Clinical trial NCT00274950: Observation and/or Combination Chemotherapy After Surgery or Biopsy in Treating Young Patients With Extracranial Germ Cell Tumors
Official title: Protocol for the Treatment of Extracranial Germ Cell Tumours in Children and Adolescents (GC III)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Childhood Germ Cell Tumor
Extragonadal Germ Cell Tumor
Ovarian Cancer
Keywords: childhood extragonadal germ cell tumor
childhood malignant ovarian germ cell tumor
childhood malignant testicular germ cell tumor
recurrent childhood malignant germ cell tumor
childhood teratoma
childhood extracranial germ cell tumor
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2006-01-11
Enrollment: 105
Sex: ALL
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Sometimes, after surgery, the tumor may not need additional treatment until it progresses. In this case, observation may be sufficient. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Giving combination chemotherapy after surgery may kill any remaining tumor cells.

PURPOSE: This phase III trial is studying how well observation and/or combination chemotherapy works after surgery or biopsy in treating young patients with extracranial germ cell tumors.

Detailed description: OBJECTIVES:

* Stratify and reduce treatment for pediatric patients with extracranial germ cell tumors while maintaining event-free survival.
* Treat newly diagnosed patients with extracranial germ cell tumors requiring chemotherapy with a carboplatin-based strategy.
* Develop a common strategy for the treatment of patients with recurrent or progressive extracranial germ cell tumors.
* Register all cases of mature and immature teratoma.
* Develop a common strategy for the management of immature and mature teratoma, including follow-up strategies to permit early detection of yolk sac recurrence.

OUTLINE: This is a multicenter study.

Patients who have not had prior biopsy or surgical resection undergo biopsy (if feasible) or surgical resection. Patients with mature or immature teratoma undergo observation. These patients who relapse (i.e., tumor regrowth) may undergo further surgical resection unless tumor markers are significantly elevated. If the tumor markers are significantly elevated, these patients proceed to JEB chemotherapy according to risk group. Patients with all other malignant germ cell tumors are assigned to 1 of 3 treatment groups according to risk.

* Low-risk group: Patients with normal tumor markers undergo observation. Patients with rising tumor markers only AND no imageable tumor proceed to treatment as in the intermediate-risk group. Patients with rising tumor markers AND/OR imageable tumor are considered to have relapsed and proceed to treatment as in the intermediate- or high-risk group.
* Intermediate-risk group: Patients receive JEB chemotherapy comprising etoposide IV over 4 hours on days 1-3, carboplatin IV over 1 hour on day 2, and bleomycin IV over 30 minutes on day 3. Treatment repeats every 21 days for 4 courses. Patients with residual tumors after completion of chemotherapy may undergo second-look surgery.
* High-risk group: Patients receive JEB chemotherapy as in the intermediate-risk group for 6 courses. Patients with residual tumors after completion of chemotherapy may undergo second-look surgery.
* Relapse therapy: Patients in the intermediate- or high-risk group who relapse after completion of JEB chemotherapy receive vinblastine IV on days 1 and 2, ifosfamide IV over 1 hour on days 1-5, and cisplatin IV on days 1-5. Treatment repeats every 21 days for 6 courses.

PROJECTED ACCRUAL: A total of 105 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically\* proven extracranial malignant germ cell tumor (GCT), including mature/immature teratoma, with or without elevated alpha-fetoprotein (AFP) or human chorionic gonadotropin (HCG) levels

  * Newly diagnosed disease
  * Patients with relapsed or progressive extracranial malignant GCT allowed if previously treated with carboplatin, etoposide, and bleomycin (JEB) chemotherapy

    * Patients relapsing following JEB are eligible for the study relapse strategy NOTE: \*Patients with unequivocally raised AFP/HCG whose risk of biopsy is felt to be high can be diagnosed by clinical grounds, imaging, and markers
* No intracranial GCTs

PATIENT CHARACTERISTICS:

* Neutrophil count ≥ 1,000/mm\^3
* Platelet count ≥ 100,000/mm\^3
* Bilirubin ≤ 2 times upper limit of normal (ULN)
* ALT ≤ 3 times ULN
* Not pregnant or nursing

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* No prior chemotherapy other than JEB

Primary outcomes:
measure: Event-free survival
measure: Continuation of treatment
measure: Development of common and follow-up strategies
measure: Registration of all cases of mature and immature teratoma
Secondary outcomes:
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: 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: Sir James Spence Institute of Child Health at Royal Victoria Infirmary
name: Juliet Hale, MD
role: PRINCIPAL_INVESTIGATOR
References: