Vinblastine, Celecoxib, and Combination Chemotherapy in Treating Patients With Newly-Diagnosed Metastatic Ewing's Sarcoma Family of Tumors

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00061893
First received: June 5, 2003
Last updated: September 16, 2014
Last verified: September 2014
  Purpose

RATIONALE: Drugs used in chemotherapy, such as vinblastine, work in different ways to stop tumor cells from dividing so they stop growing or die. Celecoxib may stop the growth of Ewing's sarcoma by stopping blood flow to the tumor. Combining more than one chemotherapy drug with celecoxib may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combining low-dose vinblastine and celecoxib with standard regimens of combination chemotherapy in treating patients who have newly-diagnosed metastatic Ewing's sarcoma family of tumors.


Condition Intervention Phase
Sarcoma
Drug: celecoxib
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: etoposide
Drug: ifosfamide
Drug: vinblastine sulfate
Drug: vincristine sulfate
Procedure: conventional surgery
Radiation: radiation therapy
Drug: MESNA
Drug: Filgrastim
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Occurrence of Severe Toxicity [ Time Frame: The first two cycles (6 weeks) of protocol chemotherapy ] [ Designated as safety issue: Yes ]
    An incidence of severe toxicity is defined to be the occurrence of grade 3 or higher infection or grade 3 or higher sensory neuropathy during cycles 1-2 of protocol therapy. If 12 or more patients experience grade 3 or higher infection or five or more patients experience grade 3 or higher sensory neuropathy during cycles 1-2 of protocol therapy, the regimen will be flagged as being associated with an excessive rate of severe toxicity.


Secondary Outcome Measures:
  • Event Free Survival [ Time Frame: 24 months after start of protocol therapy ] [ Designated as safety issue: No ]

Enrollment: 38
Study Start Date: April 2004
Study Completion Date: December 2013
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Combination chemotherapy
Metastatic Ewing Sarcoma - 14-cycle study building on conventional tx (cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, ifosfamide, etoposide) and adding two antiangiogenic agents: the vinca alkaloid vinblastine and the cyclooxygenase-2 inhibitor celecoxib. Refer to the Interventions section for dosages, method of delivery and frequency of administration.
Drug: celecoxib
Given orally, Celecoxib 250 mg/m2 PO BID (500mg/m2/day) from Day 1 of Cycle 1 through Day 21 of Cycle 14. The dose should be rounded off to the nearest 100 mg. If PK studies are being done, Celecoxib should be given 24 hours prior to the other drugs for Cycle 1 only. [Celecoxib may be interrupted for up to 7 days around the time of surgical procedures.] .
Drug: cyclophosphamide
Given IV, 1200 mg/m2 IV infusion over 1 hour with MESNA uroprotection, on Day 1. For children < 1 year treat with 50% doses calculated on a m2 basis. If tolerated (no delay in administration of the next cycle due to delayed count recovery or delayed resolution of other toxicities and no serious toxicities), consider increasing to 75% and then to 100% of the calculated full dose.
Drug: doxorubicin hydrochloride
Given IV, Doxorubicin 75 mg/ m2 /course continuous IV infusion over 48 hours, beginning Day 1. Note: The total doxorubicin dose per cycle is 75 mg/ m2, which will be given as 37.5 mg/m2/day x 2 days. Doxorubicin may be given as a continuous infusion or brief infusion.
Drug: etoposide
Given IV, Vincristine 2 mg/m2 IV push, on Day 1. Maximum dose 2 mg. For children < 1 year treat with 50% doses calculated on a m2 basis. If tolerated (no delay in administration of the next cycle due to delayed count recovery or delayed resolution of other toxicities and no serious toxicities), consider increasing to 75% and then to 100% of the calculated full dose.
Drug: ifosfamide
Given IV,Ifosfamide 1800 mg/m2 /day IV infusion over 1 hour, Days 1-5 of each cycle. (9,000 mg/m2 max total dose per cycle). Prehydrate for 6 hours, 1,000 ml/m2 total volume (165 ml/m2/hour for 6 hours). For children < 1 year treat with 50% doses calculated on a m2 basis. If tolerated (no delay in administration of the next cycle due to delayed count recovery or delayed resolution of other toxicities and no serious toxicities), consider increasing to 75% and then to 100% of the calculated full dose.
Drug: vinblastine sulfate
Given IV, Vinblastine 1 mg/m2/d IV push three times per week beginning Day 1 of Cycle 1 and continuing through Day 21 of Cycle 14. In weeks during which vincristine is given, hold one dose of vinblastine and administer only 2 doses of vinblastine during that week. If vinblastine is due the same day as vincristine, hold that dose of vinblastine. [Vinblastine may be interrupted for up to 7 days around the time of surgical procedures.]
Drug: vincristine sulfate
Given IV, Vincristine 2 mg/m2 IV push, on Day 1. Maximum dose 2 mg. For children < 1 year treat with 50% doses calculated on a m2 basis. If tolerated (no delay in administration of the next cycle due to delayed count recovery or delayed resolution of other toxicities and no serious toxicities), consider increasing to 75% and then to 100% of the calculated full dose.
Procedure: conventional surgery
Patients who respond to induction chemotherapy undergo surgery on week 13. Patients who have inadequate margins after surgery undergo radiotherapy beginning on week 15. (see Detailed Description for frequency of administration and groups evaluated)
Radiation: radiation therapy
Patients with unresectable lesions undergo radiotherapy 5 days a week for approximately 6 weeks beginning on week 13. (see Detailed Description for frequency of administration and groups evaluated)
Drug: MESNA
The total daily MESNA dose is equal to at least 60% of the daily cyclophosphamide or ifosfamide dose, or by continuous infusion of the 60% dose. MESNA continuous infusion should be started at the same time as the cyclophosphamide/ifosfamide and be completed no sooner than 8 hours after the end of the cyclophosphamide or ifosfamide infusion. The oral dose of MESNA is 2x the IV dose. Patients able to tolerate oral MESNA may receive the final dose by mouth at 40% of the oxazaphosphorine (cyclophosphamide or ifosfamide) dose. The dose should be given two hours earlier than the IV dose would be given. Additionally, if the patient vomits within two hours after the oral dose, the dose should be repeated or IV MESNA given.
Drug: Filgrastim
G-CSF (Filgrastim) 5 micrograms/kg/day subcutaneously beginning 24 to 48 hours after the last dose of chemotherapy, and continuing until the absolute neutrophil count is 2,000/µL or greater after nadir.
Other Name: G-CSF

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   up to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

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

  • Not specified

Hematopoietic

  • Not specified

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 m^2
  • No allergy to sulfa
  • No aspirin hypersensitivity
  • No asthma triad (asthma with nasal polyps, and urticaria)
  • No other prior cancer, including nonmelanoma skin cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No prior bone marrow or stem cell transplantation

Chemotherapy

  • No prior chemotherapy

Endocrine therapy

  • Not specified

Radiotherapy

  • No prior radiotherapy

Surgery

  • Not specified

Other

  • No other concurrent nonsteroidal anti-inflammatory medications, including salicylates
  • No concurrent dexrazoxane unless approved by the study investigator
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00061893

  Show 101 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Judy L. Felgenhauer, MD, PS Sacred Heart Children's Hospital
  More Information

Additional Information:
Publications:
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00061893     History of Changes
Other Study ID Numbers: AEWS02P1, CDR0000302409
Study First Received: June 5, 2003
Results First Received: January 17, 2013
Last Updated: September 16, 2014
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor

Additional relevant MeSH terms:
Sarcoma
Sarcoma, Ewing
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Osteosarcoma
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Cyclophosphamide
Celecoxib
Ifosfamide
Isophosphamide mustard
Liposomal doxorubicin
Doxorubicin
Etoposide
Vincristine
Vinblastine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors

ClinicalTrials.gov processed this record on October 01, 2014