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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01189266




Registration number
NCT01189266
Ethics application status
Date submitted
25/08/2010
Date registered
26/08/2010
Date last updated
28/10/2021

Titles & IDs
Public title
Vorinostat and Radiation Therapy Followed by Maintenance Therapy With Vorinostat in Treating Younger Patients With Newly Diagnosed Diffuse Intrinsic Pontine Glioma
Scientific title
A Phase 1/2 Study of Suberoylanilide Hydroxamic Acid (SAHA, Vorinostat) and Local Irradiation, Followed by Maintenance SAHA in Children With Newly Diagnosed Diffuse Intrinsic Pontine Gliomas (DIPG)
Secondary ID [1] 0 0
NCI-2011-02600
Secondary ID [2] 0 0
NCI-2011-02600
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anaplastic Astrocytoma 0 0
Anaplastic Oligoastrocytoma 0 0
Diffuse Intrinsic Pontine Glioma 0 0
Gliosarcoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain
Cancer 0 0 0 0
Children's - Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - 3-Dimensional Conformal Radiation Therapy
Treatment: Other - Intensity-Modulated Radiation Therapy
Other interventions - Laboratory Biomarker Analysis
Treatment: Drugs - Vorinostat

Experimental: Arm 1 Phase I Vorinostat 180 mg/m^2 - Patients in phase I received vorinostat at 180 mg/m\^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m\^2/day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Experimental: Arm 2 Phase 1 Vorinostat 230 mg/m^2 - Patients received a higher dose of vorinostat at 230 mg/m\^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m\^2/day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Experimental: Arm 3 Phase II Evaluation Vorinostat 230 mg/m^2 - Patients received a higher dose of vorinostat at 230 mg/m\^2/day PO on Monday through Friday weekly for the duration of radiation therapy (6-7 weeks). Patients underwent 3D conformal or intensity-modulated radiation therapy 5 days per week for 6 weeks. After completing concurrent vorinostat and radiation therapy, patients then received maintenance therapy comprising of vorinostat at 230 mg/m\^2/ day PO on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.


Treatment: Other: 3-Dimensional Conformal Radiation Therapy
Undergo 3D conformal radiation therapy

Treatment: Other: Intensity-Modulated Radiation Therapy
Undergo intensity-modulated radiation therapy

Other interventions: Laboratory Biomarker Analysis
Correlative studies

Treatment: Drugs: Vorinostat
Given PO
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Other interventions
Intervention code [3] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Maximum Tolerated Dose (MTD) of Vorinostat
Timepoint [1] 0 0
Planned 7 weeks during chemoradiotherapy
Primary outcome [2] 0 0
Event-Free Survival
Timepoint [2] 0 0
2 years after study enrollment
Primary outcome [3] 0 0
Incidence of Toxicity During Chemoradiation Therapy
Timepoint [3] 0 0
Planned 7 weeks during chemoradiotherapy
Primary outcome [4] 0 0
Incidence of Toxicity During Maintenance Therapy
Timepoint [4] 0 0
Planned 12 months of maintenance with Vorinostat
Secondary outcome [1] 0 0
Overall Survival
Timepoint [1] 0 0
2 years after study enrollment
Secondary outcome [2] 0 0
Change in H3 and H4 Acetylation Levels in PBMCs
Timepoint [2] 0 0
Baseline to up to 7 weeks
Secondary outcome [3] 0 0
Change in NHEJ Activity in PBMCs
Timepoint [3] 0 0
Baseline to up to 7 weeks
Secondary outcome [4] 0 0
Levels of DNA Repair Proteins in Paraffin-embedded Blocks, Measured Via Immunohistochemistry or Western Analysis
Timepoint [4] 0 0
Baseline

Eligibility
Key inclusion criteria
* Patients with newly diagnosed diffuse intrinsic pontine gliomas (DIPGs), defined as tumors with a pontine epicenter and diffuse involvement of at least 2/3 of the pons, are eligible without histologic confirmation; patients with brainstem tumors that do not meet these criteria or not considered to be typical intrinsic pontine gliomas will only be eligible if the tumors are biopsied and proven to be an anaplastic astrocytoma, glioblastoma multiforme, gliosarcoma, or anaplastic mixed glioma; patients with juvenile pilocytic astrocytoma, fibrillary astrocytoma, gangliogliomas, or other mixed gliomas without anaplasia are not eligible; patients with disseminated disease are not eligible, and magnetic resonance imaging (MRI) of spine must be performed if disseminated disease is suspected by the treating physician
* Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
* Patients must not have received any prior treatment except dexamethasone and/or surgery
* Peripheral absolute neutrophil count (ANC) >= 1000/uL
* Platelet count >= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment)
* Hemoglobin >= 8.0 g/dL (may receive red blood cell [RBC] transfusions)
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70ml/min/1.73 m^2 or a serum creatinine based on age/gender as follows:

* 0.8 mg/dL (3 to < 6 years of age)
* 1 mg/dL (6 to < 10 years of age)
* 1.2 mg/dL (10 to < 13 years of age)
* 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)
* 1.7 mg/dL (male) or 1.4 mg/dL (female) (>= 16 years of age)
* Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age
* Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 110 U/L; for the purpose of this study, the ULN for SGPT (ALT) is 45 U/L
* Serum albumin >= 2 g/dL
* Patients with seizure disorder may be enrolled if on non-enzyme inducing anticonvulsants (with the exception of valproic acid) and seizures are well controlled
* Patients must be able to swallow capsules or liquids; patients dependent on nasogastric (NG) tube feeding are not permitted to receive protocol therapy
* Enrollment must be no later than 28 days after the date of radiographic diagnosis or surgery, whichever is the later date
Minimum age
37 Months
Maximum age
21 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Pregnant or breast-feeding women will not be entered on this study; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
* Growth factors that support platelet or white cell number or function must not have been administered within the 7 days prior to enrollment
* Patients who are currently receiving another investigational drug are not eligible
* Patients who are currently receiving other anti-cancer agents are not eligible
* Patients must not currently be receiving enzyme inducing anticonvulsants
* Patients on valproic acid must discontinue valproic acid for at least 2 weeks before starting protocol therapy
* Patients receiving coumadin, heparin, low-molecular weight heparin, or any other anti-coagulants are not eligible for study entry
* Patients receiving acetylsalicylic acid (ASA) (> 81 mg/day), non-steroidal anti-inflammatory drugs, clopidogrel (Plavix), dipyridamole (Persantine), or any other drug that inhibits platelet function are not eligible for study entry
* Patients who have an uncontrolled infection are not eligible
* Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
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
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
9/08/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/09/2021
Sample size
Target
Accrual to date
Final
79
Recruitment in Australia
Recruitment state(s)
QLD,WA
Recruitment hospital [1] 0 0
Royal Children's Hospital-Brisbane - Herston
Recruitment hospital [2] 0 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [3] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
4029 - Herston
Recruitment postcode(s) [2] 0 0
4101 - South Brisbane
Recruitment postcode(s) [3] 0 0
6008 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
Delaware
Country [7] 0 0
United States of America
State/province [7] 0 0
District of Columbia
Country [8] 0 0
United States of America
State/province [8] 0 0
Florida
Country [9] 0 0
United States of America
State/province [9] 0 0
Georgia
Country [10] 0 0
United States of America
State/province [10] 0 0
Hawaii
Country [11] 0 0
United States of America
State/province [11] 0 0
Idaho
Country [12] 0 0
United States of America
State/province [12] 0 0
Illinois
Country [13] 0 0
United States of America
State/province [13] 0 0
Indiana
Country [14] 0 0
United States of America
State/province [14] 0 0
Iowa
Country [15] 0 0
United States of America
State/province [15] 0 0
Kentucky
Country [16] 0 0
United States of America
State/province [16] 0 0
Massachusetts
Country [17] 0 0
United States of America
State/province [17] 0 0
Michigan
Country [18] 0 0
United States of America
State/province [18] 0 0
Minnesota
Country [19] 0 0
United States of America
State/province [19] 0 0
Mississippi
Country [20] 0 0
United States of America
State/province [20] 0 0
Missouri
Country [21] 0 0
United States of America
State/province [21] 0 0
Montana
Country [22] 0 0
United States of America
State/province [22] 0 0
Nebraska
Country [23] 0 0
United States of America
State/province [23] 0 0
New Jersey
Country [24] 0 0
United States of America
State/province [24] 0 0
New Mexico
Country [25] 0 0
United States of America
State/province [25] 0 0
New York
Country [26] 0 0
United States of America
State/province [26] 0 0
North Carolina
Country [27] 0 0
United States of America
State/province [27] 0 0
Ohio
Country [28] 0 0
United States of America
State/province [28] 0 0
Oregon
Country [29] 0 0
United States of America
State/province [29] 0 0
Pennsylvania
Country [30] 0 0
United States of America
State/province [30] 0 0
South Carolina
Country [31] 0 0
United States of America
State/province [31] 0 0
Tennessee
Country [32] 0 0
United States of America
State/province [32] 0 0
Texas
Country [33] 0 0
United States of America
State/province [33] 0 0
Utah
Country [34] 0 0
United States of America
State/province [34] 0 0
Virginia
Country [35] 0 0
United States of America
State/province [35] 0 0
Washington
Country [36] 0 0
United States of America
State/province [36] 0 0
Wisconsin
Country [37] 0 0
United States of America
State/province [37] 0 0
Wyoming
Country [38] 0 0
Canada
State/province [38] 0 0
Ontario
Country [39] 0 0
Canada
State/province [39] 0 0
Quebec

Funding & Sponsors
Primary sponsor type
Government body
Name
National Cancer Institute (NCI)
Address
Country

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Jack M Su
Address 0 0
Children's Oncology Group
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?

TypeOther DetailsAttachment
Study protocol Study Protocol and Statistical Analysis Plan https://cdn.clinicaltrials.gov/large-docs/66/NCT01189266/Prot_SAP_000.pdf
Statistical analysis plan Study Protocol and Statistical Analysis Plan https://cdn.clinicaltrials.gov/large-docs/66/NCT01189266/Prot_SAP_000.pdf
Study protocol Study Protocol and Statistical Analysis Plan https://cdn.clinicaltrials.gov/large-docs/66/NCT01189266/Prot_SAP_000.pdf
Statistical analysis plan Study Protocol and Statistical Analysis Plan https://cdn.clinicaltrials.gov/large-docs/66/NCT01189266/Prot_SAP_000.pdf
Study protocol Study Protocol and Statistical Analysis Plan https://cdn.clinicaltrials.gov/large-docs/66/NCT01189266/Prot_SAP_000.pdf
Statistical analysis plan Study Protocol and Statistical Analysis Plan https://cdn.clinicaltrials.gov/large-docs/66/NCT01189266/Prot_SAP_000.pdf



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT01189266