Protocol Summary

Protocol No.: OCR14009

Sponsor Protocol No.: AEWS1221

Protocol Title: Combination Chemotherapy With or Without Ganitumab in Treating Patients With Newly Diagnosed Metastatic Ewing Sarcoma

Principal Investigator: Slayton, William

Objective: This randomized phase II trial studies how well combination chemotherapy with or without ganitumab works in treating patients with newly diagnosed Ewing sarcoma that has spread to other parts of the body. Monoclonal antibodies, such as ganitumab, may block tumor growth in different ways by targeting certain cells. Drugs used in chemotherapy, such as vincristine sulfate, doxorubicin hydrochloride, cyclophosphamide, ifosfamide, and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether combination chemotherapy is more effective with or without ganitumab in treating patients with newly diagnosed Ewing sarcoma.

Description: Participants will be randomized to receive either chemotherapy with Ganitumab or chemotherapy alone. Arm A: INDUCTION THERAPY: Patients receive vincristine sulfate IV over 1 minute on day 1; doxorubicin hydrochloride IV over 1-15 minutes on days 1 and 2; and cyclophosphamide IV over 30-60 minutes on day 1 of weeks 1, 5, and 9; and ifosfamide IV over 1 hour on days 1 to 5 and etoposide IV over 1-2 hours on days 1 to 5 of weeks 3, 7, and 11. LOCAL CONTROL THERAPY: Between weeks 13-18, patients undergo surgery and/or radiation therapy. CONSOLIDATION THERAPY: Patients receive vincristine sulfate IV over 1 minute on day 1 of weeks 1, 7, 9, and 13; doxorubicin hydrochloride IV over 1-15 minutes on days 1 and 2 of weeks 1 and 7; cyclophosphamide IV over 30-60 minutes on day 1 of weeks 1, 7, 9, and 13; ifosfamide IV over 1 hour on days 1 to 5 of weeks 3, 5, 11, and 15; and etoposide IV over 1-2 hours on days 1 to 5 of weeks 3, 5, 11, and 15. METASTATIC SITE IRRADIATION: Patients with lung metastases undergo definitive SBRT or EBRT over 5 days. Arm B: INDUCTION THERAPY: Patients receive Induction therapy as in Regimen A and receive ganitumab IV over 30-60 minutes or 60-120 minutes on day 1 of weeks 1, 3, 5, 7, 9, and 11. LOCAL CONTROL THERAPY: Between weeks 13-18, patients undergo surgery and/or radiation therapy. CONSOLIDATION THERAPY: Patients receive Consolidation therapy as in Regimen A and ganitumab IV over 30-60 minutes or 60-120 minutes on day 1 of weeks 7, 9, 11, 13, and 15. METASTATIC SITE IRRADIATION: Patients with lung metastases undergo definitive SBRT or EBRT over 5 days. MAINTENANCE THERAPY: Patients receive ganitumab IV over 30-60 minutes or 60-120 minutes on day 1 in weeks 1, 4, 7, 10, 13, 16, 19, and 22.

Phase: Phase III

Age Group: Both

Age: N/A - 50 Years

Gender: All

Scope: National

Treatment:
Arm A: VDC/IE
Arm B: VDC/IE + ganitumab

Detailed Eligibility:
Inclusion Criteria:
1. Ages up to 50 years old
2. Patients with histologic diagnosis (by institutional pathologist) of newly diagnosed Ewing sarcoma or peripheral primitive neuroectodermal tumor (PNET) arising from bone or soft tissue and with metastatic disease involving lung, bone, bone marrow, or other metastatic site
3. The planned biology studies are critical for the success of this clinical trial; therefore, submission of pre-treatment serum, pre-treatment paraffin-embedded tumor material and pre-treatment whole blood is mandatory for enrollment; failure to submit the mandatory baseline serum, whole blood, and tumor material within 4 weeks of study enrollment will result in the patient being declared ineligible and such patients will be removed from protocol therapy and go off study
4. Patients should only have had a biopsy of the primary tumor without an attempt at complete or partial resection; patients will still be eligible if excision was attempted or accomplished as long as adequate anatomic imaging (MRI for most primary tumor sites) was obtained prior to surgery
5. Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or a serum creatinine based on age/gender
6. Total bilirubin =7. Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) 8. Shortening fraction of >= 27% by echocardiogram, or
9. Ejection fraction of >= 50% by radionuclide study
10. Patients must have a normal blood sugar level for age to participate; if an initial random draw (ie. non-fasting) blood glucose value is out of range, it is acceptable to repeat this test as a fasting draw
Exclusion Criteria:
1. Patients with regional node involvement as their only site of disease beyond the primary tumor will not be eligible
2. Patients whose primary tumors arise in the intra-dural soft tissue (eg. brain and spinal cord) are not eligible
3. Patients who have received prior chemotherapy or radiation therapy are not eligible
4. Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained; lactating females are not eligible unless they have agreed not to breastfeed their infants for the duration of protocol therapy; sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of protocol therapy
5. Patients with known pre-existing diabetes mellitus will be excluded from study
6. Patients receiving chronic pharmacologic doses of corticosteroids are not eligible; patients receiving chronic inhaled corticosteroids or chronic physiologic replacement doses of corticosteroids are eligible

Applicable Conditions:

  • Brain and Nervous System
  • Pediatric (Childhood) Cancer
  • Sarcoma
  • Participation Institution:

  • UF Gainesville : Ashley Bayne
  • UF Jacksonville : Ashley Bayne
  • Contact:
    Ashley Bayne, RN
    Phone: +1 352-294-8745
    Email: abayne@ufl.edu

    More Information: View study listing on ClinicialTrials.gov http://www.clinicaltrials.gov/ct2/show/NCT02306161