Clinical Trial: Therapeutic Trial for Patients With Ewing Sarcoma Family of Tumor and Desmoplastic Small Round Cell Tumors

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Therapeutic Trial for Patients With Ewing Sarcoma Family of Tumor and Desmoplastic Small Round Cell Tumors

Brief Summary:

This protocol will study treatment for Ewing sarcoma family of tumors (ESFT) and desmoplastic small round cell tumor (DSRCT). Participants with ESFT will be divided into two treatment groups, A or B, based on tumor characteristics.

Group A (standard risk) participants have tumor that is not in the pelvis, has not spread to other parts of the body, and are less than 14 years of age. Because previous clinical trials have shown that standard treatment is very effective for children whose tumors have these characteristics, these participants will receive standard treatment.

Group B (high risk) participants are 14 years of age or older or have tumor in the pelvis, or the tumor has spread to other parts of the body. Participants with DSRCT in the abdomen and/or pelvis or with tumor that cannot be removed by surgery alone or has spread to other parts of the body will be included in Group B. Participants in this group are considered high risk because there is a greater chance of tumor recurring following standard treatments currently in use.

All participants will be followed and evaluated for 10 years following completion of therapy.


Detailed Summary:

PRIMARY OBJECTIVE:

  • To estimate the response rate to two initial courses of temsirolimus, temozolomide and irinotecan in previously untreated patients with high-risk Ewing sarcoma family of tumors (ESFT).

SECONDARY OBJECTIVES:

  • To estimate the overall survival and progression-free survival in participants with ESFT treated with these approaches.
  • To estimate the time to progression in participants with ESFT treated in Group B (high risk).
  • To estimate the cumulative incidence of local failure following local control paradigm in this trial.

Group A:

Participants will receive interval compressed (every 2 weeks) alternating courses of chemotherapy with vincristine, doxorubicin, and cyclophosphamide (VDC) and with ifosfamide and etoposide (IE). Doxorubicin will be omitted following a total cumulative dose of 375 mg/m^2. Local control measures (surgery and/or radiation therapy) will be instituted after 6 courses of chemotherapy. Total duration of treatment is approximately 29 weeks.

Group B:

Participants eligible for the window therapy will receive two courses (21 days duration each) of mTOR inhibitor, temsirolimus, in combination with temozolomide and irinotecan. Irinotecan (20 mg/m^2) will be administered IV on a protracted schedule of daily for 5 days, 2 days off, repeated daily x 5 [(qdx5)x2], temozolomide (100 mg/m^2) PO daily x 5 days and temsirolimus 35 mg/m^2 IV weekly on day 1 and 8. Following window treatment (weeks 1 - 6), partici
Sponsor: St. Jude Children's Research Hospital

Current Primary Outcome: Response to Window Therapy (2 Courses) for Group B (High-risk) - ESFT Participants [ Time Frame: at 6 weeks after start of therapy (after 2 initial courses) ]

Response rate will be defined as the proportion of patients who achieved complete response or partial response (CR+PR) using the World Health Organization (WHO) criteria evaluated after two initial courses of temsirolimus, temozolomide and irinotecan in previously untreated patients with high risk Ewing Sarcoma Family of Tumor (ESFT). Participants who are treated in Group B with Desmoplastic Small Round Cell Tumor (DSRCT) or those who do not receive window therapy will not be included in this analysis.


Original Primary Outcome: Response rate [ Time Frame: at 6 weeks after start of therapy (after 2 initial courses) ]

Response rate will be defined as the proportion of patients who achieved complete response or partial response (CR+PR) using the World Health Organization (WHO) criteria evaluated after two initial courses of temsirolimus, temozolomide and irinotecan in previously untreated patients with high risk ESFT. Participants who are treated in Group B with DSRCT or those who do not receive window therapy will not be included in this analysis.


Current Secondary Outcome:

  • Overall Survival [ Time Frame: Maximum of 11 years after the start of therapy ]
    Overall survival (OS) is defined as the time interval from the date on study to the date of death or the date of last follow-up. OS will be estimated using the method of Kaplan-Meier for group A and B participants, respectively.
  • Progression-free Survival [ Time Frame: Maximum of 11 years after the start of therapy ]
    Progression free survival (PFS) is defined as the time interval from the date on study to the date of disease progression or death or the date if last follow-up. PFS will be estimated using the method of Kaplan-Meier for group A and B participants, respectively.
  • Time to Progression [ Time Frame: Maximum of 11 years after the start of therapy ]
    Median time to progression of group B patients will be estimated from the Kaplan-Meier curve.
  • Local Failure Rate [ Time Frame: Maximum of 11 years after the start of therapy ]
    Loco-regional failure is defined as the time interval from date of start of local therapy to date of loco-regional failure. Distant failure or death prior to loco-regional failure will be considered competing events in the analyses. The cumulative incidence of loco-regional failure will be estimated using methods described in Kalbfleisch and Prentice.


Original Secondary Outcome: Same as current

Information By: St. Jude Children's Research Hospital

Dates:
Date Received: September 16, 2013
Date Started: November 2013
Date Completion: July 2026
Last Updated: August 25, 2016
Last Verified: August 2016