Overview

This trial is active, not recruiting.

Condition rhabdomyosarcoma
Treatments vincristine, irinotecan, vincristine-irinotecan-temozolomide
Phase phase 2
Sponsor Centre Oscar Lambret
Collaborator SFCE
Start date January 2012
End date June 2014
Trial size 80 participants
Trial identifier NCT01355445, 2010-023135-42, VIT-0910

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
Vincristine-Irinotecan
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 cycle / 21 days
(Experimental)
Vincristine-Irinotecan-Temozolomide
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 cycle / 21 days

Primary Outcomes

Measure
Objective tumour response and progression in each treatment arm.
time frame: at least 6 weeks (two cycles of treatment)

Secondary Outcomes

Measure
To assess the duration of tumor response in each treatment arm
time frame: During all the study
To determine the time to tumor progression in each treatment arm
time frame: During all the study
To assess the time to treatment failure in each treatment arm
time frame: Before 1 year
To assess the overall survival in each treament arm
time frame: During all the study
To assess the safety profile and tolerability in each treatment arm
time frame: During all the study

Eligibility Criteria

Male or female participants from 6 months up to 50 years old.

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)

Additional Information

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
Principal investigator Anne-Sophie DEFACHELLES, MD, International coordinator
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.
Trial information was received from ClinicalTrials.gov and was last updated in June 2014.
Information provided to ClinicalTrials.gov by Centre Oscar Lambret.