Two Regimens of Combination Chemotherapy in Treating Younger Patients With Newly Diagnosed Localized Ewing Sarcoma Family of Tumors
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Purpose
This clinical trial is studying the side effects of two regimens of combination chemotherapy and to see how well they work in treating patients with newly diagnosed localized Ewing sarcoma family of tumors. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) and giving the drugs in different ways may kill more tumor cells.
| Condition | Intervention |
|---|---|
|
Ewing Sarcoma of Bone Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor |
Other: radiation therapy Other: therapeutic conventional surgery Drug: etoposide Drug: ifosfamide Drug: doxorubicin hydrochloride Drug: cyclophosphamide Drug: vincristine sulfate Drug: topotecan hydrochloride Biological: filgrastim |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Pilot Study of Chemotherapy Intensification by Adding Vincristine, Topotecan and Cyclophosphamide to Standard Chemotherapy Agents With an Interval Compression Schedule in Newly Diagnosed Patients With Localized Ewing Sarcoma Family of Tumors |
- Incidence of death from complications during therapy or within one month of terminating therapy [ Time Frame: Up to 1 month ] [ Designated as safety issue: Yes ]
- Incidence rate of dose-limiting toxicity during therapy [ Time Frame: Week 12 ] [ Designated as safety issue: Yes ]
- Incidence rate of dose-limiting toxicity during therapy [ Time Frame: Week 22 ] [ Designated as safety issue: Yes ]
- Incidence rate of dose-limiting toxicity during therapy [ Time Frame: Week 28 ] [ Designated as safety issue: Yes ]
- Incidence rate of dose-limiting toxicity during therapy [ Time Frame: Week 37 ] [ Designated as safety issue: Yes ]
- The time from the start of therapy to the initiation of local control measures planned [ Time Frame: Week 13 ] [ Designated as safety issue: No ]
- Sustained dose compression [ Time Frame: 1 month ] [ Designated as safety issue: No ]
- Estimation of event-free survival [ Time Frame: The time from enrollment on study until disease progression, occurrence of second malignant neoplasm or death, assessed up to 10 years ] [ Designated as safety issue: No ]Characterized by the method of Kaplan and Meier.
- Survival [ Time Frame: The time from enrollment on the study until death or last contact, assessed up to 10 years ] [ Designated as safety issue: No ]Characterized by the method of Kaplan and Meier.
| Enrollment: | 35 |
| Study Start Date: | March 2008 |
| Primary Completion Date: | July 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Treatment (combination chemotherapy)
See Detailed Description
|
Other: radiation therapy
Undergo radiation therapy
Other Names:
Other: therapeutic conventional surgery
Undergo surgery
Drug: etoposide
Given IV
Other Names:
Drug: ifosfamide
Given IV
Other Names:
Drug: doxorubicin hydrochloride
Given IV
Other Names:
Drug: cyclophosphamide
Given IV
Other Names:
Drug: vincristine sulfate
Given IV
Other Names:
Drug: topotecan hydrochloride
Given IV
Other Names:
Biological: filgrastim
Given SC
Other Names:
|
Detailed Description:
PRIMARY OBJECTIVES:
I. To assess the feasibility and safety of adding interval-compressed vincristine, topotecan hydrochloride, and cyclophosphamide to a treatment protocol utilizing interval compression of vincristine, doxorubicin hydrochloride, cyclophosphamide, ifosfamide, and etoposide in patients with localized Ewing sarcoma family of tumors.
SECONDARY OBJECTIVES:
I. To estimate the event-free survival in patients treated with this regimen.
OUTLINE: This is a multicenter study.
INDUCTION THERAPY (WEEKS 1-12): Patients receive vincristine IV on day 1 in weeks 1, 2, 5, 6, 9, 10, 11, and 12; topotecan hydrochloride IV over 30 minutes on days 1-5 in weeks 1 and 9; cyclophosphamide IV over 1 hour on days 1-5 in weeks 1 and 9 and on day 1 in weeks 5 and 11; ifosfamide IV over 1 hour on days 1-5 in weeks 3 and 7; etoposide IV over 1 hour on days 1-5 in weeks 3 and 7; and doxorubicin hydrochloride IV over 15 minutes on days 1 and 2 in weeks 5 and 11. Patients also receive filgrastim (G-CSF) subcutaneously (SC) beginning 24-36 hours after the last dose of chemotherapy and continuing for at least 7 days or until blood counts recover, whichever comes last. Filgrastim is discontinued at least 24 hours prior to the next course of chemotherapy.
LOCAL CONTROL: Patients who respond to induction therapy may undergo surgery alone if the lesion can be resected with negative margins and with a reasonable functional result beginning in week 13. Following surgery, patients with unresectable lesions or inadequate margins may receive radiotherapy during week 15. Patients with bulky lesions in surgically difficult sites such as the spine, skull, and periacetabular pelvis; poor response to induction chemotherapy; or those in whom surgery would result in unacceptable functional results may receive radiotherapy alone in weeks 13-19. Patients with bulky lesions in difficult sites and who do not have a good clinical and radiographic response to induction therapy may receive radiotherapy to the primary site during weeks 13-19 followed by surgery of the involved site during week 25 after recovery from course 11 of chemotherapy. Patients with microscopic residual disease after planned pre-operative radiotherapy will receive additional radiotherapy.
CONTINUATION THERAPY (WEEKS 15-36): Patients receive vincristine IV on day 1 in weeks 15, 16, 21-24, 27-30, 33, and 34; topotecan hydrochloride IV over 30 minutes on days 1-5 in weeks 15, 21, and 29; cyclophosphamide IV over 1 hour on days 1-5 in weeks 15, 21 and 29 and on day 1 in weeks 23, 27, and 33; ifosfamide IV over 1 hour on days 1-5 in weeks 17, 19, 25, 31, and 35; etoposide IV over 1 hour on days 1-5 in weeks 17, 19, 25, 31, and 35; and doxorubicin hydrochloride IV over 15 minutes on days 1 and 2 of weeks 23, 27, and 33. Patients also receive G-CSF SC as in induction therapy.
After completion of study treatment, patients are followed for 10 years.
Eligibility| Ages Eligible for Study: | up to 30 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Diagnosis of extracranial Ewing sarcoma or peripheral primitive neuroectodermal tumor of bone or soft tissue:
- Newly diagnosed disease
Disease confirmed by biopsy only with no attempt at complete or partial resection
- Unplanned excision allowed provided adequate imaging was obtained prior to surgery and incompletely resected disease is controlled by local therapy
- No esthesioneuroblastoma
Localized disease, including any of the following sites:
Chest wall tumors with ipsilateral pleural effusions, ipsilateral positive pleural fluid cytology, or ipsilateral pleural based secondary tumor nodules;
- No contralateral pleural effusions or pleural nodules
Regional lymph nodes that are clinically suspicious or confirmed by biopsy
- No distant lymph node metastases
Extra-dural tumors arising in the bony skull
- No tumors arising in the intra-dural soft tissue or the intra-dural region of the spine
No evidence of metastatic disease, defined as any of the following:
- Lesions that are discontinuous from the primary tumor
- Lesions that are not regional lymph nodes
- Lesions that do not share a body cavity with the primary tumor
No evidence by CT scan of metastatic lung disease, defined as any of the following:
One pulmonary nodule > 1 cm in diameter or more than one nodule > 0.5 cm diameter
- Pulmonary nodules that are resected and are not found to be metastatic Ewing sarcoma are allowed
Biopsy proven solitary nodules measuring 0.5 to 1.0 cm or multiple nodules measuring 0.3 to 0.5 cm
- Solitary nodules measuring < 0.5 cm or multiple nodules measuring < 0.3 cm are allowed unless biopsy proven to be metastatic (biopsy is not required)
- Karnofsky performance status (PS) 0-2 (>= 16 years old) OR Lansky PS 0-2 (< 16 years old)
Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min OR serum creatinine based on age/gender as follows:
- 1 month to < 6 months old (males and females 0.4 mg/dL)
- 6 months to < 1 year old (males and females 0.5 mg/dL)
- 1 to < 2 years old (males and females 0.6 mg/dL)
- 2 to < 6 years old (males and females 0.8 mg/dL)
- 6 to < 10 years old (males and females 1.0 mg/dL)
- 10 to < 13 years old (males and females 1.2 mg/dL)
- 13 to < 16 years old (males 1.5 mg/dL and females 1.4 mg/dL)
- >= 16 years old (males 1.7 mg/dL and females 1.4 mg/dL)
- AST or ALT < 2.5 times ULN for age
- Total bilirubin =< 1.5 times upper limit of normal (ULN) for age
- Shortening fraction of >= 27% by ECHO or ejection fraction of >= 50% by radionuclide angiogram (MUGA)
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No prior chemotherapy or radiotherapy
- No concurrent pegfilgrastim (Neulasta) or sargramostim (GM-CSF)
- No other concurrent cancer chemotherapy or immunomodulating agents, including steroids, unless used as an antiemetic
Contacts and Locations| United States, California | |
| Children's Oncology Group | |
| Arcadia, California, United States, 91006-3776 | |
| Principal Investigator: | Leo Mascarenhas | Children's Oncology Group |
More Information
No publications provided
| Responsible Party: | Children's Oncology Group |
| ClinicalTrials.gov Identifier: | NCT00618813 History of Changes |
| Other Study ID Numbers: | AEWS07P1, NCI-2009-00371, CDR0000586282, U10CA098543, COG-AEWS07P1 |
| Study First Received: | February 19, 2008 |
| Last Updated: | June 10, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Neuroectodermal Tumors Neuroectodermal Tumors, Primitive Sarcoma, Ewing's Neuroectodermal Tumors, Primitive, Peripheral Sarcoma Osteosarcoma Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Nerve Tissue Neoplasms, Neuroepithelial Neoplasms, Glandular and Epithelial Neoplasms, Bone Tissue Neoplasms, Connective Tissue Neoplasms, Connective and Soft Tissue |
Cyclophosphamide Ifosfamide Isophosphamide mustard Doxorubicin Etoposide Vincristine Topotecan Lenograstim Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Antirheumatic Agents Therapeutic Uses Antineoplastic Agents, Alkylating |
ClinicalTrials.gov processed this record on June 18, 2013