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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
SFCE
Information provided by (Responsible Party):
Centre Oscar Lambret
ClinicalTrials.gov Identifier:
NCT01355445
First received: May 16, 2011
Last updated: June 20, 2014
Last verified: June 2014
  Purpose

This is an international open-label, randomized, multicenter phase II study of VIT and VI for the treatment of patients with recurrent or refractory rhabdomyosarcoma. The study will evaluate the safety and efficacy of these combinations in patients with recurrent or refractory rhabdomyosarcoma.


Condition Intervention Phase
RHABDOMYOSARCOMA
Drug: Vincristine, Irinotecan
Drug: Vincristine-Irinotecan-Temozolomide
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Centre Oscar Lambret:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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).



Estimated Enrollment: 80
Study Start Date: January 2012
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: VI
Vincristine-Irinotecan
Drug: Vincristine, Irinotecan
  • D1 and D8: Vincristine 1.5 mg/m² (max 2mg) direct IV infusion (0.05 mg/kg for patient ≤ 10 kg)
  • D1 to D5: Irinotecan 50 mg/m²/d, IV

    1. cycle / 21 days
Experimental: VIT
Vincristine-Irinotecan-Temozolomide
Drug: Vincristine-Irinotecan-Temozolomide
  • D1 to D5: Temozolomide 125 mg/m²/d, PO (the dose will be escalated to 150 mg/m²/day at cycle 2 for patients who do not experience > grade 3 toxicity of any kind)
  • D1 and D8: Vincristine 1.5 mg/m² (maximum 2mg) direct IV infusion (0.05 mg/kg for patient ≤ 10 kg)
  • D1 to D5: Irinotecan 50 mg/m²/d, IV

    1. cycle / 21 days

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   6 Months to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • TUMOR CHARACTERISTICS :

    • 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
  • PATIENT CHARACTERISTICS :

    • 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
  • PRIOR or CONCURRENT THERAPY :

    • 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01355445

Locations
France
Centre Hospitalier Universitaire Nord
Amiens, France, 80000
CHU
Angers, France, 49000
Hôpital des Enfants, Groupe Hospitalier Pellegrin
Bordeaux, France, 33076
CHU Estaing
Clermont ferrand, France, 63003
Clinique Médicale de Pédiatrie - CHU
Grenoble, France, 38043
Centre Oscar Lambret
Lille cedex, France, 59020
Centre Léon Bérard
Lyon, France, 69373
CHU, Hôpital d'Enfants de la Timone
Marseille, France, 13385
Hôpital Arnaud de Villeneuve - CHU
Montpellier, France, 34295
CHU, Hôpital Mère enfants
Nantes, France, 44000
Hôpital Armand Trousseau
Paris, France, 75012
Institut Curie
Paris, France, 75231
Hôpital Jean Bernard
Poitiers, France, 86021
CHU - Hôpital Américain
Reims, France, 51100
CHU Rennes - Hôpital Sud
Rennes, France, 35203
Hôpital de Hautepierre
Strasbourg, France, 67098
CHU St Etienne - Hôpital Nord
Sy Priest en Jarez, France, 42055
Hôpital des enfants
Toulouse, France, 31059
CHRU
Tours, France, 37044
CHRU Hôpital d'Enfants
Vandoeuvre les Nancy, France, 54511
Institut Gustave-Roussy
Villejuif, France, 94800
Sponsors and Collaborators
Centre Oscar Lambret
SFCE
Investigators
Principal Investigator: Anne-Sophie DEFACHELLES, MD, International coordinator Centre Ocsar Lambet, Lille, France
Principal Investigator: Julia CHISHOLM, MD, coordinator Royal Marsden NHS Foundation Trust, Surrey, Uinted Kingdom
Principal Investigator: J.H.M. MD MERKS, Coordinator Emma Children's Hospital, Amsterdam, The Netherlands
Principal Investigator: Michela CASANOVA, MD, coordinator Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy
Principal Investigator: Soledad GALLEGO, MDn coordinator Hospital Materno - Infantil Vall D' Hebron, Barcelona, Spain
  More Information

No publications provided

Responsible Party: Centre Oscar Lambret
ClinicalTrials.gov Identifier: NCT01355445     History of Changes
Other Study ID Numbers: VIT-0910, 2010-023135-42
Study First Received: May 16, 2011
Last Updated: June 20, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Italy: Local CA
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Spain: AEMPS

Additional relevant MeSH terms:
Rhabdomyosarcoma
Myosarcoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Connective and Soft Tissue
Neoplasms, Muscle Tissue
Sarcoma
Camptothecin
Dacarbazine
Irinotecan
Temozolomide
Vincristine
Alkylating Agents
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Radiation-Sensitizing Agents
Therapeutic Uses
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Tubulin Modulators

ClinicalTrials.gov processed this record on November 20, 2014