Vincristine and Irinotecan With or Without Temozolomide in Children and Adults With Refractory or Relapsed Rhabdomyosarcoma : International Randomized Trial (VIT-0910)

• Objective tumour response and progression in each treatment arm. [ Time Frame: at least 6 weeks (two cycles of treatment) ] [ Designated as safety issue: No ]
  The primary efficacy endpoint is defined as the proportion of patients who had a documented complete or partial tumour response occurring after the first 2 cycles of treatment which must be confirmed by a follow-up objective tumour assessment obtained within 4-5 weeks after the initial documentation.
  
  

• To assess the duration of tumor response in each treatment arm [ Time Frame: During all the study ] [ Designated as safety issue: No ]
  The duration of tumour response is defined as the time from first documentation of objective tumour response to the first objective or clinical documentation of progression
  
  
• To determine the time to tumor progression in each treatment arm [ Time Frame: During all the study ] [ Designated as safety issue: No ]
  The time to tumor progression: the time from the date of first treatment administration to the date of first objective or clinical documentation of tumour progression or death due to any cause
  
  
• To assess the time to treatment failure in each treatment arm [ Time Frame: Before 1 year ] [ Designated as safety issue: No ]
  The time to treatment failure is defined as the time from the date of first treatment administration to the first documentation of tumour progression, discontinuation of study treatment before one year, or death, whichever occurs first
  
  
• To assess the overall survival in each treament arm [ Time Frame: During all the study ] [ Designated as safety issue: No ]
  The overall survival is defined as the time from the date of first treatment administration to date of death
  
  
• To assess the safety profile and tolerability in each treatment arm [ Time Frame: During all the study ] [ Designated as safety issue: Yes ]

  Safety parameters include adverse events and haematology and blood chemistry assays.

  Safety evaluations will include characterization of the frequency and severity of adverse events, complete blood cell counts with differential, serum chemistries and electrolytes, and change in weight and body surface area (BSA).

  
  

The dose of vincristine will be 1.5 mg/m² or 0.05 mg/kg for patient ≤ 10 kg (maximum 2 mg) and will be administered by direct intravenous infusion on day 1 and 8 of each course, before irinotecan.

The dose of irinotecan will be 50 mg/m²/d. Irinotecan will be given intravenously over 1 hour on days 1-5 of each course, one hour following the administration of temozolomide.

In the absence of any contraindication (ie known allergies), treatment with oral cefixime 8 mg/kg once daily (maximum daily dose 400 mg) is recommended and will be started 2 days before chemotherapy until day 7.

Temozolomide will be given according to the randomization. The starting dose of temozolomide will be 125 mg/m²/d. The dose of temozolomide will be escalated to 150 mg/m²/day at cycle 2 for patients who do not experience > grade 3 toxicity of any kind. Temozolomide will be given orally, on an empty stomach, on days 1 through 5 of each course.

Dose reductions and/or administration delays will be performed using specific predefined rules to accommodate individual patient tolerance of treatment and to maintain optimal dose intensity.