Brain TumorsPhase 2NCT00031590
Low-Dose Radiation and Combination Chemotherapy Following Surgery in Children With Newly Diagnosed Medulloblastoma
A Phase 2 study testing Cisplatin, Cyclophosphamide and Etoposide in people with Brain Tumors and Central Nervous System Tumors, run by Children's Hospital of Philadelphia at 3 sites in United States.
Trial summary
RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells, but also damages normal cells in the developing brains of children. Combining low-dose radiation therapy in combination with chemotherapy should be effective in treating medulloblastoma while avoiding the long-term side effects of giving… Read more about this study
- Who is it for?
- Ages 3 to 30 years
- Conditions the study is for
- Brain Tumors, Central Nervous System Tumors, Medulloblastoma
- What is being tested?
- Cisplatin, Cyclophosphamide and Etoposide
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 3 sitesUnited States
- Study dates
- Apr 2001to May 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 3 to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Histologically confirmed medulloblastoma
- Standard-risk disease
- No residual tumor greater than 1.5 cm^2 after resection by postoperative MRI
- No tumor in the spinal or cerebral subarachnoid space by MRI
- No tumor in the subarachnoid space by Cerebrospinal fluid (CSF)
- No failure to perform staging studies (spine MRI and CSF cytology) preoperatively or postoperatively
- Must begin radiotherapy on study within 28 days after surgery
Who cannot join
- Prior radiotherapy and anti-tumor chemotherapy other than corticosteroids are not allowed.
- Pregnant females will not be eligible
- Patients must begin radiotherapy on protocol within 28 days of completion of surgery. Exceptions need to be approved by the Principal Investigator.
- Patients with the following will not be eligible:
- > 1.5cm3 residual tumor following resection as indicated by post-operative MRI.
- tumor in spinal or cerebral subarachnoid space either by MRI of brain and spine
- tumor in subarachnoid space by CSF cytology
- failure to perform staging studies (spine MRI, CSF cytology) either pre- or post- operatively
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Winship Cancer Institute of Emory University
Atlanta, Georgia, 30322
Lucile Packard Children's Hospital at Stanford University Medical Center
Palo Alto, California, 94304
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104-4318
About this study
Official title: Study Of Reduced Dose Craniospinal Radiotherapy (1800 cGy) And Chemotherapy In Children With Newly-Diagnosed Standard-Risk Posterior Fossa Primitive Neuro-ectodermal Tumor (PNET/Medulloblastoma)
RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells, but also damages normal cells in the developing brains of children. Combining low-dose radiation therapy in combination with chemotherapy should be effective in treating medulloblastoma while avoiding the long-term side effects of giving higher dose radiation to children with newly diagnosed average risk medulloblastoma.
Read the detailed description
OBJECTIVES:
- By giving reduced dose craniospinal radiation followed by nine cycles of maintenance chemotherapy comprised of alternating cycles of lomustine, cisplatin, and vincristine alternating with cyclophosphamide and etoposide, we will reduce the late effects of higher dose radiation in children while maintaining the therapeutic efficacy (86% 3-year relapse-free survival) of current standard therapy
- To evaluate the late neurotoxic effects of low-dose craniospinal radiotherapy, in terms of cognitive, endocrinologic, and auditory function, in these patients.
OUTLINE: This is a multi center study of reduced dose craniospinal radiotherapy and chemotherapy in patients ages 3 - 30 years with newly diagnosed average risk medulloblastoma.
- Induction chemoradiotherapy: Beginning within 28 days after complete surgical resection, patients undergo radiotherapy to the craniospinal axis (1800 centigray (cGy)) followed by conformal radiotherapy to the tumor bed (5400 cGy). Patients receive vincristine weekly for 6 weeks.
- Maintenance chemotherapy: Beginning 4 weeks after the completion of craniospinal radiation therapy, patients receive two 6-week courses of regimen A as outlined below alternating with one 6-week course of regimen B for a total of 9 courses (AABAABAAB).
- Regimen A: Patients receive oral lomustine and cisplatin on day 0 and vincristine on days 0, 7, and 14.
- Regimen B: Patients receive cyclophosphamide on days 0 and 1 and etoposide intravenous (IV) on days 0 and 1, followed by oral etoposide on days 14-34.
Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter with surveillance neuroimaging using Magnetic Resonance Imaging Scan (MRI scan) and clinical examination.
PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study within 3 years.
- Conditions
- Brain Tumors, Central Nervous System Tumors, Medulloblastoma
- Being tested
- Cisplatin, Cyclophosphamide, Etoposide, Lomustine, Vincristine
- Keywords
- average risk medulloblastoma, craniospinal radiotherapy, newly diagnosed
- Medical subject headings
- Brain Neoplasms, Central Nervous System Neoplasms, Medulloblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CisplatinDrug
Also called CDDP, Platinum
Given at a dose of 70mg/m2 by intravenous (IV) infusion over 8 hours on day 0 of each cycle (Regimen A only).
CyclophosphamideDrug
Also called Cytoxan
Given at a dose of 1g/m2/day by IV infusion on days 0 and 1 of a 6-week cycle. Administration of cyclophosphamide will always be preceded by prehydration and Mesna (Regimen B only).
EtoposideDrug
Also called VP-16
Given at a dose of 150mg/m2/day by IV infusion on days 0 and 1 of a 6-week cycle. Given orally at a dose of 50mg/m2 as a single daily dose for 21 days beginning on day 14 of a cycle (Regimen B only).
LomustineDrug
Also called CCNU
Given at a dose of 75mg/m2 taken orally on days 0 of each 6-week cycle with vincristine and cisplatin (Regimen A only).
VincristineDrug
Also called Oncovin
Given at a dose of 1.5mg/m2 given by IV infusion once a week for the first six weeks of treatment during radiation therapy. During maintenance therapy, it will be given as an IV push on days 0, 7 and 14 of each 6-week cycle (Regimen A only).
Craniospinal RadiationRadiation
Also called Radiation
Craniospinal radiation will begin within 28 days of surgery. Craniospinal Radiation therapy will last for 6 weeks, five days per week. Once a week during radiation, subjects will also be treated with chemotherapy (vincristine).
| Study group | Role | What they receive |
|---|---|---|
| Study Treatment | Experimental | All subjects will undergo routine surgical staging of their tumor. Treatment must begin within 28 days of surgery. Craniospinal Radiation therapy will last for 6 weeks, five days per week. Once a week during radiation, subjects will also be treated with vincristine. 4 weeks after radiation and vincristine treatment is completed, all subjects will begin 9 cycles (each cycle lasts 6 weeks) of "maintenance chemotherapy" which will be given as 2 different drug combinations, Regimen A (Lomustine, Vincristine, and Cisplatin) and Regimen B (Cyclophosphamide, given with Mesna, and Etoposide [IV and oral]) which will be given in the following order: AABAABAAB (total of 54 weeks). Receives: Drug: Cisplatin; Drug: Cyclophosphamide; Drug: Etoposide; Drug: Lomustine; Drug: Vincristine; Radiation: Craniospinal Radiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate Rate of Late Neurotoxic Effects
Evaluate the late neurotoxic effects of low dose craniospinal radiation, including neurocognitive decline as measured by serial neurocognitive testing.
Measured: 3 years
Secondary outcomes (1)
Long Term Survival
Survival Endpoints:
Event free survival and overall survival were assessed at 5 years from time of study enrollment
Measured: Up to 5 years from date of randomization until the date of first documented progression or date of death from any cause, whichever came first.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startApr 2001
- Primary completionMay 2011
- Study completionMay 2011
Why it stopped: The study was terminated prematurely due to slow accrual.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Brain TumorsStudies of the same condition, open and under way.
- More trials run by Children's Hospital of PhiladelphiaThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Philadelphia
- Sponsor type
- University, hospital or other
- Collaborators
- Stanford University, Emory University
- Responsible party
- Sponsor
- Investigators
- Peter C. Phillips, MD, Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00031590
- Sponsor's protocol ID
- 00-002301
- Other IDs
- CHP-693
- Status last verified
- Apr 2019
- First submitted
- 8 Mar 2002
- Last updated
- 25 Apr 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Minturn JE, Mochizuki AY, Partap S, Belasco JB, Lange BJ, Li Y, Phillips PC, Gibbs IC, Fisher PG, Fisher MJ, Janss AJ. A Pilot Study of Low-Dose Craniospinal Irradiation in Patients With Newly Diagnosed Average-Risk Medulloblastoma. Front Oncol. 2021 Sep 2;11:744739. doi: 10.3389/fonc.2021.744739. eCollection 2021.
PubMed 34540703
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study Of Reduced Dose Craniospinal Radiotherapy (1800 cGy) And Chemotherapy In Children With Newly-Diagnosed Standard-Risk Posterior Fossa Primitive Neuro-ectodermal Tumor (PNET/Medulloblastoma)
- ClinicalTrials.gov ID
- NCT00031590
- Acronym / sponsor ID
- 00-002301
- Conditions
- Brain Tumors, Central Nervous System Tumors, Medulloblastoma
- Keywords
- average risk medulloblastoma, craniospinal radiotherapy, newly diagnosed
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated prematurely due to slow accrual.
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Children's Hospital of PhiladelphiaUniversity, hospital or other
- Collaborators
- Stanford University, Emory University
- Study start
- Apr 2001
- Primary completion
- May 2011 (actual)
- Study completion
- May 2011 (actual)
- First posted
- 27 Jan 2003 (estimated)
- Results
- Posted 25 Apr 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells, but also damages normal cells in the developing brains of children. Combining low-dose radiation therapy in combination with chemotherapy should be effective in treating medulloblastoma while avoiding the long-term side effects of giving higher dose radiation to children with newly diagnosed average risk medulloblastoma.
Detailed description
OBJECTIVES:
- By giving reduced dose craniospinal radiation followed by nine cycles of maintenance chemotherapy comprised of alternating cycles of lomustine, cisplatin, and vincristine alternating with cyclophosphamide and etoposide, we will reduce the late effects of higher dose radiation in children while maintaining the therapeutic efficacy (86% 3-year relapse-free survival) of current standard therapy
- To evaluate the late neurotoxic effects of low-dose craniospinal radiotherapy, in terms of cognitive, endocrinologic, and auditory function, in these patients.
OUTLINE: This is a multi center study of reduced dose craniospinal radiotherapy and chemotherapy in patients ages 3 - 30 years with newly diagnosed average risk medulloblastoma.
- Induction chemoradiotherapy: Beginning within 28 days after complete surgical resection, patients undergo radiotherapy to the craniospinal axis (1800 centigray (cGy)) followed by conformal radiotherapy to the tumor bed (5400 cGy). Patients receive vincristine weekly for 6 weeks.
- Maintenance chemotherapy: Beginning 4 weeks after the completion of craniospinal radiation therapy, patients receive two 6-week courses of regimen A as outlined below alternating with one 6-week course of regimen B for a total of 9 courses (AABAABAAB).
- Regimen A: Patients receive oral lomustine and cisplatin on day 0 and vincristine on days 0, 7, and 14.
- Regimen B: Patients receive cyclophosphamide on days 0 and 1 and etoposide intravenous (IV) on days 0 and 1, followed by oral etoposide on days 14-34.
Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter with surveillance neuroimaging using Magnetic Resonance Imaging Scan (MRI scan) and clinical examination.
PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study within 3 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Study Treatment | Experimental | Drug: Cisplatin, Drug: Cyclophosphamide, Drug: Etoposide, Drug: Lomustine, Drug: Vincristine, Radiation: Craniospinal RadiationAll subjects will undergo routine surgical staging of their tumor. Treatment must begin within 28 days of surgery. Craniospinal Radiation therapy will last for 6 weeks, five days per week. Once a week during radiation, subjects will also be treated with vincristine. 4 weeks after radiation and vincristine treatment is completed, all subjects will begin 9 cycles (each cycle lasts 6 weeks) of "maintenance chemotherapy" which will be given as 2 different drug combinations, Regimen A (Lomustine, Vincristine, and Cisplatin) and Regimen B (Cyclophosphamide, given with Mesna, and Etoposide [IV and oral]) which will be given in the following order: AABAABAAB (total of 54 weeks). |
Who may qualify
- Ages
- 3 to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- Histologically confirmed medulloblastoma
- Standard-risk disease
- No residual tumor greater than 1.5 cm^2 after resection by postoperative MRI
- Must begin radiotherapy on study within 28 days after surgery
Key exclusion criteria (8 listed)
- Prior radiotherapy and anti-tumor chemotherapy other than corticosteroids are not allowed.
- Pregnant females will not be eligible
- Patients must begin radiotherapy on protocol within 28 days of completion of surgery. Exceptions need to be approved by the Principal Investigator.
- Patients with the following will not be eligible:
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 |
|---|---|---|
| CisplatinAlso: CDDP, PlatinumGiven at a dose of 70mg/m2 by intravenous (IV) infusion over 8 hours on day 0 of each cycle (Regimen A only). | Drug | Study Treatment |
| CyclophosphamideAlso: CytoxanGiven at a dose of 1g/m2/day by IV infusion on days 0 and 1 of a 6-week cycle. Administration of cyclophosphamide will always be preceded by prehydration and Mesna (Regimen B only). | Drug | Study Treatment |
| EtoposideAlso: VP-16Given at a dose of 150mg/m2/day by IV infusion on days 0 and 1 of a 6-week cycle. Given orally at a dose of 50mg/m2 as a single daily dose for 21 days beginning on day 14 of a cycle (Regimen B only). | Drug | Study Treatment |
| LomustineAlso: CCNUGiven at a dose of 75mg/m2 taken orally on days 0 of each 6-week cycle with vincristine and cisplatin (Regimen A only). | Drug | Study Treatment |
| VincristineAlso: OncovinGiven at a dose of 1.5mg/m2 given by IV infusion once a week for the first six weeks of treatment during radiation therapy. During maintenance therapy, it will be given as an IV push on days 0, 7 and 14 of each 6-week cycle (Regimen A only). | Drug | Study Treatment |
| Craniospinal RadiationAlso: RadiationCraniospinal radiation will begin within 28 days of surgery. Craniospinal Radiation therapy will last for 6 weeks, five days per week. Once a week during radiation, subjects will also be treated with chemotherapy (vincristine). | Radiation | Study Treatment |
Primary outcome
Evaluate Rate of Late Neurotoxic Effects
Time frame: 3 years
Evaluate the late neurotoxic effects of low dose craniospinal radiation, including neurocognitive decline as measured by serial neurocognitive testing.
1 secondary outcome
Long Term Survival
Time frame: Up to 5 years from date of randomization until the date of first documented progression or date of death from any cause, whichever came first.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34540703Minturn JE, Mochizuki AY, Partap S, Belasco JB, Lange BJ, Li Y, Phillips PC, Gibbs IC, Fisher PG, Fisher MJ, Janss AJ. A Pilot Study of Low-Dose Craniospinal Irradiation in Patients With Newly Diagnosed Average-Risk Medulloblastoma. Front Oncol. 2021 Sep 2;11:744739. doi: 10.3389/fonc.2021.744739. eCollection 2021.
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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.
Peter C. Phillips, MD principal investigator
Children's Hospital of Philadelphia
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cisplatin, Cyclophosphamide and Etoposide in people with Brain Tumors and Central Nervous System Tumors, run by Children's Hospital of Philadelphia at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 25 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Evaluate Rate of Late Neurotoxic Effects (time frame: 3 years). 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 NCT00031590, 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 25 Apr 2019.