Observation and/or Combination Chemotherapy After Surgery or Biopsy in Treating Young Patients With Extracranial Germ Cell Tumors

Protocol for the Treatment of Extracranial Germ Cell Tumours in Children and Adolescents (GC III)

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.

Study Overview

• Status: Unknown
• Conditions: Ovarian Cancer; Extragonadal Germ Cell Tumor; Childhood Germ Cell Tumor
• Intervention / Treatment: Drug: carboplatin; Drug: etoposide; Procedure: adjuvant therapy; Drug: cisplatin; Procedure: conventional surgery; Drug: ifosfamide; Drug: vinblastine sulfate; Biological: bleomycin sulfate

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.

• Study Type: Interventional
• Enrollment (Anticipated): 105
• Phase: Phase 3

Contacts and Locations

Study Locations

• Ireland
  • Dublin, Ireland, 12
    • Our Lady's Hospital for Sick Children Crumlin
• United Kingdom
  • England
    • Birmingham, England, United Kingdom, B4 6NH
      • Birmingham Children's Hospital
    • Bristol, England, United Kingdom, BS2 8AE
      • Institute of Child Health at University of Bristol
    • Cambridge, England, United Kingdom, CB2 2QQ
      • Addenbrooke's Hospital
    • Leeds, England, United Kingdom, LS9 7TF
      • Leeds Cancer Centre at St. James's University Hospital
    • Leicester, England, United Kingdom, LE1 5WW
      • Leicester Royal Infirmary
    • Liverpool, England, United Kingdom, L12 2AP
      • Royal Liverpool Children's Hospital, Alder Hey
    • London, England, United Kingdom, E1 1BB
      • Royal London Hospital
    • London, England, United Kingdom, WC1N 3JH
      • Great Ormond Street Hospital for Children
    • Manchester, England, United Kingdom, M27 4HA
      • Royal Manchester Children's Hospital
    • Newcastle-Upon-Tyne, England, United Kingdom, NE1 4LP
      • Sir James Spence Institute of Child Health at Royal Victoria Infirmary
    • Nottingham, England, United Kingdom, NG7 2UH
      • Queen's Medical Centre
    • Sheffield, England, United Kingdom, S10 2TH
      • Children's Hospital - Sheffield
    • Southampton, England, United Kingdom, SO16 6YD
      • Southampton General Hospital
    • Sutton, England, United Kingdom, SM2 5PT
      • Royal Marsden - Surrey
  • Northern Ireland
    • Belfast, Northern Ireland, United Kingdom, BT12 6BE
      • Royal Belfast Hospital for Sick Children
  • Scotland
    • Aberdeen, Scotland, United Kingdom, AB25 2ZG
      • Royal Aberdeen Children's Hospital
    • Edinburgh, Scotland, United Kingdom, EH9 1LF
      • Royal Hospital for Sick Children
    • Glasgow, Scotland, United Kingdom, G3 8SJ
      • Royal Hospital for Sick Children
  • Wales
    • Cardiff, Wales, United Kingdom, CF14 4XW
      • Childrens Hospital for Wales

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 17 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Event-free survival
Continuation of treatment
Development of common and follow-up strategies
Registration of all cases of mature and immature teratoma

Collaborators and Investigators

• Sponsor: Children's Cancer and Leukaemia Group
• Investigators: Principal Investigator: Juliet Hale, MD, Sir James Spence Institute of Child Health at Royal Victoria Infirmary

Study record dates

Study Major Dates

• Study Start: May 1, 2005
• Primary Completion (ANTICIPATED): May 1, 2010

Study Registration Dates

• First Submitted: January 10, 2006
• First Submitted That Met QC Criteria: January 10, 2006
• First Posted (ESTIMATE): January 11, 2006

Study Record Updates

• Last Update Posted (ESTIMATE): September 17, 2013
• Last Update Submitted That Met QC Criteria: September 16, 2013
• Last Verified: June 1, 2009

More Information

Terms related to this study

• Keywords: childhood teratoma; childhood malignant testicular germ cell tumor; childhood malignant ovarian germ cell tumor; childhood extragonadal germ cell tumor; recurrent childhood malignant germ cell tumor; childhood extracranial germ cell tumor
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Germ Cell and Embryonal; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Carboplatin; Etoposide; Cisplatin; Ifosfamide; Bleomycin; Vinblastine
• Other Study ID Numbers: CDR0000454553; CCLG-GC-2005-04; EUDRACT-2004-002503-33; EU-20584