for patients with parameningeal tumors with intracranial extension [or spinal cord compression] requiring emergency radiotherapy), patients also undergo radiotherapy once a day, 5 days a week, for approximately 5½ weeks. Some patients may also undergo second-look surgery.

After completion of study treatment, patients are followed periodically for ≥ 10 years.

PROJECTED ACCRUAL: A total of 75 patients will be accrued for this study.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed high-risk rhabdomyosarcoma or ectomesenchymoma
- Prior enrollment on COG-D9902 to confirm local histological diagnosis required
  - Tissue must be submitted for pathologic review within 2 days of patient registration on COG-D9902
- Newly diagnosed disease
- Metastatic disease (stage IV, clinical group IV)
Has undergone initial surgical procedure (including biopsy) that provided the definitive diagnosis within the past 42 days
Parameningeal and paraspinal tumors allowed
- Patients with parameningeal (without intracranial extension [ICE]) and paraspinal tumors should begin study chemotherapy at week 1 and radiotherapy at week 20
Patients with evidence of ICE, as defined by contrast MRI showing that primary tumor touches, displaces, invades, distorts, or otherwise causes a signal abnormality of the dura in contiguity to the primary site in brain or spinal cord, are eligible
- ICE is presumed to exist if the cerebrospinal fluid cytopathology is positive for tumor at diagnosis
Patients requiring emergency radiotherapy are eligible
- Patients requiring emergency radiotherapy (for intracranial extension or spinal cord impingement) should begin study chemotherapy at week 1 (irinotecan hydrochloride and vincristine) concurrently with radiation therapy

PATIENT CHARACTERISTICS:

ECOG or Zubrod performance status (PS) 0-2 (Lansky PS 50-100% for patients < 10 years of age and Karnofsky PS 50-100% for patients ≥ 10 years of age)
Absolute neutrophil count ≥ 750/mm³*
Platelet count ≥ 75,000/mm³*
Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min (≥ 40 mL/min for infants < 1 year 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
SGPT < 2.5 times normal
Bilirubin < 1.5 mg/dL
Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 50% by MUGA
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during study and for ≥ 1 month after study completion
No evidence of uncontrolled infection
Able to undergo radiotherapy NOTE: *Abnormal blood counts allowed if there is bone marrow biopsy or aspirate proven bone marrow involvement by rhabdomyosarcoma

PRIOR CONCURRENT THERAPY:

No prior chemotherapy except steroids
No prior radiotherapy
No concurrent aprepitant during ifosfamide or doxorubicin hydrochloride chemotherapy
No concurrent dexrazoxane
No concurrent sargramostim (GM-CSF) or pegfilgrastim

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00354744

Show 166 Study Locations

Sponsors and Collaborators

Children's Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Brenda Weigel, MD	Masonic Cancer Center, University of Minnesota
Investigator:	Carola A. S. Arndt, MD	Mayo Clinic

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:	Children's Oncology Group - Group Chair Office ( Gregory H. Reaman )
Study ID Numbers:	CDR0000489215, COG-ARST0431
Study First Received:	July 19, 2006
Last Updated:	April 14, 2009
ClinicalTrials.gov Identifier:	NCT00354744 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

adult rhabdomyosarcoma
previously untreated childhood rhabdomyosarcoma
adult malignant mesenchymoma

childhood malignant mesenchymoma
metastatic childhood soft tissue sarcoma
stage IV adult soft tissue sarcoma

Additional relevant MeSH terms:

Anti-Infective Agents
Neoplasms, Muscle Tissue
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Irinotecan
Cyclophosphamide
Antibiotics, Antineoplastic
Etoposide phosphate
Anti-Bacterial Agents
Neoplasms, Connective and Soft Tissue
Dactinomycin
Therapeutic Uses
Alkylating Agents

Etoposide
Nucleic Acid Synthesis Inhibitors
Rhabdomyosarcoma
Neoplasms by Histologic Type
Myosarcoma
Mitosis Modulators
Vincristine
Enzyme Inhibitors
Antimitotic Agents
Immunosuppressive Agents
Doxorubicin
Camptothecin
Pharmacologic Actions
Protein Synthesis Inhibitors
Neoplasms

ClinicalTrials.gov processed this record on February 08, 2010