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Phase III Study of High-Dose Combination Chemotherapy Comprising Vincristine, Irinotecan Hydrochloride, Ifosfamide, Etoposide, Doxorubicin Hydrochloride, Cyclophosphamide, and Dactinomycin and Radiotherapy in Patients With Newly Diagnosed, High-Risk, Metastatic Rhabdomyosarcoma or Ectomesenchymoma
Alternate Title Basic Trial Information Objectives Entry Criteria Expected Enrollment Outcomes Outline Trial Contact Information Related Information Registry Information
Alternate Title
High-Dose Combination Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Metastatic Rhabdomyosarcoma or Ectomesenchymoma
Basic Trial Information
Phase | Type | Status | Age | Protocol IDs |
---|
Phase III | Treatment | Closed | Under 50 | COG-ARST0431 ARST0431, NCT00354744 |
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.
Entry 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
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
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] Expected Enrollment 75A total of 75 patients will be accrued for this study. Outcomes Primary Outcome(s)Early disease control Feasibility Toxicity
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.
Trial Contact Information
Trial Lead Organizations Children's Oncology Group | | | Brenda Weigel, MD, Protocol chair | | Ph: 612-626-5501; 888-226-2376 |
| | Carola Arndt, MD, Protocol co-chair | | | |
Related Information PDQ® clinical trial COG-D9902
Registry Information | | 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 | | Trial Start Date | | 2006-07-17 | | Trial Completion Date | | 2008-08-05 (estimated) | | Registered in ClinicalTrials.gov | | NCT00354744 | | Date Submitted to PDQ | | 2006-06-01 | | Information Last Verified | | 2008-10-20 | | NCI Grant/Contract Number | | CA98543 |
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol. Back to Top |
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