Clinical Trial: Combination Chemotherapy With or Without Temsirolimus in Treating Patients With Intermediate Risk Rhabdomyosarcoma

Study Status: Suspended
Recruit Status: Suspended
Study Type: Interventional

Official Title: A Randomized Phase 3 Study of Vincristine, Dactinomycin, Cyclophosphamide (VAC) Alternating With Vincristine and Irinotecan (VI) Versus VAC/VI Plus Temsirolimus (TORI, Torisel, NSC# 683864, IND#122782

Brief Summary: This randomized phase III trial studies how well combination chemotherapy (vincristine sulfate, dactinomycin, cyclophosphamide alternated with vincristine sulfate and irinotecan hydrochloride) works compared to combination chemotherapy plus temsirolimus in treating patients with rhabdomyosarcoma (cancer that forms in the soft tissues, such as muscle), and has an intermediate chance of coming back after treatment (intermediate risk). Drugs used in chemotherapy 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. Combination chemotherapy and temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether combination chemotherapy or combination chemotherapy plus temsirolimus is more effective in treating patients with intermediate-risk rhabdomyosarcoma.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To compare the event-free survival (EFS) of patients with intermediate-risk (IR) rhabdomyosarcoma (RMS) treated with surgery, radiotherapy, and vincristine (vincristine sulfate), dactinomycin, and cyclophosphamide (VAC) alternating with vincristine and irinotecan (irinotecan hydrochloride) (VI) (VAC/VI) to that of patients treated with surgery, radiotherapy and VAC/VI plus temsirolimus (TORI).

SECONDARY OBJECTIVES:

I. To compare the overall survival (OS) of patients with IR RMS treated with surgery, radiotherapy, and VAC alternating with VI to that of patients treated with surgery, radiotherapy and VAC/VI plus TORI.

TERTIARY OBJECTIVES:

I. To compare the outcome of patients based on their forkhead box O1 protein (FOXO1) fusion gene partner, by evaluating paired box (PAX) 3 vs PAX7 in all patients found to be FOXO1 fusion positive.

II. To compare the outcome of patients based on their [F18]-fluorodeoxy-D-glucose-positron emission tomography (FDG-PET) response at week 9 (positive or negative), as assessed by Deauville criteria (5-point).

OUTLINE:

FEASIBILITY PHASE: (< 21 years old): This is a dose-escalation study of temsirolimus.

Patients receive vincristine sulfate intravenously (IV) over 1 minute on day 1 of weeks 1-13, 16, 17, 19, 20, 22-26, 28, 31-34, 37, 38, and 40, dactinomycin IV over 1-5 minutes on day 1 of weeks 1, 7, 13, 22, 28, 34, and 40, cyclophosphamide IV over 60 minutes on day 1 of weeks 1, 7, 13, 22, 28, 34, and 40, irinotecan hydrochlori
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: EFS [ Time Frame: Time from study enrollment to the first occurrence of progression, relapse, second malignant neoplasm or death as a first event ]

EFS distributions will be estimated using the Kaplan-Meier method and will be compared between the randomized treatment groups using the log-rank test.


Original Primary Outcome:

  • EFS [ Time Frame: Time from study enrollment to death from any cause, assessed up to 10 years ]
    EFS distributions will be estimated using the Kaplan-Meier method and will be compared between the randomized treatment groups using the log-rank test.
  • Incidence of adverse events with addition of TORI with VAC/VI (Feasibility phase) using Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to week 12 ]


Current Secondary Outcome: OS [ Time Frame: Time from study enrollment to death from any cause, assessed up to 10 years ]

OS distributions will be estimated using the Kaplan-Meier method and will be compared between the randomized treatment groups using the log-rank test.


Original Secondary Outcome:

  • Bladder function as self-reported by patient/parent using a 14 point questionnaire [ Time Frame: Up to 6 years ]
  • OS [ Time Frame: Time from study enrollment to death from any cause, assessed up to 10 years ]
    OS distributions will be estimated using the Kaplan-Meier method and will be compared between the randomized treatment groups using the log-rank test.
  • Self-reported nausea sub-score as measured by PedsQL 3.0 [ Time Frame: Up to 3 months after completion of study treatment ]
  • Self-reported pain sub score as measured by PedsQL 3.0 [ Time Frame: Up to 3 months after completion of study treatment ]
  • Self-reported physical functioning summary score using Pediatric Quality of Life (PedsQL) 4.0 Generic Core Scales [ Time Frame: Up to 3 months after completion of study treatment ]
    Compared between patients receiving VAC/VI versus VAC/VI plus TORI.


Information By: National Cancer Institute (NCI)

Dates:
Date Received: October 2, 2015
Date Started: May 2016
Date Completion:
Last Updated: May 19, 2017
Last Verified: May 2017