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

NCT ID: NCT01355445

Last Updated: 2019-09-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-31
• Study Completion Date: 2019-05-31

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.

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.

Conditions

RHABDOMYOSARCOMA

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Vincristine / Irinotecan

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

Group Type: ACTIVE_COMPARATOR

Vincristine, Irinotecan

Intervention Type: 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

Vincristine / Irinotecan / Temozolomide

Vincristine, Irinotecan, Temozolomide

Group Type: EXPERIMENTAL

Vincristine, Irinotecan, Temozolomide

Intervention Type: 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

Interventions

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

Intervention Type: 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

Intervention Type: DRUG

Other Intervention Names

Vincristine-Irinotecan; Vincristine-Irinotecan-Temozolomide

Eligibility 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; 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
• 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

• 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)

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

SFCE

UNKNOWN

Sponsor Role: collaborator

Centre Oscar Lambret

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anne-Sophie DEFACHELLES, MD

Role: PRINCIPAL_INVESTIGATOR

Centre Ocsar Lambret, Lille, France

Julia CHISHOLM, MD

Role: PRINCIPAL_INVESTIGATOR

Royal Marsden NHS Foundation Trust, Surrey, Uinted Kingdom

J.H.M. MD MERKS

Role: PRINCIPAL_INVESTIGATOR

Emma Children's Hospital, Amsterdam, The Netherlands

Michela CASANOVA, MD

Role: PRINCIPAL_INVESTIGATOR

Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy

Soledad GALLEGO, MDn

Role: PRINCIPAL_INVESTIGATOR

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

Locations

CHU d'Amiens Picardie Site Sud

Amiens, , France

Hôpital des Enfants, Groupe Hospitalier Pellegrin

Bordeaux, , France

Centre Oscar Lambret

Lille, , France

Centre Léon Bérard

Lyon, , France

CHU, Hôpital d'Enfants de la Timone

Marseille, , France

Hôpital Arnaud de Villeneuve - CHU

Montpellier, , France

CHU, Hôpital Mère enfants

Nantes, , France

Hôpital Armand Trousseau

Paris, , France

Institut Curie

Paris, , France

Hôpital Jean Bernard

Poitiers, , France

CHU Rennes - Hôpital Sud

Rennes, , France

CHU St Etienne - Hôpital Nord

Saint-Etienne, , France

Hôpital des enfants

Toulouse, , France

CHRU

Tours, , France

CHRU Hôpital d'Enfants

Vandœuvre-lès-Nancy, , France

Institut Gustave Roussy

Villejuif, , France

Countries

France

References

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.

Reference Type: DERIVED

PMID: 34343032 (View on PubMed)

Other Identifiers

2010-023135-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

VIT-0910

Identifier Type: -

Identifier Source: org_study_id