Brain and Central Nervous System TumorsPhase 3NCT00293358
Combination Chemotherapy and Radiation Therapy in Treating Patients With Germ Cell Tumors in the Brain
A Phase 3 study testing carboplatin, cisplatin and etoposide phosphate in people with Brain and Central Nervous System Tumors, run by Children's Cancer and Leukaemia Group at 21 sites in 2 countries.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as carboplatin, etoposide, ifosfamide, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Brain and Central Nervous System Tumors
- What is being tested?
- carboplatin, cisplatin and etoposide phosphate
- Type of treatment
- Surgery or procedure
- How many people
- 500 participants
- Where
- 21 sitesin 2 countries
- Study dates
- Jan 1997to Dec 2006
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
DISEASE CHARACTERISTICS:
- Clinical and radiological evidence of intracranial germ cell tumor, classified as 1 of the following:
- Germinoma
- Pure germinoma
- Germinoma with mature and/or immature teratoma
- Secreting germ cell tumor
- Elevated tumor markers in serum and/or cerebral spinal fluid as evidenced by any of the following:
- Alpha-fetoprotein > 25 ng/mL
- β-human choriogonadotropin > 50 IU/L
- Any tumor containing 1 of these components:
- Yolk sac tumor
- Choriocarcinoma
- Embryonal tumor
- Normal tumor markers allowed
- Diagnosis confirmed by histology or elevated serum markers
- Metastatic or nonmetastatic disease
- Two separate tumors in the suprasellar and pineal areas without evidence of metastatic disease elsewhere are considered nonmetastatic multifocal disease
- Study treatment must begin ≤ 4 weeks after diagnosis
- No pure immature or mature teratomas
- The following additional patients are eligible:
- Patients who are > 18 years of age provided no other appropriate protocol exists
- Patients who were diagnosed > 4 weeks ago
- Patients who are in relapse
PATIENT CHARACTERISTICS:
- Not specified
PRIOR CONCURRENT THERAPY:
- No prior treatment except surgery
- No concurrent amino glycosides or other nephrotoxic drugs during ifosfamide administration
- No concurrent growth factors
- No other concurrent chemotherapy or radiotherapy
Trial locations and contacts
21 sites in 2 countries.
21 sites in 2 countries
United Kingdom20 sites
Royal Aberdeen Children's Hospital
Aberdeen, Scotland, AB25 2ZG
Royal Belfast Hospital for Sick Children
Belfast, Northern Ireland, BT12 6BE
Birmingham Children's Hospital
Birmingham, England, B4 6NH
Institute of Child Health at University of Bristol
Bristol, England, BS2 8AE
Addenbrooke's Hospital at Cambridge University Hospitals NHS Foundation Trust
Cambridge, England, CB2 2QQ
Childrens Hospital for Wales
Cardiff, Wales, CF14 4XW
Royal Hospital for Sick Children
Edinburgh, Scotland, EH9 1LF
Royal Hospital for Sick Children
Glasgow, Scotland, G3 8SJ
Leeds Cancer Centre at St. James's University Hospital
Leeds, England, LS9 7TF
Leicester Royal Infirmary
Leicester, England, LE1 5WW
Royal Liverpool Children's Hospital, Alder Hey
Liverpool, England, L12 2AP
Royal London Hospital
London, England, E1 1BB
Great Ormond Street Hospital for Children NHS Trust
London, England, WC1N 3JH
Central Manchester and Manchester Children's University Hospitals NHS Trust
Manchester, England, M27 4HA
Sir James Spence Institute of Child Health
Newcastle upon Tyne, England, NE1 4LP
Queen's Medical Centre
Nottingham, England, NG7 2UH
Oxford Radcliffe Hospital
Oxford, England, 0X3 9DU
Children's Hospital - Sheffield
Sheffield, England, S10 2TH
Southampton General Hospital
Southampton, England, SO16 6YD
Royal Marsden NHS Foundation Trust - Surrey
Sutton, England, SM2 5PT
About this study
Official title: SIOP Intracranial Germ Cell Tumours Protocol
RATIONALE: Drugs used in chemotherapy, such as carboplatin, etoposide, ifosfamide, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving more than one drug (combination chemotherapy) with radiation therapy may kill more tumor cells.
PURPOSE: This phase III trial is studying combination chemotherapy followed by radiation therapy to see how well it works compared to radiation therapy alone in treating patients with germ cell tumors in the brain.
Read the detailed description
OBJECTIVES:
Primary
- Evaluate and compare, in a non-randomized protocol, reduced-dose craniospinal radiotherapy alone or combination chemotherapy comprising carboplatin, etoposide phosphate, and ifosfamide and local irradiation in patients with intracranial germinoma.
- Increase survival with combination chemotherapy comprising cisplatin, etoposide phosphate, and ifosfamide followed by focal radiotherapy or craniospinal irradiation in patients with intracranial secreting germ cell tumors.
Secondary
- Use the same diagnostic protocol for imaging and laboratory investigations before, during, and after treatment.
- Establish and use a common documentation system regarding general patient's data, including diagnostic tests, clinical evaluation, surgery, histology, radiotherapy, chemotherapy, and toxicity.
- Collect information about toxicity, prognostic factors, and tumor markers.
- Collect epidemiological data, including documentation of incidence and the site and the histologic pattern of intracranial secreting and nonsecreting germ cell tumors in children and adolescents.
- Register associated malformations in the patients as well as the epidemiology of tumors and malformations in relatives.
OUTLINE: This is a non-randomized, multicenter study. Patients are stratified according to tumor classification (pure CNS germinoma vs secreting germ cell tumor and embryonal carcinoma).
Patients in stratum I undergo biopsy or surgical resection and then begin radiotherapy with or without chemotherapy.
- Stratum I (pure CNS germinoma [without elevated markers]): Patients receive 1 of 2 treatment options based on national/center standard:
- Option 1: Patients receive reduced-dose craniospinal radiotherapy 5 days a week for 3 weeks followed by a boost to the tumor bed 5 days a week for 2 weeks. Patients with multifocal or metastatic disease receive additional boosts to the tumor sites.
- Option 2: Patients receive carboplatin IV over 1 hour on day 1, etoposide phosphate IV over 1 hour on days 1-3 and 22-24, and ifosfamide IV over 3 hours on days 22-26. Treatment repeats every 6 weeks for 2 courses. After recovery from chemotherapy, patients undergo radiotherapy 5 days a week for 5 weeks.
- Stratum II (secreting tumors and embryonal carcinoma): Patients receive etoposide phosphate IV over 1 hour on days 1-3, cisplatin IV over 1 hour on days 1-5, and ifosfamide IV over 22 hours on days 1-5. Treatment repeats every 3 weeks for up to 4 courses. Patients whose tumor markers do not return to normal after completion of chemotherapy are off protocol. Patients may undergo surgery after chemotherapy course 2 or 4 if required. After completion of chemotherapy and recovery from surgery, patients with nonmetastatic disease undergo radiotherapy to the tumor bed 5 day a week for 6 weeks, and patients with metastatic disease undergo radiotherapy to the cerebrum, spinal axis, and tumor bed for 7 weeks.
After completion of study treatment, patients are followed for 4 weeks and then periodically.
PROJECTED ACCRUAL: Approximately 500 patients will be accrued for this study.
- Conditions
- Brain and Central Nervous System Tumors
- Being tested
- carboplatin, cisplatin, etoposide phosphate, ifosfamide, adjuvant therapy
- Keywords
- childhood central nervous system germ cell tumor, adult central nervous system germ cell tumor, childhood central nervous system choriocarcinoma, childhood central nervous system embryonal tumor, childhood central nervous system yolk sac tumor
- Medical subject headings
- Central Nervous System Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
carboplatinDrug
cisplatinDrug
etoposide phosphateDrug
ifosfamideDrug
adjuvant therapyProcedure or surgery
conventional surgeryProcedure or surgery
neoadjuvant therapyProcedure or surgery
radiation therapyRadiation
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival
Event-free survival
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2006 (estimated)
- Study startJan 1997
- Study completionDec 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Brain and Central Nervous System TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Enrolment
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Cancer and Leukaemia Group
- Sponsor type
- University, hospital or other
- Investigators
- James Nicholson, DM, MA, MRCPCH, Study chair, Cambridge University Hospitals NHS Foundation TrustMarie C. Baranzelli, MD, Centre Oscar LambretU. Gobel, MD, Heinrich-Heine University, Duesseldorf
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00293358
- Sponsor's protocol ID
- CDR0000455625
- Other IDs
- CCLG-GC-1997-01, EU-20579, SIOP-CNS-GCT-96
- Status last verified
- Jul 2008
- First submitted
- 16 Feb 2006
- Last updated
- 17 Sep 2013
- Results posted
- No
Publications
Rajagopal R, Leong SH, Jawin V, Foo JC, Ahmad Bahuri NF, Mun KS, Azman RR, Loh J, Yap TY, Ariffin H, Moreira DC, Gottardo NG, Bouffet E, Ganesan D. Challenges in the Management of Childhood Intracranial Germ Cell Tumors in Middle-Income Countries: A 20-Year Retrospective Review From a Single Tertiary Center in Malaysia. J Pediatr Hematol Oncol. 2021 Oct 1;43(7):e913-e923. doi: 10.1097/MPH.0000000000002116.
PubMed 33633029
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- SIOP Intracranial Germ Cell Tumours Protocol
- ClinicalTrials.gov ID
- NCT00293358
- Acronym / sponsor ID
- CDR0000455625
- Conditions
- Brain and Central Nervous System Tumors
- Keywords
- childhood central nervous system germ cell tumor, adult central nervous system germ cell tumor, childhood central nervous system choriocarcinoma, childhood central nervous system embryonal tumor, childhood central nervous system yolk sac tumor
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 500 participants (estimated)
- Lead sponsor
- Children's Cancer and Leukaemia GroupUniversity, hospital or other
- Study start
- Jan 1997
- Study completion
- Dec 2006 (actual)
- First posted
- 17 Feb 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Drugs used in chemotherapy, such as carboplatin, etoposide, ifosfamide, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving more than one drug (combination chemotherapy) with radiation therapy may kill more tumor cells.
PURPOSE: This phase III trial is studying combination chemotherapy followed by radiation therapy to see how well it works compared to radiation therapy alone in treating patients with germ cell tumors in the brain.
Detailed description
OBJECTIVES:
Primary
- Evaluate and compare, in a non-randomized protocol, reduced-dose craniospinal radiotherapy alone or combination chemotherapy comprising carboplatin, etoposide phosphate, and ifosfamide and local irradiation in patients with intracranial germinoma.
- Increase survival with combination chemotherapy comprising cisplatin, etoposide phosphate, and ifosfamide followed by focal radiotherapy or craniospinal irradiation in patients with intracranial secreting germ cell tumors.
Secondary
- Use the same diagnostic protocol for imaging and laboratory investigations before, during, and after treatment.
- Establish and use a common documentation system regarding general patient's data, including diagnostic tests, clinical evaluation, surgery, histology, radiotherapy, chemotherapy, and toxicity.
- Collect information about toxicity, prognostic factors, and tumor markers.
- Collect epidemiological data, including documentation of incidence and the site and the histologic pattern of intracranial secreting and nonsecreting germ cell tumors in children and adolescents.
- Register associated malformations in the patients as well as the epidemiology of tumors and malformations in relatives.
OUTLINE: This is a non-randomized, multicenter study. Patients are stratified according to tumor classification (pure CNS germinoma vs secreting germ cell tumor and embryonal carcinoma).
Patients in stratum I undergo biopsy or surgical resection and then begin radiotherapy with or without chemotherapy.
- Stratum I (pure CNS germinoma [without elevated markers]): Patients receive 1 of 2 treatment options based on national/center standard:
- Option 1: Patients receive reduced-dose craniospinal radiotherapy 5 days a week for 3 weeks followed by a boost to the tumor bed 5 days a week for 2 weeks. Patients with multifocal or metastatic disease receive additional boosts to the tumor sites.
- Option 2: Patients receive carboplatin IV over 1 hour on day 1, etoposide phosphate IV over 1 hour on days 1-3 and 22-24, and ifosfamide IV over 3 hours on days 22-26. Treatment repeats every 6 weeks for 2 courses. After recovery from chemotherapy, patients undergo radiotherapy 5 days a week for 5 weeks.
- Stratum II (secreting tumors and embryonal carcinoma): Patients receive etoposide phosphate IV over 1 hour on days 1-3, cisplatin IV over 1 hour on days 1-5, and ifosfamide IV over 22 hours on days 1-5. Treatment repeats every 3 weeks for up to 4 courses. Patients whose tumor markers do not return to normal after completion of chemotherapy are off protocol. Patients may undergo surgery after chemotherapy course 2 or 4 if required. After completion of chemotherapy and recovery from surgery, patients with nonmetastatic disease undergo radiotherapy to the tumor bed 5 day a week for 6 weeks, and patients with metastatic disease undergo radiotherapy to the cerebrum, spinal axis, and tumor bed for 7 weeks.
After completion of study treatment, patients are followed for 4 weeks and then periodically.
PROJECTED ACCRUAL: Approximately 500 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| carboplatin | Drug | – |
| cisplatin | Drug | – |
| etoposide phosphate | Drug | – |
| ifosfamide | Drug | – |
| adjuvant therapy | Procedure or surgery | – |
| conventional surgery | Procedure or surgery | – |
| neoadjuvant therapy | Procedure or surgery | – |
| radiation therapy | Radiation | – |
Primary outcome
Survival
Event-free survival
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2013.
- Derived from this study: PubMed 33633029Rajagopal R, Leong SH, Jawin V, Foo JC, Ahmad Bahuri NF, Mun KS, Azman RR, Loh J, Yap TY, Ariffin H, Moreira DC, Gottardo NG, Bouffet E, Ganesan D. Challenges in the Management of Childhood Intracranial Germ Cell Tumors in Middle-Income Countries: A 20-Year Retrospective Review From a Single Tertiary Center in Malaysia. J Pediatr Hematol Oncol. 2021 Oct 1;43(7):e913-e923. doi: 10.1097/MPH.0000000000002116.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James Nicholson, DM, MA, MRCPCH study chair
Cambridge University Hospitals NHS Foundation Trust
Marie C. Baranzelli, MD
Centre Oscar Lambret
U. Gobel, MD
Heinrich-Heine University, Duesseldorf
21 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing carboplatin, cisplatin and etoposide phosphate in people with Brain and Central Nervous System Tumors, run by Children's Cancer and Leukaemia Group at 21 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Sep 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in United Kingdom, Ireland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Survival. The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00293358, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2013.