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Vincristine and Irinotecan With or Without Temozolomide in Children and Adults With Refractory/Relapsed Rhabdomyosarcoma (VIT-0910)

Primary Purpose

RHABDOMYOSARCOMA

Status

Completed

Phase

Phase 2

Locations

France

Study Type

Interventional

Intervention

Vincristine, Irinotecan

Vincristine, Irinotecan, Temozolomide

About this trial

This is an interventional treatment trial for RHABDOMYOSARCOMA

Eligibility Criteria

6 Months - 50 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Exclusion Criteria:

Inclusion criteria failure
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)

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Vincristine / Irinotecan

Vincristine / Irinotecan / Temozolomide

Arm Description

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

Vincristine, Irinotecan, Temozolomide

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

To assess the duration of tumor response in each treatment arm

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

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

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

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

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).

Full Information

NCT ID

NCT01355445

First Posted

May 16, 2011

Last Updated

September 17, 2019

Sponsor

Centre Oscar Lambret

Collaborators

SFCE

1. Study Identification

Unique Protocol Identification Number

NCT01355445

Brief Title

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

Acronym

VIT-0910

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2019

Overall Recruitment Status

Completed

Study Start Date

January 2012 (Actual)

Primary Completion Date

June 2018 (Actual)

Study Completion Date

May 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Centre Oscar Lambret

Collaborators

SFCE

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

RHABDOMYOSARCOMA

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

120 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Vincristine / Irinotecan

Arm Type

Active Comparator

Arm Description

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

Arm Title

Vincristine / Irinotecan / Temozolomide

Arm Type

Experimental

Arm Description

Vincristine, Irinotecan, Temozolomide

Intervention Type

Drug

Intervention Name(s)

Vincristine, Irinotecan

Other Intervention Name(s)

Vincristine-Irinotecan

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Vincristine, Irinotecan, Temozolomide

Other Intervention Name(s)

Vincristine-Irinotecan-Temozolomide

Intervention Description

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 Outcome Measure Information:

Title

Objective tumour response and progression in each treatment arm.

Description

Time Frame

at least 6 weeks (two cycles of treatment)

Secondary Outcome Measure Information:

Title

To assess the duration of tumor response in each treatment arm

Description

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

Time Frame

During all the study

Title

To determine the time to tumor progression in each treatment arm

Description

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

Time Frame

During all the study

Title

To assess the time to treatment failure in each treatment arm

Description

Time Frame

Before 1 year

Title

To assess the overall survival in each treament arm

Description

The overall survival is defined as the time from the date of first treatment administration to date of death

Time Frame

During all the study

Title

To assess the safety profile and tolerability in each treatment arm

Description

Time Frame

During all the study

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Months

Maximum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

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 Exclusion Criteria: Inclusion criteria failure 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)

Overall Study Officials: