Clinical trial NCT00274911: Radiation Therapy Followed By Combination Chemotherapy in Treating Young Patients With Supratentorial Primitive Neuroectodermal Tumors
Official title: Hyperfractionated Accelerated Radiotherapy (HART) With Chemotherapy (Cisplatin, CCNU, Vincristine) for Non-Pineal Supratentorial Primitive Neuroectodermal Tumours
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Brain and Central Nervous System Tumors
Keywords: untreated childhood supratentorial primitive neuroectodermal tumor
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2006-01-11
Enrollment: 30
Sex: ALL
Minimum age (years): 3
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as lomustine, cisplatin, and vincristine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving radiation therapy followed by combination chemotherapy after surgery may kill any remaining tumor cells.

PURPOSE: This phase II trial is studying how well giving radiation therapy followed by combination chemotherapy works in treating young patients with supratentorial primitive neuroectodermal tumors.

Detailed description: OBJECTIVES:

Primary

* Determine the toxicity of hyperfractionated accelerated radiotherapy (HART) in pediatric patients with nonpineal supratentorial primitive neuroectodermal tumors.

Secondary

* Determine overall and relapse-free survival of patients treated with HART followed by adjuvant combination chemotherapy comprising lomustine, cisplatin, and vincristine.
* Determine the toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study.

* Radiotherapy: Patients undergo hyperfractionated accelerated radiotherapy (HART) twice a day, 5 days a week, for 5 weeks.
* Adjuvant combination chemotherapy: Six weeks after the last radiotherapy dose, patients receive oral lomustine once and cisplatin IV over 6 hours on day 1 and vincristine IV on days 1, 8, and 15 . Treatment repeats every 6 weeks for 8 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for at least 5 years.

PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically proven nonpineal supratentorial primitive neuroectodermal tumors

  * No supratentorial atypical teratoid/rhabdoid tumors or medulloepitheliomas
* Localized or metastatic disease

  * Metastatic disease is defined as unequivocal evidence of supratentorial metastases and/or spinal metastases on pre-operative or postoperative MRI scan OR tumor cells seen on cytospin analysis of lumbar cerebrospinal fluid (stage M1) performed between 15 days and 21 days after surgery
* Has undergone surgical resection within the past 4-6 weeks

PATIENT CHARACTERISTICS:

* Able to cooperate with twice daily fractions of radiotherapy
* Hemoglobin ≥ 10 g/dL
* Absolute neutrophil count ≥ 1,000/mm\^3
* Platelet count ≥ 100,000/mm\^3
* Neurologically stable (or improving) during the week before starting radiotherapy
* Lansky performance status 30-100% (for patients 1 to 16 years of age) OR
* Karnofsky performance status 30-100% (for patients over 16 years of age)
* Must be able to comply with the chemotherapy protocol (e.g., no hearing loss, renal impairment)
* No presence of active uncontrolled infection
* No previous malignant disease
* Not pregnant or nursing
* No syndrome with recognized potential for increased sensitivity to radiotherapy and/or chromosomal fragility

PRIOR CONCURRENT THERAPY:

* No previous chemotherapy or radiotherapy
* The patient should not be receiving steroids, if possible, at the start of radiotherapy or should be on a stable or reducing dose of steroids during the week before starting radiotherapy

Primary outcomes:
measure: Toxicity measured by hematological, gastrointestinal, mucosal, neurological, and skin morbidity during treatment and for 6 weeks after completion of treatment
Secondary outcomes:
measure: Overall and relapse free survival at follow up every 2 months for 1 year, every 3 months for 2 years, and then every 6 months for 2 years
Other outcomes:
Locations:
city: Dublin
country: Ireland
facility: Our Lady's Hospital for Sick Children Crumlin
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
state: England
city: Bristol
country: United Kingdom
facility: Institute of Child Health at University of Bristol
state: England
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
state: England
city: Leeds
country: United Kingdom
facility: Leeds Cancer Centre at St. James's University Hospital
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: Royal London Hospital
state: England
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children
state: England
city: Manchester
country: United Kingdom
facility: Royal Manchester Children's Hospital
state: England
city: Newcastle-Upon-Tyne
country: United Kingdom
facility: Sir James Spence Institute of Child Health at Royal Victoria Infirmary
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 - Surrey
state: England
city: Belfast
country: United Kingdom
facility: Royal Belfast Hospital for Sick Children
state: Northern Ireland
city: Aberdeen
country: United Kingdom
facility: Royal Aberdeen Children's Hospital
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
city: Cardiff
country: United Kingdom
facility: Childrens Hospital for Wales
state: Wales
Study officials:
affiliation: Royal Marsden NHS Foundation Trust
name: Frank Saran, MD
role: STUDY_CHAIR
affiliation: King's College Hospital NHS Trust
name: Christopher Chandler, MD
affiliation: Cookridge Hospital
name: Roger Taylor, MD
affiliation: Northern Centre for Cancer Treatment at Newcastle General Hospital
name: David Ellison, MD
affiliation: Royal Liverpool Children's Hospital, Alder Hey
name: Barry Pizer, MD
References: