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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00392886




Registration number
NCT00392886
Ethics application status
Date submitted
25/10/2006
Date registered
26/10/2006
Date last updated
18/12/2013

Titles & IDs
Public title
Combination Chemotherapy With or Without Etoposide Followed By an Autologous Stem Cell Transplant in Treating Young Patients With Previously Untreated Malignant Brain Tumors
Scientific title
Dose Intensive Chemotherapy for Children Less Than Ten Years of Age Newly-Diagnosed With Malignant Brain Tumors: A Pilot Study of Two Alternative Intensive Induction Chemotherapy Regimens, Followed by Consolidation With Myeloablative Chemotherapy (Thiotepa and Carboplatin, With or Without Etoposide) and Autologous Stem Cell Rescue [HEAD START III]
Secondary ID [1] 0 0
CHLA-HEAD-START-III
Secondary ID [2] 0 0
CDR0000503990
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Brain and Central Nervous System Tumors 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain
Cancer 0 0 0 0
Neuroendocrine tumour (NET)
Cancer 0 0 0 0
Children's - Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - carboplatin
Treatment: Drugs - cisplatin
Treatment: Drugs - cyclophosphamide
Treatment: Drugs - etoposide
Treatment: Drugs - methotrexate
Treatment: Drugs - temozolomide
Treatment: Drugs - thiotepa
Treatment: Drugs - vincristine sulfate
Treatment: Surgery - autologous bone marrow transplantation
Treatment: Surgery - autologous hematopoietic stem cell transplantation
Treatment: Surgery - peripheral blood stem cell transplantation
Treatment: Other - radiation therapy

Experimental: Regimen C - Patients receive induction therapy of vincristine IV on days 1, 8, and 15 of courses 1-3, oral temozolomide once daily on days 1-5, and carboplatin IV over 4 hours on days 1 and 2. Patients also receive G-CSF SC beginning on day 6 and continuing until blood counts recover. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients receive consolidation therapy of carboplatin IV over 4 hours on days -8 to -6 and thiotepa IV over 3 hours on days -5 to -3, undergo reinfusion of bone marrow or peripheral blood stem cells on day 0, and receive G-CSF SC beginning on day 1 and continuing until blood counts recover. Beginning within 6 weeks after transplantation, some patients undergo radiotherapy once daily 5 days a week for 4-6 weeks in the absence of disease progression or unacceptable toxicity and some patients undergo radiotherapy if there is evidence of tumor remaining after completion of induction chemotherapy.

Experimental: Regimen D2 - In courses 1, 3, and 5, patients receive cisplatin IV over 6 hours on day 1, cyclophosphamide IV over 1 hour and etoposide IV over 2 hours on days 2 and 3, high-dose methotrexate IV over 4 hours on day 4, vincristine IV on days 1, 8, and 15 (in courses1 and 3), and filgrastim (G-CSF) subcutaneously (SC) beginning on day 5 and continuing until blood counts recover. In courses 2 and 4, patients receive oral temozolomide once daily on days 1-5, oral etoposide once daily on days 1-10, cyclophosphamide IV over 1 hour on days 11 and 12, vincristine IV on days 1, 8, and 15 (in course 2), and G-CSF SC beginning on day 13 and continuing until blood counts recover. Patients receive consolidation therapy as in regimen C in combination with etoposide IV over 3 hours on days -5 to -3 and undergo autologous bone marrow or peripheral blood stem cell transplantation, receive G-CSF, and undergo radiotherapy as in regimen C.


Treatment: Drugs: carboplatin
Given IV

Treatment: Drugs: cisplatin
Given IV

Treatment: Drugs: cyclophosphamide
Given IV

Treatment: Drugs: etoposide
Given IV and orally

Treatment: Drugs: methotrexate
Given IV

Treatment: Drugs: temozolomide
Given orally

Treatment: Drugs: thiotepa
Given IV

Treatment: Drugs: vincristine sulfate
Given IV

Treatment: Surgery: autologous bone marrow transplantation
Given on day 0

Treatment: Surgery: autologous hematopoietic stem cell transplantation
Given on day 0

Treatment: Surgery: peripheral blood stem cell transplantation
Given on day 0

Treatment: Other: radiation therapy
Some patients undergo radiation therapy once daily, 5 days a week for 4-6 weeks.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Surgery
Intervention code [3] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time to tumor progression, disease recurrence, or death of any cause
Timepoint [1] 0 0
Primary outcome [2] 0 0
Event-free survival at 2 years
Timepoint [2] 0 0
Primary outcome [3] 0 0
Toxicity
Timepoint [3] 0 0
Secondary outcome [1] 0 0
Response to induction as assessed by one-time tumor measurements at baseline and after completion of induction chemotherapy
Timepoint [1] 0 0
Secondary outcome [2] 0 0
Time to death
Timepoint [2] 0 0
Secondary outcome [3] 0 0
Overall survival
Timepoint [3] 0 0

Eligibility
Key inclusion criteria
DISEASE CHARACTERISTICS:

- Histologically confirmed malignant brain tumor, including any of the following:

- Posterior fossa medulloblastoma/primitive neuroectodermal tumor (PNET)*

- All stages allowed

- Must be < 4 years of age at diagnosis unless there is evidence of
postoperative residual tumor (> 1.5 cm² tumor area) or evidence of neuraxis
or extraneural dissemination (high-stage)

- Medulloblastoma, cerebral neuroblastoma, and ependymoblastoma allowed

- Low-stage (standard-risk) medulloblastoma not allowed in patients > 4
years of age

- Ependymoma*

- All stages and locations allowed

- Cellular and anaplastic subtypes allowed (no myxopapillary ependymomas of
the spinal cord)

- Must be < 36 months of age at diagnosis for posterior fossa tumor OR < 72
months of age for supratentorial tumor

- Evidence of neuraxis dissemination irrespective of primary site

- No cellular (low-grade) supratentorial ependymomas at any age with complete
resection of parenchymally based (i.e., not periventricular) supratentorial
tumors

- Brain stem tumor*

- All stages allowed irrespective of extent of resection

- No unbiopsied diffuse intrinsic pontine tumor

- Tumor pathologically confirmed to be either malignant glioma or PNET allowed

- High-grade glioma**

- Primary atypical teratoid/rhabdoid tumor of the CNS*

- Choroid plexus carcinoma or atypical choroid plexus papilloma*

- All stages and locations allowed

- Anaplastic astrocytoma**

- Glioblastoma multiforme**

- Anaplastic oligodendroglioma**

- Anaplastic ganglioglioma**

- Other anaplastic mixed gliomas**

- Small-cell glioblastoma**

- Giant-cell glioblastoma**

- Gliosarcoma**

- The following diagnoses or subtypes are not allowed:

- Choroid plexus papilloma

- Pineocytoma

- Low-grade mixed glioma

- Primary CNS germ cell tumor

- Primary CNS lymphoma

- Solid leukemic lesions (i.e., chloromas, granulocytic sarcomas)

- Pleomorphic xanthoastrocytoma, low grade

- Desmoplastic ganglioglioma

- Low-grade astrocytoma

- Previously untreated disease

- Has undergone definitive surgery within the past 42 days NOTE: *Patients receive
treatment according to regimen D2

NOTE: **Patients receive treatment according to regimen C

PATIENT CHARACTERISTICS:

- Bilirubin < 1.5 mg/dL

- ALT and AST < 2.5 times upper limit of normal

- Creatinine clearance and/or glomerular filtration rate = 60 mL/min

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- No prior radiotherapy or chemotherapy

- Prior corticosteroids allowed

- No concurrent corticosteroids for antiemesis only

- No concurrent brachytherapy or electron radiotherapy

- No concurrent dairy products or grapefruit juice with temozolomide administration
Minimum age
No limit
Maximum age
10 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Unknown status
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/03/2004
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
120
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
6001 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Delaware
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Indiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Kentucky
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
Minnesota
Country [10] 0 0
United States of America
State/province [10] 0 0
Missouri
Country [11] 0 0
United States of America
State/province [11] 0 0
New Jersey
Country [12] 0 0
United States of America
State/province [12] 0 0
New York
Country [13] 0 0
United States of America
State/province [13] 0 0
Ohio
Country [14] 0 0
United States of America
State/province [14] 0 0
Pennsylvania
Country [15] 0 0
United States of America
State/province [15] 0 0
Texas
Country [16] 0 0
Canada
State/province [16] 0 0
British Columbia
Country [17] 0 0
Canada
State/province [17] 0 0
Manitoba
Country [18] 0 0
Canada
State/province [18] 0 0
Ontario
Country [19] 0 0
New Zealand
State/province [19] 0 0
Christchurch
Country [20] 0 0
New Zealand
State/province [20] 0 0
Wellington
Country [21] 0 0
Switzerland
State/province [21] 0 0
Bern

Funding & Sponsors
Primary sponsor type
Other
Name
Children's Hospital Los Angeles
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
RATIONALE: 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. A bone marrow or
peripheral stem cell transplant using stem cells from the patient may be able to replace
blood-forming cells that were destroyed by chemotherapy. This may allow more chemotherapy to
be given so that more tumor cells are killed.

PURPOSE: This phase III trial is studying how well giving combination chemotherapy with or
without etoposide followed by an autologous stem cell transplant works in treating young
patients with previously untreated malignant brain tumors.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00392886
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jonathan L. Finlay, MB, ChB
Address 0 0
Children's Hospital Los Angeles
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00392886