Clinical trial NCT00025441: Combination Chemotherapy in Treating Children With Metastatic Rhabdomyosarcoma or Other Malignant Mesenchymal Tumors
Official title: MMT 98 Study For Metastatic Disease Rhabdomyosarcoma And Other Malignant Soft Tissue Sarcoma Of Childhood
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ovarian Cancer
Sarcoma
Small Intestine Cancer
Keywords: chondrosarcoma
small intestine leiomyosarcoma
fibrosarcomatous osteosarcoma
embryonal childhood rhabdomyosarcoma
alveolar childhood rhabdomyosarcoma
pleomorphic childhood rhabdomyosarcoma
mixed childhood rhabdomyosarcoma
embryonal-botryoid childhood rhabdomyosarcoma
metastatic childhood soft tissue sarcoma
extraosseous Ewing sarcoma/peripheral primitive neuroectodermal tumor
childhood fibrosarcoma
childhood synovial sarcoma
childhood malignant hemangiopericytoma
childhood liposarcoma
childhood alveolar soft-part sarcoma
childhood leiomyosarcoma
childhood angiosarcoma
childhood epithelioid sarcoma
childhood malignant mesenchymoma
stage IV uterine sarcoma
uterine leiomyosarcoma
ovarian sarcoma
previously untreated childhood rhabdomyosarcoma
childhood desmoplastic small round cell tumor
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: Children's Cancer and Leukaemia Group
name: Societe Francaise Oncologie Pediatrique
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Lyon
country: France
facility: Centre Leon Berard
city: Crumlin
country: Ireland
facility: Our Lady's Hospital for Sick Children
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
state: England
city: Bristol
country: United Kingdom
facility: Bristol Royal Hospital for Children
state: England
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust
state: England
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
state: England
city: Liverpool
country: United Kingdom
facility: Royal Liverpool Children's Hospital, Alder Hey
state: England
city: London
country: United Kingdom
facility: Saint Bartholomew's Hospital
state: England
city: London
country: United Kingdom
facility: Leeds Cancer Centre at St. James's University Hospital
state: England
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children NHS Trust
state: England
city: London
country: United Kingdom
facility: Meyerstein Institute of Oncology at University College of London Hospitals
state: England
city: Manchester
country: United Kingdom
facility: Central Manchester and Manchester Children's University Hospitals NHS Trust
state: England
city: Newcastle-Upon-Tyne
country: United Kingdom
facility: Newcastle Upon Tyne Hospitals NHS Trust
state: England
city: Nottingham
country: United Kingdom
facility: Queen's Medical Centre
state: England
city: Oxford
country: United Kingdom
facility: Oxford Radcliffe Hospital
state: England
city: Sheffield
country: United Kingdom
facility: Children's Hospital - Sheffield
state: England
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
state: England
city: Sutton
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust - Surrey
state: England
city: Belfast
country: United Kingdom
facility: Royal Belfast Hospital for Sick Children
state: Northern Ireland
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
state: Scotland
city: Edinburgh
country: United Kingdom
facility: Royal Hospital for Sick Children
state: Scotland
city: Glasgow
country: United Kingdom
facility: Royal Hospital for Sick Children
state: Scotland
Study officials:
affiliation: Royal Liverpool Children's Hospital, Alder Hey
name: Heather P. McDowell, MD
role: STUDY_CHAIR
affiliation: Bristol Royal Hospital for Children
name: Annabel B.M. Foot
role: STUDY_CHAIR
affiliation: Centre Leon Berard
name: Christophe Bergeron
role: STUDY_CHAIR
References:
citation: 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.ejca.2010.02.051. Epub 2010 Mar 24.