Combination Chemotherapy in Treating Children With Metastatic Rhabdomyosarcoma or Other Malignant Mesenchymal Tumors

Ovarian Cancer Clinical Trial

Official title:

MMT 98 Study For Metastatic Disease Rhabdomyosarcoma And Other Malignant Soft Tissue Sarcoma Of Childhood

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00025441
• Other study ID #: CDR0000068961
• Secondary ID: SIOP-MMT-98SFOP-
• Status: Completed
• Phase: Phase 2
• First received: October 11, 2001
• Last updated: December 3, 2013
• Start date: November 1998
• Est. completion date: March 2010

Study information

• Verified date: November 2001
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy in treating children with metastatic rhabdomyosarcoma or other malignant mesenchymal tumors.

Description:

OBJECTIVES:

• Determine the overall survival of children with metastatic rhabdomyosarcoma or other malignant mesenchymal tumors treated with one of two different chemotherapy regimens based upon risk group.

• Determine the role of low-intensity maintenance chemotherapy after intensive conventional chemotherapy in standard-risk children.

• Determine the value of a therapeutic window in high-risk children.

• Determine the role of sequential high-dose chemotherapy with peripheral blood stem cell transplantation in achieving complete response in high-risk children.

• Determine the complete response, overall survival, and event-free survival in high-risk children.

OUTLINE: This is a multicenter study. Patients are stratified according to risk group (standard vs high).

Standard-risk patients:

• Initial chemotherapy: Patients receive vincristine IV on day 1 for weeks 1-7. Patients also receive dactinomycin IV on day 1 and ifosfamide IV over 1 hour on days 1-3 of week

1. Patients then receive carboplatin IV over 1 hour and epirubicin IV over 6 hours on day 1 of week 4. Patients then receive ifosfamide IV over 1 hour and etoposide IV over 4 hours on days 1-3 of week 7. Treatment repeats every 8 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. After the second course, patients with less than 50% partial response (PR) are removed from study.

Patients with parameningeal disease undergo radiotherapy 5 days a week for about 8 weeks beginning at week 9.

• Maintenance chemotherapy: Patients receive cyclophosphamide IV over 1 hour, vincristine IV, and dactinomycin IV on day 1. Treatment repeats every 3 weeks for 9 courses in the absence of disease progression or unacceptable toxicity.

Patients who remain in PR at week 17 undergo radiotherapy for about 9 weeks beginning at week 18.

High-risk patients:

• Initial chemotherapy: Patients receive window study drug carboplatin IV over 1 hour or doxorubicin on day 1. Treatment repeats every 3 weeks for 2 courses.

Patients receive high-dose cyclophosphamide IV over 1 hour on days 1-3 of week 7. Beginning on day 8, patients receive filgrastim (G-CSF) IV or subcutaneously (SC) daily until day 13. Patients may undergo peripheral blood stem cell (PBSC) collection.

Patients receive high-dose etoposide IV over 24 hours on days 15-17. Beginning on day 22, patients receive G-CSF IV or SC daily until day 27.

Patients receive high-dose cyclophosphamide IV over 1 hour on days 29-31. Beginning on day 36, patients receive G-CSF IV or SC daily until day 42. Patients may undergo PBSC collection if not previously performed. Patients who achieve complete response (CR) are removed from study.

Patients receive high-dose carboplatin IV over 1 hour on days 44-48. Patients undergo PBSC reinfusion on day 52. Beginning on day 55, patients receive G-CSF IV or SC daily until blood counts recover.

• Maintenance chemotherapy: Patients receive maintenance chemotherapy comprising cyclophosphamide, vincristine, and dactinomycin in the same manner as the standard-risk patients.

Patients with parameningeal disease and those not achieving CR undergo radiotherapy beginning at week 17. Patients achieving CR, unless metastatic disease is resected, undergo radiotherapy beginning on week 15.

Patients are followed every 2 months for 2 years, every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 8-30 standard-risk patients will be accrued for this study within 4 years. A total of 15-75 high-risk patients will be accrued for this study within 4-5 years.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: March 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 6 Years to 17 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed metastatic rhabdomyosarcoma or other malignant mesenchymal tumors

• Standard risk defined as:

• Less than 10 years of age

• No bone or bone marrow involvement

• High risk defined as:

• At least 10 years of age OR

• Bone or bone marrow involvement

• Diagnosed less than 8 weeks ago

• Previously untreated disease except for initial surgery within the past 8 weeks

PATIENT CHARACTERISTICS:

Age:

• 6 months to under 18 years

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No prior biologic therapy

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• No prior endocrine therapy

Radiotherapy:

• Concurrent radiotherapy allowed

Surgery:

• See Disease Characteristics

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ovarian Cancer
• Rhabdomyosarcoma
• Sarcoma
• Small Intestine Cancer

Intervention

Biological:
• dactinomycin

• filgrastim

Drug:
• carboplatin

• cyclophosphamide

• doxorubicin hydrochloride

• epirubicin hydrochloride

• etoposide

• ifosfamide

• vincristine sulfate

Procedure:
• peripheral blood stem cell transplantation

Radiation:
• radiation therapy

Locations

Country	Name	City	State
France	Centre Leon Berard	Lyon
Ireland	Our Lady's Hospital for Sick Children	Crumlin
United Kingdom	Aberdeen Royal Infirmary	Aberdeen	Scotland
United Kingdom	Royal Belfast Hospital for Sick Children	Belfast	Northern Ireland
United Kingdom	Birmingham Children's Hospital	Birmingham	England
United Kingdom	Bristol Royal Hospital for Children	Bristol	England
United Kingdom	Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust	Cambridge	England
United Kingdom	Royal Hospital for Sick Children	Edinburgh	Scotland
United Kingdom	Royal Hospital for Sick Children	Glasgow	Scotland
United Kingdom	Leicester Royal Infirmary	Leicester	England
United Kingdom	Royal Liverpool Children's Hospital, Alder Hey	Liverpool	England
United Kingdom	Great Ormond Street Hospital for Children NHS Trust	London	England
United Kingdom	Leeds Cancer Centre at St. James's University Hospital	London	England
United Kingdom	Meyerstein Institute of Oncology at University College of London Hospitals	London	England
United Kingdom	Saint Bartholomew's Hospital	London	England
United Kingdom	Central Manchester and Manchester Children's University Hospitals NHS Trust	Manchester	England
United Kingdom	Newcastle Upon Tyne Hospitals NHS Trust	Newcastle-Upon-Tyne	England
United Kingdom	Queen's Medical Centre	Nottingham	England
United Kingdom	Oxford Radcliffe Hospital	Oxford	England
United Kingdom	Children's Hospital - Sheffield	Sheffield	England
United Kingdom	Southampton General Hospital	Southampton	England
United Kingdom	Royal Marsden NHS Foundation Trust - Surrey	Sutton	England

Sponsors (3)

Lead Sponsor	Collaborator
Societe Internationale d'Oncologie Pediatrique	Children's Cancer and Leukaemia Group, Societe Francaise Oncologie Pediatrique

Countries where clinical trial is conducted

France,  Ireland,  United Kingdom, 

References & Publications (1)

McDowell HP, Foot AB, Ellershaw C, Machin D, Giraud C, Bergeron C. Outcomes in paediatric metastatic rhabdomyosarcoma: results of The International Society of Paediatric Oncology (SIOP) study MMT-98. Eur J Cancer. 2010 Jun;46(9):1588-95. doi: 10.1016/j.ej — View Citation