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International Randomized Phase II Trial of the Combination of Vincristine and Irinotecan With or Without Temozolomide (VI or VIT) in Children and Adults With Refractory or Relapsed Rhabdomyosarcoma

Phase 2
6 Months
50 Years
Open (Enrolling)

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Trial Information

International Randomized Phase II Trial of the Combination of Vincristine and Irinotecan With or Without Temozolomide (VI or VIT) in Children and Adults With Refractory or Relapsed Rhabdomyosarcoma

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

Inclusion Criteria:


- Histologically or cytologically confirmed diagnosis of rhabdomyosarcoma (RMS)
(new biopsy recommended)

- Relapsed or refractory disease which has failed standard treatment approaches

- Patients must have measurable disease defined as lesions that can be measured in
3 dimensions by medical imaging techniques such as CT or MRI. Ascites, pleural
fluid, bone marrow disease and lesions seen on Tc scintigraphy or PET scan only
are not considered measurable for these patients


- Age > 6 months and ≤ 50 years

- Karnofsky performance status (PS) 70-100% (for patients > 12 years of age) OR
Lansky Play Score 70-100% (for patients ≤ 12 years of age)

- Life expectancy ≥ 12 weeks

- Adequate bone marrow function :

- Absolute neutrophil count ≥ 1000/mm3

- Platelet count ≥ 100,000/mm3 (transfusion independent)

- Hemoglobin ≥ 8.5 g/dl (transfusion allowed)

- Adequate renal function

- Serum creatinine < 1.5 X ULN for age

- If serum creatinine > 1.5 ULN, creatinine clearance (or radioisotope GFR)
must be >70 ml/min/1.73 m²

- Adequate hepatic function :

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN) for age, except if
the patient is known to have Gilbert's syndrome

- ALT and AST < 2.5 times ULN for age

- Negative pregnancy test in females with childbearing potential

- Fertile patients must use effective contraception

- No active > grade 2 diarrhea or uncontrolled infection

- No other malignancy, including secondary malignancy

- Patient affiliated with a health insurance system. Applicable for French
patients only Written informed consent of patient and/or parents/guardians


- More than 3 weeks since prior radiation therapy to the site of any progressive
lesion that will be identified as a target lesion to measure tumor response

- At least 3 weeks since prior myelosuppressive therapy (6 weeks for nitrosourea.
2 weeks for vincristine, vinblastine, vinorelbine or low dose cyclophosphamide)

- No concurrent enzyme-inducing anticonvulsants (EIAC), including phenytoin,
phenobarbital or carbamazepine

- No concurrent administration of any of the following: rifampicin,
voriconazole,itraconazole, ketoconazole, aprepitant, St John's Wort

- No prior irinotecan or temozolomide administration

- Prior vincristine administration allowed

- Concurrent palliative radiation therapy to sites allowed other than the main
measurable target

- Prior allo- or autologous SCT allowed

Exclusion Criteria:

- Inclusion criteria failure

- Concomitant anti-cancer treatment

- Pregnancy or breast feeding

- Patients with rare hereditary problems of galactose intolerance, the Lapp lactase
deficiency or glucose-galactose malabsorption

- Neuromuscular disorders (e.g. Charcot-Marie Tooth disease)

- Uncontrolled intercurrent illness or active infection

- Unavailable for medical follow-up (geographic, social or psychological reasons)

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Objective tumour response and progression in each treatment arm.

Outcome Description:

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.

Outcome Time Frame:

at least 6 weeks (two cycles of treatment)

Safety Issue:


Principal Investigator

Anne-Sophie DEFACHELLES, MD, International coordinator

Investigator Role:

Principal Investigator

Investigator Affiliation:

Centre Ocsar Lambet, Lille, France


France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Study ID:




Start Date:

January 2012

Completion Date:

June 2015

Related Keywords:

  • Rhabdomyosarcoma
  • Rhabdomyosarcoma