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Phase II Pilot Study of Low-Dose Vinblastine and Celecoxib in Combination With Standard Multiagent Chemotherapy in Patients With Newly Diagnosed Metastatic Ewing's Sarcoma Family of Tumors
Alternate Title Basic Trial Information Objectives Entry Criteria Expected Enrollment Outcomes Outline Trial Contact Information Registry Information
Alternate Title
Vinblastine, Celecoxib, and Combination Chemotherapy in Treating Patients With Newly-Diagnosed Metastatic Ewing's Sarcoma Family of Tumors
Basic Trial Information
Phase | Type | Status | Age | Protocol IDs |
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Phase II | Treatment | Closed | 50 and under (at diagnosis) | COG-AEWS02P1 AEWS02P1, NCT00061893 |
Objectives - Determine the feasibility and safety of low-dose vinblastine and celecoxib in combination with standard multiagent chemotherapy in patients with newly diagnosed metastatic Ewing's sarcoma family of tumors.
- Determine the event-free survival of patients treated with this regimen.
- Determine the pharmacokinetics of this regimen in these patients.
Entry Criteria Disease Characteristics:
- Newly diagnosed Ewing's sarcoma family of tumors of the bone or soft tissues
- Paraspinal tumors of extra-dural origin and Askin's tumor of the chest wall are eligible
- Metastatic disease, defined by the following criteria:
- Lesions are discontinuous from the primary tumor, are not regional lymph nodes, and do not share a body cavity with the primary tumor
- A single pulmonary or pleural nodule greater than 1 cm OR multiple nodules greater than 0.5 cm are considered evidence of pulmonary or pleural metastases (unless there is another clear medical explanation for these lesions)
- Contralateral pleural effusions are considered metastatic disease
- No CNS involvement
Prior/Concurrent Therapy:
Biologic therapy - No prior bone marrow or stem cell transplantation
Chemotherapy Endocrine therapy Radiotherapy Surgery Other - No other concurrent nonsteroidal anti-inflammatory medications, including salicylates
- No concurrent dexrazoxane unless approved by the study investigator
Patient Characteristics:
Age - 50 and under (at diagnosis)
Performance status - Lansky 50-100% (under 17 years of age)
- Karnofsky 50-100% (age 17 and over)
- Patients whose performance status is affected by a pathological fracture are allowed provided they are able to undergo treatment
Life expectancy Hematopoietic Hepatic - Bilirubin no greater than 1.5 times upper limit of normal (ULN)
- AST or ALT less than 5 times ULN
Renal - Creatinine adjusted according to age as follows*:
- No greater than 0.4 mg/dL (≤ 5 months)
- No greater than 0.5 mg/dL (6 months -11 months)
- No greater than 0.6 mg/dL (1 year-23 months)
- No greater than 0.8 mg/dL (2 years-5 years)
- No greater than 1.0 mg/dL (6 years-9 years)
- No greater than 1.2 mg/dL (10 years-12 years)
- No greater than 1.4 mg/dL (13 years and over [female])
- No greater than 1.5 mg/dL (13 years to 15 years [male])
- No greater than 1.7 mg/dL (16 years and over [male])
OR - Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min*
[Note: *Unless these values are related to renal insufficiency secondary to tumor involvement that is expected to improve once the tumor mass is smaller (e.g., pelvic mass causing obstructive hydronephrosis)] Cardiovascular - Shortening fraction at least 27% by echocardiogram
OR - Ejection fraction at least 50% by MUGA
Other - Not pregnant or nursing
- Fertile patients must use effective contraception
- Body surface area at least 0.4 m2
- No allergy to sulfa
- No aspirin hypersensitivity
- No asthma triad (asthma with nasal polyps, and urticaria)
- No other prior cancer, including nonmelanoma skin cancer
Expected Enrollment 36A total of 6-36 patients will be accrued for this study within 1.17 years. Outcomes Primary Outcome(s)Feasibility as measured by toxicity at study completion
Secondary Outcome(s)Event-free survival at 1 to 2 years following study completion
Outline This is a pilot, multicenter study. - Induction therapy: Patients receive the following alternating regimens:
Treatment repeats every 21 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity.
- Local control and consolidation therapy: Beginning on week 13, patients are assigned to 1 of 4 regimens based on disease status.
- Regimen A (surgery only): Patients who respond to induction chemotherapy undergo surgery on week 13. Patients then begin consolidation therapy on week 15 with the following alternating regimens:
- VAC (courses 5, 7, and 9): Patients receive VAC on weeks 15, 21, and 27.
- IE (courses 6, 8, 10, 12, and 14): Patients receive IE on weeks 18, 24, 30, 36, and 42.
- VC (courses 11 and 13): Patients receive vincristine IV and cyclophosphamide IV over 1 hour on weeks 33 and 39.
- Regimen B (radiotherapy only): Patients with unresectable lesions undergo radiotherapy once daily 5 days a week for up to approximately 6 weeks beginning on week 13. Patients also receive consolidation therapy beginning on week 13, with the following alternating regimens:
- VAC (courses 5, 9, and 11): Patients receive VAC on weeks 13, 25, and 31.
- IE (courses 6, 8, 10, 12, and 14): Patients receive IE on weeks 16, 22, 28, 34, and 40.
- VC (courses 7 and 13): Patients receive VC on weeks 19 and 37.
- Regimen C (surgery and radiotherapy): Patients who respond to induction chemotherapy undergo surgery on week 13. Patients who have inadequate margins after surgery undergo radiotherapy (as in regimen B) beginning on week 15. Patients also receive consolidation therapy, beginning on week 15, with the following alternating regimens:
- VAC (courses 5, 9, and 11): Patients receive VAC on weeks 15, 27, and 33.
- IE (courses 6, 8, 10, 12, and 14): Patients receive IE on weeks 18, 24, 30, 36, and 42.
- VC (courses 7 and 13): Patients receive VC on weeks 21 and 39.
- Regimen D (preoperative radiotherapy): Patients with bulky lesions who do not have a good clinical and radiographic response to induction therapy begin consolidation therapy on week 13 with VAC (course 5) and undergo concurrent radiotherapy as in regimen B. Patients then receive IE on weeks 16 and 19 for courses 6 and 7. Patients undergo surgery on week 22. Patients continue consolidation therapy with the following alternating regimens:
- VAC (courses 8 and 9): Patients receive VAC on weeks 24 and 27.
- IE (courses 10, 12, and 14): Patients receive IE on weeks 30, 36, and 42.
- VC (courses 11 and 13): Patients receive VC on weeks 33 and 39.
Patients receive G-CSF SC (as in induction therapy) during all consolidation courses. Consolidation therapy continues for 10 courses in the absence of disease progression or unacceptable toxicity.
- Vinblastine and celecoxib therapy: Throughout induction, local control, and consolidation therapies, patients also receive vinblastine IV 3 times a week (twice a week during the weeks that vincristine is given) and oral celecoxib twice daily, beginning on day 1 of course 1 and continuing until the completion of course 14.*
[Note: *To assess for safety, the first 6 patients enrolled receive vinblastine only during courses 1 and 2 and celecoxib is then added for all subsequent courses.]
Patients are followed every 3 months for 3 years and then every 6 months for 2 years.
Trial Contact Information
Trial Lead Organizations Children's Oncology Group | | | Judy Felgenhauer, MD, PS, Protocol chair | | Ph: 509-474-2777; 800-442-8534 |
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Registry Information | | Official Title | | A Pilot Study of Low-Dose Antiangiogenic Chemotherapy in Combination with Standard Multiagent Chemotherapy for Patients with Newly Diagnosed Metastatic Ewing Sarcoma Family of Tumors | | Trial Start Date | | 2004-04-23 | | Trial Completion Date | | 2009-06-29 (estimated) | | Registered in ClinicalTrials.gov | | NCT00061893 | | Date Submitted to PDQ | | 2003-04-09 | | Information Last Verified | | 2008-10-23 | | 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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