Vincristine and Irinotecan With or Without Temozolomide in Children and Adults With Refractory/Relapsed Rhabdomyosarcoma

NCT01355445 | Completed Phase 2 DMC

• 2 other identifiers: VIT-09102010-023135-42
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 16

Brief Summary

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.

Conditions

RHABDOMYOSARCOMA

Outcome Measures

Primary Outcomes (1)

• Objective tumour response and progression in each treatment arm.

  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.

  at least 6 weeks (two cycles of treatment)

Secondary Outcomes (5)

• To assess the duration of tumor response in each treatment arm

  During all the study

• To determine the time to tumor progression in each treatment arm

  During all the study

• To assess the time to treatment failure in each treatment arm

  Before 1 year

• To assess the overall survival in each treament arm

  During all the study

• To assess the safety profile and tolerability in each treatment arm

  During all the study

Study Arms (2)

Vincristine / Irinotecan

ACTIVE COMPARATOR

Vincristine, Irinotecan Vincristine :1.5 mg/m² (max 2mg), IV Irinotecan : Irinotecan 50 mg/m²/d, IV

Drug: Vincristine, Irinotecan

Vincristine / Irinotecan / Temozolomide

EXPERIMENTAL

Vincristine, Irinotecan, Temozolomide

Drug: Vincristine, Irinotecan, Temozolomide

Interventions

Vincristine, Irinotecan DRUG

* 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

Also known as: Vincristine-Irinotecan

Vincristine / Irinotecan

Vincristine, Irinotecan, Temozolomide DRUG

* 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

Also known as: Vincristine-Irinotecan-Temozolomide

Vincristine / Irinotecan / Temozolomide

Eligibility Criteria

• Age: 6 Months - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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; and ≥ 500/mm3 in case of bone marrow disease
• Platelet count ≥ 100000/mm3 ; and ≥ 75000/mm3 in case of bone marrow disease (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

You may not qualify if:

• Concomitant anti-cancer treatment
• Know hypersensitivity to any component of study drugs or ingredients
• 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)

Sponsors & Collaborators

• Centre Oscar Lambret: lead
• SFCE: collaborator

Study Sites (16)

CHU d'Amiens Picardie Site Sud

Amiens, France

Location

Hôpital des Enfants, Groupe Hospitalier Pellegrin

Bordeaux, France

Location

Centre Oscar Lambret

Lille, France

Location

Centre Léon Bérard

Lyon, France

Location

CHU, Hôpital d'Enfants de la Timone

Marseille, France

Location

Hôpital Arnaud de Villeneuve - CHU

Montpellier, France

Location

CHU, Hôpital Mère enfants

Nantes, France

Location

Hôpital Armand Trousseau

Paris, France

Location

Institut Curie

Paris, France

Location

Hôpital Jean Bernard

Poitiers, France

Location

CHU Rennes - Hôpital Sud

Rennes, France

Location

CHU St Etienne - Hôpital Nord

Saint-Etienne, France

Location

Hôpital des enfants

Toulouse, France

Location

CHRU

Tours, France

Location

CHRU Hôpital d'Enfants

Vandœuvre-lès-Nancy, France

Location

Institut Gustave Roussy

Villejuif, France

Location

Related Publications (1)

• Defachelles AS, Bogart E, Casanova M, Merks JHM, Bisogno G, Calareso G, Gallego Melcon S, Gatz SA, Le Deley MC, McHugh K, Probst A, Rocourt N, van Rijn RR, Wheatley K, Minard-Colin V, Chisholm JC. Randomized Phase II Trial of Vincristine-Irinotecan With or Without Temozolomide, in Children and Adults With Relapsed or Refractory Rhabdomyosarcoma: A European Paediatric Soft Tissue Sarcoma Study Group and Innovative Therapies for Children With Cancer Trial. J Clin Oncol. 2021 Sep 20;39(27):2979-2990. doi: 10.1200/JCO.21.00124. Epub 2021 Aug 3.

  PMID: 34343032 DERIVED

MeSH Terms

Conditions

Rhabdomyosarcoma

Interventions

Vincristine; Irinotecan; Temozolomide

Condition Hierarchy (Ancestors)

Myosarcoma; Neoplasms, Muscle Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Intervention Hierarchy (Ancestors)

Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Camptothecin; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Study Officials

• Anne-Sophie DEFACHELLES, MD

  Centre Ocsar Lambret, Lille, France

  PRINCIPAL INVESTIGATOR

• Julia CHISHOLM, MD

  Royal Marsden NHS Foundation Trust, Surrey, Uinted Kingdom

  PRINCIPAL INVESTIGATOR

• J.H.M. MD MERKS

  Emma Children's Hospital, Amsterdam, The Netherlands

  PRINCIPAL INVESTIGATOR

• Michela CASANOVA, MD

  Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy

  PRINCIPAL INVESTIGATOR

• Soledad GALLEGO, MDn

  Hospital Materno - Infantil Vall D' Hebron, Barcelona, Spain

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2011
• First Posted: May 18, 2011
• Study Start: January 1, 2012
• Primary Completion: June 1, 2018
• Study Completion: May 1, 2019
• Last Updated: September 18, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (16)