Brain TumorsPhase 3NCT00002875
Radiation Therapy Plus Combination Chemotherapy in Treating Children With Medulloblastoma
A Phase 3 study testing filgrastim, cisplatin and cyclophosphamide in people with Brain Tumors and Central Nervous System Tumors, run by Children's Oncology Group at 41 sites in 5 countries.
Trial summary
RATIONALE: Radiation therapy uses high energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining radiation therapy with chemotherapy may kill more tumor cells. Read more about this study
- Who is it for?
- Ages 3 to 22 years
- Conditions the study is for
- Brain Tumors, Central Nervous System Tumors
- What is being tested?
- filgrastim, cisplatin and cyclophosphamide
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 421 participants
- Where
- 41 sitesin 5 countries
- Study dates
- Dec 1996to Jan 2011
- 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 3 to 22 years
- All sexes
- No healthy volunteers
- Child, Adult
DISEASE CHARACTERISTICS: Pathologically confirmed posterior fossa medulloblastoma (CCG diagnosis code 2041) Localized disease required, i.e.: No more than 1.5 square centimeters of residual tumor on postoperative contrast-enhanced CT or MRI (preferably within 72 hours but no more than 14 days after surgery) No evidence of metastatic disease on pre- and postoperative MRI of spine (with dye enhancement) and lumbar cerebrospinal fluid (CSF) cytology within 3 days prior to surgery Cytologic analysis of ventricular CSF allowed only if medical contraindication to lumbar puncture and with approval of study chairperson Brain stem involvement eligible
PATIENT CHARACTERISTICS: Age: 3 to 21 at diagnosis Performance status: Not specified Hematopoietic: ANC greater than 1,500/mm3 Platelet count greater than 100,000/mm3 Hemoglobin greater than 10 g/dL Hepatic: Bilirubin less than 1.5 mg/dL ALT less than 1.5 times normal Renal: Nuclear glomerular filtration rate or creatinine clearance greater than 70 mL/min per 1.73 square meters
PRIOR CONCURRENT THERAPY: No prior radiotherapy or chemotherapy (other than corticosteroids) No more than 31 days since definitive surgery
Trial locations and contacts
41 sites in 5 countries.
41 sites in 5 countries
United States36 sites
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109-0752
Lineberger Comprehensive Cancer Center, UNC
Chapel Hill, North Carolina, 27599-7295
Cancer Center, University of Virginia HSC
Charlottesville, Virginia, 22908
University of Chicago Cancer Research Center
Chicago, Illinois, 60637
Children's Hospital Medical Center - Cincinnati
Cincinnati, Ohio, 45229-3039
Ireland Cancer Center
Cleveland, Ohio, 44106-5065
Children's Hospital of Columbus
Columbus, Ohio, 43205-2696
Children's Hospital of Denver
Denver, Colorado, 80218
University of Texas - MD Anderson Cancer Center
Houston, Texas, 77030
Indiana University Cancer Center
Indianapolis, Indiana, 46202-5265
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
Children's Mercy Hospital
Kansas City, Missouri, 64108
Long Beach Memorial Medical Center
Long Beach, California, 90806
Children's Hospital Los Angeles
Los Angeles, California, 90027-0700
Jonsson Comprehensive Cancer Center, UCLA
Los Angeles, California, 90095-1781
University of Wisconsin Comprehensive Cancer Center
Madison, Wisconsin, 53792
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105-2794
University of Minnesota Cancer Center
Minneapolis, Minnesota, 55455
Vanderbilt Cancer Center
Nashville, Tennessee, 37232-6838
MBCCOP - LSU Medical Center
New Orleans, Louisiana, 70112
NYU School of Medicine's Kaplan Comprehensive Cancer Center
New York, New York, 10016
Memorial Sloan-Kettering Cancer Center
New York, New York, 10021
Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
University of Nebraska Medical Center
Omaha, Nebraska, 68198-3330
Children's Hospital of Orange County
Orange, California, 92668
St. Joseph's Hospital and Medical Center
Paterson, New Jersey, 07503
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15213
Doernbecher Children's Hospital
Portland, Oregon, 97201-3098
Mayo Clinic Cancer Center
Rochester, Minnesota, 55905
Huntsman Cancer Institute
Salt Lake City, Utah, 84132
UCSF Cancer Center and Cancer Research Institute
San Francisco, California, 94115-0128
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, 98105
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109
Children's National Medical Center
Washington D.C., District of Columbia, 20010-2970
Via Christi Regional Medical Center
Wichita, Kansas, 67214
Canada2 sites
IWK Grace Health Centre
Halifax, Nova Scotia, B3J 3G9
British Columbia Children's Hospital
Vancouver, British Columbia, V6H 3V4
Australia1 site
Princess Margaret Hospital for Children
Perth, Western Australia, 6001
Puerto Rico1 site
University of Puerto Rico School of Medicine Medical Sciences Campus
San Juan, 00936-5067
About this study
Official title: Phase III Prospective Randomized Study of Craniospinal RT Followed by One of Two Adjuvant Chemotherapy Regimens (CCNU, CDDP, VCR OR CPM, CDDP, VCR) for Newly-Diagnosed Average Risk MedulloblastomaMEDULLOBLASTOMA
RATIONALE: Radiation therapy uses high energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining radiation therapy with chemotherapy may kill more tumor cells. It is not yet known which chemotherapy regimen is more effective when combined with radiation therapy for treating medulloblastoma.
PURPOSE: Randomized phase III trial to compare two combination chemotherapy treatments plus radiation therapy in treating children with newly diagnosed medulloblastoma.
Read the detailed description
OBJECTIVES: I. Assess whether a cyclophosphamide-containing combination chemotherapy regimen increases progression-free survival compared to a lomustine-containing regimen in children with newly diagnosed, average-risk medulloblastoma. II. Determine progression-free and overall survival of children treated with craniospinal radiotherapy and local boost radiotherapy for a total dose of 5580 cGy followed by adjuvant lomustine/cisplatin/vincristine vs. cyclophosphamide/cisplatin/vincristine. III. Determine the long-term neurocognitive, endocrinologic, and cardiopulmonary sequelae associated with craniospinal radiotherapy, local boost radiotherapy, and adjuvant chemotherapy in these children, and determine whether replacement of lomustine with cyclophosphamide alters the incidence and degree of sequelae. IV. Determine whether cellular and biologic parameters, including tumor molecular genetic analysis, DNA ploidy, mitotic activity markers, and immunohistochemical analysis, are correlated with progression-free survival, overall survival, and patterns of disease relapse in these patients. V. Evaluate the utility of routine magnetic resonance imaging surveillance studies of the head and spine in detecting subclinical recurrent disease.
OUTLINE: This is a randomized study. Patients are stratified by participating institution. Following surgery, patients are randomized to one of two groups. The first group receives craniospinal irradiation followed by a boost to the primary tumor. Beginning within 1 week after initiation of radiotherapy, patients receive vincristine weekly for 8 doses. Beginning 6 weeks after the completion of radiotherapy, patients receive adjuvant lomustine/vincristine/cisplatin every 6 weeks for a total of 8 courses. The second group receives craniospinal irradiation plus vincristine as above, followed by adjuvant cyclophosphamide/vincristine/cisplatin every 6 weeks for a total of 8 courses. Patients are followed every 3 months for 1 year, every 6 months for 2 years, then annually.
PROJECTED ACCRUAL: It is anticipated that 240-300 patients will be entered over 4 years.
- Conditions
- Brain Tumors, Central Nervous System Tumors
- Being tested
- filgrastim, cisplatin, cyclophosphamide, lomustine, mesna
- Keywords
- untreated childhood medulloblastoma
- Medical subject headings
- Brain Neoplasms, Central Nervous System Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
filgrastimBiological
Also called G-CSF, Neupogen, NSC-614629
cisplatinDrug
Also called Platinol, NSC-119875
cyclophosphamideDrug
Also called Cytoxan, NSC-26271
lomustineDrug
Also called CCNU, NSC-79037
mesnaDrug
Also called Mesnex, NSC-113891
Also called Oncovin, NSC-67574
low-LET electron therapyRadiation
low-LET photon therapyRadiation
| Study group | Role | What they receive |
|---|---|---|
| Regimen A | Experimental | Following surgery, craniospinal irradiation followed by a boost to the primary tumor. Beginning within 1 week after initiation of radiotherapy, patients receive vincristine sulfate weekly for 8 doses. Beginning 6 weeks after the completion of radiotherapy, patients receive adjuvant lomustine/vincristine sulfate/cisplatin every 6 weeks for a total of 8 courses. Receives: Biological: filgrastim; Drug: cisplatin; Drug: cyclophosphamide; Drug: lomustine; Drug: mesna; Drug: vincristine sulfate; Radiation: low-LET electron therapy; Radiation: low-LET photon therapy |
| Regimen B | Experimental | Following surgery, craniospinal irradiation plus vincristine sulfate, followed by adjuvant cyclophosphamide/vincristine sulfate/cisplatin every 6 weeks for a total of 8 courses. Receives: Biological: filgrastim; Drug: cisplatin; Drug: cyclophosphamide; Drug: mesna; Drug: vincristine sulfate; Radiation: low-LET electron therapy; Radiation: low-LET photon therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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 posted24 May 2004 (estimated)
- Study startDec 1996
- Primary completionFeb 2006
- Study completionJan 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)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 Oncology GroupThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- Single blind
- Enrolment
- 421 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Oncology Group
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI), Pediatric Oncology Group
- Responsible party
- Sponsor
- Investigators
- Roger J. Packer, MD, Study chair, Children's National Research InstituteAmar Gajjar, MD, Study chair, St. Jude Children's Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00002875
- Sponsor's protocol ID
- A9961
- Other IDs
- CCG-A9961, POG-A9961, CDR0000065160
- Status last verified
- Jul 2014
- First submitted
- 1 Nov 1999
- Last updated
- 1 Aug 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Turgut M. Cerebellar mutism. J Neurosurg Pediatr. 2008 Mar;1(3):262. doi: 10.3171/PED/2008/1/3/262.
PubMed 18352776Robertson PL, Muraszko KM, Holmes EJ, Sposto R, Packer RJ, Gajjar A, Dias MS, Allen JC; Children's Oncology Group. Incidence and severity of postoperative cerebellar mutism syndrome in children with medulloblastoma: a prospective study by the Children's Oncology Group. J Neurosurg. 2006 Dec;105(6 Suppl):444-51. doi: 10.3171/ped.2006.105.6.444.
PubMed 17184075Packer RJ, Gajjar A, Vezina G, Rorke-Adams L, Burger PC, Robertson PL, Bayer L, LaFond D, Donahue BR, Marymont MH, Muraszko K, Langston J, Sposto R. Phase III study of craniospinal radiation therapy followed by adjuvant chemotherapy for newly diagnosed average-risk medulloblastoma. J Clin Oncol. 2006 Sep 1;24(25):4202-8. doi: 10.1200/JCO.2006.06.4980.
PubMed 16943538Packer RJ, Gajjar A, Vezina G, et al.: 2340 cGy of craniospinal radiotherapy (CSRT) plus chemotherapy for children with "average-risk" medulloblastoma (MB): a prospective randomized Children's Oncology Group study (A9961). [Abstract] Neuro-Oncology 6 (4): TP-06, 387, 2004.
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase III Prospective Randomized Study of Craniospinal RT Followed by One of Two Adjuvant Chemotherapy Regimens (CCNU, CDDP, VCR OR CPM, CDDP, VCR) for Newly-Diagnosed Average Risk MedulloblastomaMEDULLOBLASTOMA
- ClinicalTrials.gov ID
- NCT00002875
- Acronym / sponsor ID
- A9961
- Conditions
- Brain Tumors, Central Nervous System Tumors
- Keywords
- untreated childhood medulloblastoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 421 participants (actual)
- Lead sponsor
- Children's Oncology GroupResearch network
- Collaborators
- National Cancer Institute (NCI), Pediatric Oncology Group
- Study start
- Dec 1996
- Primary completion
- Feb 2006 (actual)
- Study completion
- Jan 2011 (actual)
- First posted
- 24 May 2004 (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: Radiation therapy uses high energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining radiation therapy with chemotherapy may kill more tumor cells. It is not yet known which chemotherapy regimen is more effective when combined with radiation therapy for treating medulloblastoma.
PURPOSE: Randomized phase III trial to compare two combination chemotherapy treatments plus radiation therapy in treating children with newly diagnosed medulloblastoma.
Detailed description
OBJECTIVES: I. Assess whether a cyclophosphamide-containing combination chemotherapy regimen increases progression-free survival compared to a lomustine-containing regimen in children with newly diagnosed, average-risk medulloblastoma. II. Determine progression-free and overall survival of children treated with craniospinal radiotherapy and local boost radiotherapy for a total dose of 5580 cGy followed by adjuvant lomustine/cisplatin/vincristine vs. cyclophosphamide/cisplatin/vincristine. III. Determine the long-term neurocognitive, endocrinologic, and cardiopulmonary sequelae associated with craniospinal radiotherapy, local boost radiotherapy, and adjuvant chemotherapy in these children, and determine whether replacement of lomustine with cyclophosphamide alters the incidence and degree of sequelae. IV. Determine whether cellular and biologic parameters, including tumor molecular genetic analysis, DNA ploidy, mitotic activity markers, and immunohistochemical analysis, are correlated with progression-free survival, overall survival, and patterns of disease relapse in these patients. V. Evaluate the utility of routine magnetic resonance imaging surveillance studies of the head and spine in detecting subclinical recurrent disease.
OUTLINE: This is a randomized study. Patients are stratified by participating institution. Following surgery, patients are randomized to one of two groups. The first group receives craniospinal irradiation followed by a boost to the primary tumor. Beginning within 1 week after initiation of radiotherapy, patients receive vincristine weekly for 8 doses. Beginning 6 weeks after the completion of radiotherapy, patients receive adjuvant lomustine/vincristine/cisplatin every 6 weeks for a total of 8 courses. The second group receives craniospinal irradiation plus vincristine as above, followed by adjuvant cyclophosphamide/vincristine/cisplatin every 6 weeks for a total of 8 courses. Patients are followed every 3 months for 1 year, every 6 months for 2 years, then annually.
PROJECTED ACCRUAL: It is anticipated that 240-300 patients will be entered over 4 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- Single blind
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Regimen A | Experimental | Biological: filgrastim, Drug: cisplatin, Drug: cyclophosphamide, Drug: lomustine, Drug: mesna, Drug: vincristine sulfate, Radiation: low-LET electron therapy, Radiation: low-LET photon therapyFollowing surgery, craniospinal irradiation followed by a boost to the primary tumor. Beginning within 1 week after initiation of radiotherapy, patients receive vincristine sulfate weekly for 8 doses. Beginning 6 weeks after the completion of radiotherapy, patients receive adjuvant lomustine/vincristine sulfate/cisplatin every 6 weeks for a total of 8 courses. |
| Regimen B | Experimental | Biological: filgrastim, Drug: cisplatin, Drug: cyclophosphamide, Drug: mesna, Drug: vincristine sulfate, Radiation: low-LET electron therapy, Radiation: low-LET photon therapyFollowing surgery, craniospinal irradiation plus vincristine sulfate, followed by adjuvant cyclophosphamide/vincristine sulfate/cisplatin every 6 weeks for a total of 8 courses. |
Who may qualify
- Ages
- 3 to 22 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, 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 |
|---|---|---|
| filgrastimAlso: G-CSF, Neupogen, NSC-614629 | Biological | Regimen A, Regimen B |
| cisplatinAlso: Platinol, NSC-119875 | Drug | Regimen A, Regimen B |
| cyclophosphamideAlso: Cytoxan, NSC-26271 | Drug | Regimen A, Regimen B |
| lomustineAlso: CCNU, NSC-79037 | Drug | Regimen A |
| mesnaAlso: Mesnex, NSC-113891 | Drug | Regimen A, Regimen B |
| vincristine sulfateAlso: Oncovin, NSC-67574 | Drug | Regimen A, Regimen B |
| low-LET electron therapy | Radiation | Regimen A, Regimen B |
| low-LET photon therapy | Radiation | Regimen A, Regimen B |
Primary outcome
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 1 Aug 2014.
- Background: PubMed 18352776Turgut M. Cerebellar mutism. J Neurosurg Pediatr. 2008 Mar;1(3):262. doi: 10.3171/PED/2008/1/3/262.
- Background: PubMed 17184075Robertson PL, Muraszko KM, Holmes EJ, Sposto R, Packer RJ, Gajjar A, Dias MS, Allen JC; Children's Oncology Group. Incidence and severity of postoperative cerebellar mutism syndrome in children with medulloblastoma: a prospective study by the Children's Oncology Group. J Neurosurg. 2006 Dec;105(6 Suppl):444-51. doi: 10.3171/ped.2006.105.6.444.
- Results publication: PubMed 16943538Packer RJ, Gajjar A, Vezina G, Rorke-Adams L, Burger PC, Robertson PL, Bayer L, LaFond D, Donahue BR, Marymont MH, Muraszko K, Langston J, Sposto R. Phase III study of craniospinal radiation therapy followed by adjuvant chemotherapy for newly diagnosed average-risk medulloblastoma. J Clin Oncol. 2006 Sep 1;24(25):4202-8. doi: 10.1200/JCO.2006.06.4980.
- Results publicationPacker RJ, Gajjar A, Vezina G, et al.: 2340 cGy of craniospinal radiotherapy (CSRT) plus chemotherapy for children with "average-risk" medulloblastoma (MB): a prospective randomized Children's Oncology Group study (A9961). [Abstract] Neuro-Oncology 6 (4): TP-06, 387, 2004.
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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.
Roger J. Packer, MD study chair
Children's National Research Institute
Amar Gajjar, MD study chair
St. Jude Children's Research Hospital
41 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing filgrastim, cisplatin and cyclophosphamide in people with Brain Tumors and Central Nervous System Tumors, run by Children's Oncology Group at 41 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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: finished, as of the sponsor's last update on 1 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 41 sites in United States, Canada, Australia, Puerto Rico, Switzerland. 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?
Event Free Survival. 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 NCT00002875, which also lists 4 linked publications.
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 1 Aug 2014.