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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01878617




Registration number
NCT01878617
Ethics application status
Date submitted
10/06/2013
Date registered
17/06/2013
Date last updated
18/01/2024

Titles & IDs
Public title
A Clinical and Molecular Risk-Directed Therapy for Newly Diagnosed Medulloblastoma
Scientific title
A Clinical and Molecular Risk-Directed Therapy for Newly Diagnosed Medulloblastoma
Secondary ID [1] 0 0
NCI-2013-01125
Secondary ID [2] 0 0
SJMB12
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Medulloblastoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Children's - Brain
Cancer 0 0 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Craniospinal Irradiation with boost to the primary tumor site
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Cisplatin
Treatment: Drugs - Vincristine
Treatment: Drugs - Vismodegib
Treatment: Drugs - Pemetrexed
Treatment: Drugs - Gemcitabine

Experimental: Stratum W1: Low Risk - Participants in stratum W1 will undergo reduced dose Craniospinal Irradiation with boost to the primary tumor site once daily 5 days a week for 6 weeks. Six weeks after completion of radiotherapy, patients receive one cycle of chemotherapy (cisplatin, vincristine, cyclophosphamide) once every 4 weeks for 4 cycles in absence of unacceptable toxicity. Some participants will complete aerobic training and/or neurocognitive remediation.

Experimental: Stratum W2: Atypical - Participants in stratum W2 will undergo standard dose craniospinal radiation with boost to the primary tumor site once daily 5 days a week for 6 weeks. Six weeks after completion of radiotherapy, patients receive one cycle of chemotherapy (cisplatin, vincristine, cyclophosphamide) once every 4 weeks for 4 cycles in absence of unacceptable toxicity. Some participants will complete aerobic training and/or neurocognitive remediation.

Experimental: Stratum W3: High Risk - Participants in stratum W3 will undergo high dose craniospinal radiation with boost to the primary tumor site once daily 5 days a week for 6 weeks. Six weeks after completion of radiotherapy, patients receive one cycle of chemotherapy (cisplatin, vincristine, cyclophosphamide) once every 4 weeks for 4 cycles in absence of unacceptable toxicity. Some participants will complete aerobic training and/or neurocognitive remediation.

Experimental: Stratum S1: Standard Risk - Participants in stratum S1 will undergo standard dose craniospinal radiation with boost to the primary tumor site once daily 5 days a week for 6 weeks. Six weeks after completion of radiotherapy, patients receive one cycle of chemotherapy (cisplatin, vincristine, cyclophosphamide) once every 4 weeks for 4 cycles in absence of unacceptable toxicity. After completion of 4 cycles of chemotherapy, participants who are skeletally mature will receive maintenance chemotherapy with vismodegib. Some participants will complete aerobic training and/or neurocognitive remediation.

Experimental: Stratum S2: High Risk - Participants in stratum S2 will undergo high dose craniospinal radiation with boost to the primary tumor site once daily 5 days a week for 6 weeks. Six weeks after completion of radiotherapy, patients receive one cycle of chemotherapy (cisplatin, vincristine, cyclophosphamide) once every 4 weeks for 4 cycles in absence of unacceptable toxicity. After completion of 4 cycles of chemotherapy, participants who are skeletally mature will receive maintenance chemotherapy with vismodegib. Some participants will complete aerobic training and/or neurocognitive remediation.

Experimental: Stratum N1: Standard Risk - Participants in stratum N1 will undergo standard dose craniospinal radiation with boost to the primary tumor site once daily 5 days a week for 6 weeks. Six weeks after completion of radiotherapy, patients receive one cycle of chemotherapy (cisplatin, vincristine, cyclophosphamide) once every 4 weeks for 4 cycles in absence of unacceptable toxicity. Some participants will complete aerobic training and/or neurocognitive remediation.

Experimental: Stratum N2: Intermediate Risk - Participants in stratum N2 will undergo standard dose craniospinal radiation with boost to the primary tumor site once daily 5 days a week for 6 weeks. Six weeks after completion of radiotherapy, patients receive standard chemotherapy (cisplatin, vincristine, cyclophosphamide) for 4 cycles intermixed with an additional 3 cycles of chemotherapy with pemetrexed and gemcitabine in absence of unacceptable toxicity. Some participants will complete aerobic training and/or neurocognitive remediation.

Experimental: Stratum N3: High Risk - Participants in stratum N3 will undergo high dose craniospinal radiation with boost to the primary tumor site once daily 5 days a week for 6 weeks. Six weeks after completion of radiotherapy, patients receive standard chemotherapy (cisplatin, vincristine, cyclophosphamide) for 4 cycles intermixed with an additional 3 cycles of chemotherapy with pemetrexed and gemcitabine in absence of unacceptable toxicity. Some participants will complete aerobic training and/or neurocognitive remediation.


Treatment: Other: Craniospinal Irradiation with boost to the primary tumor site
All participants will undergo craniospinal irradiation (CSI) with boost to the primary tumor site. The dose given is based on the molecular and risk group as noted in the arm descriptions. The type of radiation used includes conformal radiation therapy (photons) or intensity modulated radiation therapy (IMRT) or proton beam therapy.

Treatment: Drugs: Cyclophosphamide
Route of Administration (ROA): Intravenously (IV)

Treatment: Drugs: Cisplatin
ROA: IV

Treatment: Drugs: Vincristine
ROA: IV

Treatment: Drugs: Vismodegib
ROA: Orally (PO)

Treatment: Drugs: Pemetrexed
ROA: IV

Treatment: Drugs: Gemcitabine
ROA: IV
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival in Stratum W1
Timepoint [1] 0 0
2 years after diagnosis
Primary outcome [2] 0 0
Progression-free Survival in Stratum N1
Timepoint [2] 0 0
2 years after diagnosis
Primary outcome [3] 0 0
Progression-free Survival in Stratum S1 Skeletally Mature Cohort
Timepoint [3] 0 0
2 years after diagnosis
Primary outcome [4] 0 0
Change in VO2 Peak Value
Timepoint [4] 0 0
baseline and 12 weeks post-randomization
Primary outcome [5] 0 0
Change in Spatial Span Backward Standard Score
Timepoint [5] 0 0
baseline and 10-12 weeks post baseline
Secondary outcome [1] 0 0
Progression-free Survival in Stratum W1 Compared to Historical Controls
Timepoint [1] 0 0
2 years after diagnosis
Secondary outcome [2] 0 0
Overall Survival in Stratum W1
Timepoint [2] 0 0
2 years after diagnosis
Secondary outcome [3] 0 0
Progression-free Survival in Stratum S1 Skeletally Immature Cohort
Timepoint [3] 0 0
2 years after diagnosis
Secondary outcome [4] 0 0
Progression-free Survival in Stratum S2 Skeletally Mature Cohort
Timepoint [4] 0 0
2 years after diagnosis
Secondary outcome [5] 0 0
Progression-free Survival in Stratum S2 Skeletally Immature Cohort
Timepoint [5] 0 0
2 years after diagnosis
Secondary outcome [6] 0 0
Overall Survival in Stratum S1 Skeletally Mature Cohort
Timepoint [6] 0 0
2 years after diagnosis
Secondary outcome [7] 0 0
Overall Survival in Stratum S1 Skeletally Immature Cohort
Timepoint [7] 0 0
2 years after diagnosis
Secondary outcome [8] 0 0
Overall Survival in Stratum S2 Skeletally Mature Cohort
Timepoint [8] 0 0
2 years after diagnosis
Secondary outcome [9] 0 0
Overall Survival in Stratum S2 Skeletally Immature Cohort
Timepoint [9] 0 0
2 years after diagnosis
Secondary outcome [10] 0 0
Progression-free Survival in Stratum N2
Timepoint [10] 0 0
2 years after diagnosis
Secondary outcome [11] 0 0
Overall Survival in Stratum N2
Timepoint [11] 0 0
2 years after diagnosis
Secondary outcome [12] 0 0
Progression-free Survival in Stratum N3
Timepoint [12] 0 0
2 years after diagnosis
Secondary outcome [13] 0 0
Overall Survival in Stratum N3
Timepoint [13] 0 0
2 years after diagnosis
Secondary outcome [14] 0 0
Progression-free Survival in Stratum N1 Compared to Historical Controls
Timepoint [14] 0 0
2 years after diagnosis
Secondary outcome [15] 0 0
Overall Survival in Stratum N1
Timepoint [15] 0 0
2 years after diagnosis
Secondary outcome [16] 0 0
Percentage of Participants Who Complete Pemetrexed and Gemcitabine Therapy
Timepoint [16] 0 0
10 months after on treatment
Secondary outcome [17] 0 0
Percentage of Participants Who Complete Vismodegib Therapy
Timepoint [17] 0 0
20 months after on treatment
Secondary outcome [18] 0 0
Number of Local Failures
Timepoint [18] 0 0
2 and 5 years after on treatment
Secondary outcome [19] 0 0
Change in hand grip strength
Timepoint [19] 0 0
Baseline (at enrollment), 12 weeks, at end of adjuvant chemotherapy (28 weeks for strata W1/W2/W3/N1/S1/S2 and 40 weeks for strata N2/N3), and 1, 2, and 5 years after the last patient enrollment
Secondary outcome [20] 0 0
Change in range of motion
Timepoint [20] 0 0
Baseline (at enrollment), 12 weeks, at end of adjuvant chemotherapy (28 weeks for strata W1/W2/W3/N1/S1/S2 and 40 weeks for strata N2/N3), and 1, 2, and 5 years after the last patient enrollment
Secondary outcome [21] 0 0
Change in overall flexibility
Timepoint [21] 0 0
Baseline (at enrollment), 12 weeks, at end of adjuvant chemotherapy (28 weeks for strata W1/W2/W3/N1/S1/S2 and 40 weeks for strata N2/N3), and 1, 2, and 5 years after the last patient enrollment
Secondary outcome [22] 0 0
Change in motor proficiency
Timepoint [22] 0 0
Baseline (at enrollment), 12 weeks, at end of adjuvant chemotherapy (28 weeks for strata W1/W2/W3/N1/S1/S2 and 40 weeks for strata N2/N3), and 1, 2, and 5 years after the last patient enrollment
Secondary outcome [23] 0 0
Change in quality of life (QOL) score
Timepoint [23] 0 0
Baseline (at enrollment), 12 weeks, at end of adjuvant chemotherapy (28 weeks for strata W1/W2/W3/N1/S1/S2 and 40 weeks for strata N2/N3), and 1, 2, and 5 years after the last patient enrollment
Secondary outcome [24] 0 0
Change in fatigue score
Timepoint [24] 0 0
Baseline (at enrollment), 12 weeks, at end of adjuvant chemotherapy (28 weeks for strata W1/W2/W3/N1/S1/S2 and 40 weeks for strata N2/N3), and 1, 2, and 5 years after the last patient enrollment
Secondary outcome [25] 0 0
Change in measure of memory function
Timepoint [25] 0 0
Baseline (at enrollment), 12 weeks, and at end of adjuvant chemotherapy (28 weeks for strata W1/W2/W3/N1/S1/S2 and 40 weeks for strata N2/N3).
Secondary outcome [26] 0 0
Change in measure of attention
Timepoint [26] 0 0
Baseline (at enrollment), 12 weeks, and at end of adjuvant chemotherapy (28 weeks for strata W1/W2/W3/N1/S1/S2 and 40 weeks for strata N2/N3).
Secondary outcome [27] 0 0
Change in executive function score
Timepoint [27] 0 0
Baseline (at enrollment), 12 weeks, and at end of adjuvant chemotherapy (28 weeks for strata W1/W2/W3/N1/S1/S2 and 40 weeks for strata N2/N3).
Secondary outcome [28] 0 0
Change in sleep
Timepoint [28] 0 0
Baseline and 10-12 weeks post randomization
Secondary outcome [29] 0 0
Association between baseline cognitive performance and sleep quality
Timepoint [29] 0 0
Baseline and approximately 7-10 months after treatment
Secondary outcome [30] 0 0
Association between baseline cognitive performance and sleep quantity
Timepoint [30] 0 0
Baseline and approximately 7-10 months after treatment
Secondary outcome [31] 0 0
Association between baseline cognitive performance and fatigue
Timepoint [31] 0 0
Baseline and approximately 7-10 months after treatment
Secondary outcome [32] 0 0
Longitudinal change in measure of intellectual function
Timepoint [32] 0 0
Baseline through 5 years after enrollment
Secondary outcome [33] 0 0
Association of demographic and clinical factors with change in intellectual function
Timepoint [33] 0 0
Baseline through 5 years after enrollment
Secondary outcome [34] 0 0
Longitudinal change in measure of academic ability
Timepoint [34] 0 0
Baseline through 5 years after enrollment
Secondary outcome [35] 0 0
Association of demographic and clinical factors with change in academic ability
Timepoint [35] 0 0
Baseline through 5 years after enrollment
Secondary outcome [36] 0 0
Longitudinal change in measure of attention
Timepoint [36] 0 0
Baseline through 5 years after enrollment
Secondary outcome [37] 0 0
Association of demographic and clinical factors with change in attention
Timepoint [37] 0 0
Baseline through 5 years after enrollment
Secondary outcome [38] 0 0
Longitudinal change in measure of memory
Timepoint [38] 0 0
Baseline through 5 years after enrollment
Secondary outcome [39] 0 0
Association of demographic and clinical factors with change in memory
Timepoint [39] 0 0
Baseline through 5 years after enrollment
Secondary outcome [40] 0 0
Longitudinal change in measure of cognitive processing speed function
Timepoint [40] 0 0
Baseline through 5 years after enrollment
Secondary outcome [41] 0 0
Association of demographic and clinical factors with change in cognitive processing speed
Timepoint [41] 0 0
Baseline through 5 years after enrollment
Secondary outcome [42] 0 0
Longitudinal change in measure of neurocognitive executive function
Timepoint [42] 0 0
Baseline through 5 years after enrollment
Secondary outcome [43] 0 0
Association of demographic and clinical factors with change in neurocognitive executive function
Timepoint [43] 0 0
Baseline through 5 years after enrollment
Secondary outcome [44] 0 0
Change in measure of attention
Timepoint [44] 0 0
Baseline (at 7-10 months after start of therapy) and at 3 months after baseline
Secondary outcome [45] 0 0
Change in measure of processing speed
Timepoint [45] 0 0
Baseline (at 7-10 months after start of therapy) and at 3 months after baseline
Secondary outcome [46] 0 0
Change in measure of executive function ability
Timepoint [46] 0 0
Baseline (at 7-10 months after start of therapy) and at 3 months after baseline
Secondary outcome [47] 0 0
Change in measure of attention among 3 groups (working memory intervention + physical exercise intervention VS. working memory intervention alone VS. physical training intervention alone)
Timepoint [47] 0 0
Baseline and at 3 months after baseline
Secondary outcome [48] 0 0
Change in measure of processing speed among 3 groups (working memory intervention + physical exercise intervention VS. working memory intervention alone VS. physical training intervention alone)
Timepoint [48] 0 0
Baseline and at 3 months after baseline
Secondary outcome [49] 0 0
Change in measure of executive function among 3 groups (working memory intervention + physical exercise intervention VS. working memory intervention alone VS. physical training intervention alone)
Timepoint [49] 0 0
Baseline and at 3 months after baseline
Secondary outcome [50] 0 0
Change in measure of attention between participants who received computer-based intervention VS. those who did not
Timepoint [50] 0 0
Baseline (at 7-10 months after on treatment) through 6 months after baseline.
Secondary outcome [51] 0 0
Change in measure of working memory between participants who received computer-based intervention VS. those who did not
Timepoint [51] 0 0
Baseline (at 7-10 months after on treatment) through 6 months after baseline.
Secondary outcome [52] 0 0
Change in measure of processing speed between participants who received computer-based intervention VS. those who did not
Timepoint [52] 0 0
Baseline (at 7-10 months after on treatment) through 6 months after baseline.
Secondary outcome [53] 0 0
Change in measure of executive function between participants who received computer-based intervention VS. those who did not
Timepoint [53] 0 0
Baseline (at 7-10 months after on treatment) through 6 months after baseline.

Eligibility
Key inclusion criteria
INCLUSION CRITERIA

* Medulloblastoma or medulloblastoma variants including posterior fossa PNET as documented by an institutional pathologist.
* Participant's age meets one of the following: (1) Age greater than or equal to 3 years and less than 22 years of age at the time of diagnosis (may enroll on Strata W, S or N), OR (2) age is greater than or equal to 22 years and less than 40 years AND patient has SHH medulloblastoma (must enroll on Stratum S).
* No previous radiotherapy, chemotherapy or other brain tumor directed therapy other than corticosteroid therapy and surgery.
* Patients must begin treatment as outlined in the protocol within 36 days of definitive surgery (day of surgery is day 0; definitive surgery includes second surgeries to resect residual tumor).
* Adequate performance status: children < 10-Lansky Score = 30; children = 10-Karnofsky = 30 (except for posterior fossa syndrome).
* Females of child-bearing potential cannot be pregnant or breast-feeding. Female participants > 10 years of age or post-menarche must have a negative serum or urine pregnancy test prior to enrollment.
* Biological parent(s) of participant (child) enrolling on this protocol. These parents will be assigned to cohort P. The exclusion criteria below do not apply to this cohort.

EXCLUSION CRITERIA

* CNS embryonal tumor other than medulloblastoma or PNET in the posterior fossa, for example, patients with diagnosis of Atypical Teratoid / Rhabdoid Tumor (ATRT), supratentorial PNET, pineoblastoma, ependymoblastoma, ETANTR are excluded.
* Research participants with other clinically significant medical disorders that could compromise their ability to tolerate protocol therapy or would interfere with the study procedures or results history.

Participants in the Stratum S maintenance chemotherapy portion of the study must meet the criteria below prior to start of vismodegib therapy:

* Participants must be Stratum S (SHH)
* Participants must be skeletally mature defined as females with a bone age = 15 years and males with a bone age = 17 years.
* Must be able to swallow pills
* BSA must be >0.67 and <2.5 m2
* Male and female participants of reproductive potential must agree to effective contraception during and after study treatment. See Appendices I and II for further guidance for participants receiving vismodegib
* ANC = 1000/mm^3 (after G-CSF discontinued)
* Platelets = 50,000/mm^3 (without support)
* Hgb = 8 g/dL (with or without transfusion support)
* Serum creatinine = 1.5 mg/dL
* Total bilirubin = 1.5X the institutional ULN
* SGPT (ALT) = 2.5X the institutional ULN
* SGOT (AST) = 2.5X the institutional ULN
* Alkaline Phosphatase = 1.5X the institutional ULN
* Serum albumin = 2.5 g/dL

Participants in the exercise intervention portion of the study must meet all criteria below:

* Must be = 5 years and < 22 years at the time of enrollment
* Must have no congenital heart disease
* Must be capable of performing the exercise intervention at the time of baseline assessment as determined by the treating physician.

Participants in the cognitive remediation intervention portion of the study must meet all criteria below:

* Completed protocol-directed radiation therapy
* =5 years at the time of remediation intervention consent or age is greater than or equal to 22 years and less than 40 years and patient has SHH medulloblastoma
* English as primary language and training aide who speaks English available to participate in required sessions
* No significant cognitive impairment operationalized as either an IQ < 70 for children with St. Jude SJMB12 study baseline testing or based on clinician judgment baseline IQ missing
* No major sensory or motor impairment that would preclude valid cognitive testing (e.g., unresolved posterior fossa syndrome, blindness, poorly controlled seizures/photosensitive epilepsy, psychosis) or a major psychological condition that would preclude completion of the intervention (e.g., significant oppositionality, autism spectrum disorder, severe anxiety or depressive symptoms)
Minimum age
3 Years
Maximum age
39 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
23/06/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/01/2028
Actual
Sample size
Target
Accrual to date
Final
660
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Sydney Children's Hospital - Randwick
Recruitment hospital [2] 0 0
Children's Hospital at Westmead - Westmead
Recruitment hospital [3] 0 0
Queensland Children's Hospital - Brisbane
Recruitment hospital [4] 0 0
Royal Children's Hospital, Melbourne - Melbourne
Recruitment hospital [5] 0 0
Perth Children's Hospital - Perth
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4029 - Brisbane
Recruitment postcode(s) [4] 0 0
3052 - Melbourne
Recruitment postcode(s) [5] 0 0
6008 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
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
Minnesota
Country [6] 0 0
United States of America
State/province [6] 0 0
North Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
South Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Tennessee
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
Canada
State/province [11] 0 0
Alberta
Country [12] 0 0
Canada
State/province [12] 0 0
Ontario
Country [13] 0 0
Canada
State/province [13] 0 0
Quebec
Country [14] 0 0
New Zealand
State/province [14] 0 0
Auckland

Funding & Sponsors
Primary sponsor type
Other
Name
St. Jude Children's Research Hospital
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Genentech, Inc.
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Government body
Name [2] 0 0
National Cancer Institute (NCI)
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Amar Gajjar, MD
Address 0 0
St. Jude Children's Research Hospital
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT01878617