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Veliparib, Radiation Therapy, and Temozolomide in Treating Patients With Newly Diagnosed Malignant Glioma Without H3 K27M or BRAFV600 Mutations

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ClinicalTrials.gov Identifier: NCT03581292
Recruitment Status : Active, not recruiting
First Posted : July 10, 2018
Results First Posted : April 23, 2024
Last Update Posted : May 20, 2024
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Anaplastic Astrocytoma
Glioblastoma
Malignant Glioma
Interventions Radiation: Radiation Therapy
Drug: Temozolomide
Drug: Veliparib
Enrollment 38
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Stratum 1 Stratum 2
Hide Arm/Group Description Pediatric newly-diagnosed HGG patients who are wild-type with respect to H3 K27M, BRAF, and IDH1/2 Pediatric newly-diagnosed HGG patients who are positive for either IDH1/2 mutation
Period Title: Overall Study
Started 24 14
Completed 11 9
Not Completed 13 5
Reason Not Completed
Physician Decision             9             5
Withdrawal by Subject             3             0
Withdrawal before Therapy Start             1             0
Arm/Group Title Stratum 1 Stratum 2 Total
Hide Arm/Group Description Pediatric newly-diagnosed HGG patients who are wild-type with respect to H3 K27M, BRAF, and IDH1/2 Pediatric newly-diagnosed HGG patients who are positive for either IDH1/2 mutation Total of all reporting groups
Overall Number of Baseline Participants 24 14 38
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 14 participants 38 participants
<=18 years
23
  95.8%
6
  42.9%
29
  76.3%
Between 18 and 65 years
1
   4.2%
8
  57.1%
9
  23.7%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 24 participants 14 participants 38 participants
12.2  (4) 18.4  (2.9) 14.5  (4.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 14 participants 38 participants
Female
4
  16.7%
8
  57.1%
12
  31.6%
Male
20
  83.3%
6
  42.9%
26
  68.4%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 14 participants 38 participants
Hispanic or Latino
1
   4.2%
2
  14.3%
3
   7.9%
Not Hispanic or Latino
19
  79.2%
12
  85.7%
31
  81.6%
Unknown or Not Reported
4
  16.7%
0
   0.0%
4
  10.5%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 14 participants 38 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
2
   8.3%
0
   0.0%
2
   5.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
16
  66.7%
13
  92.9%
29
  76.3%
More than one race
2
   8.3%
0
   0.0%
2
   5.3%
Unknown or Not Reported
4
  16.7%
1
   7.1%
5
  13.2%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 24 participants 14 participants 38 participants
24 14 38
1.Primary Outcome
Title Event Free Survival (EFS)
Hide Description Compare event free survival to historical data for each stratum. Analysis will be based on a 2-sample, 1 sided logrank test. EFS is measured from time of enrollment to the date of first documented progression, second malignancy, or date of death from any cause, whichever comes first. Subjects who do not have any event will be censored at the last follow-up date.
Time Frame Up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received study therapy will be included in the analysis.
Arm/Group Title Stratum 1 Stratum 2
Hide Arm/Group Description:
Pediatric newly-diagnosed HGG patients who are wild-type with respect to H3 K27M, BRAF, and IDH1/2
Pediatric newly-diagnosed HGG patients who are positive for either IDH1/2 mutation
Overall Number of Participants Analyzed 23 14
Measure Type: Number
Unit of Measure: probability
0.9857 0.9571
2.Secondary Outcome
Title Objective Response
Hide Description Estimate the objective response rate in patients with measurable disease. The 95% confidence interval will be calculated by Clopper-Pearson method. Objective responses are defined as patients who achieved complete response or partial response anytime during treatment. Tumor response criteria are determined by changes in size using the longest tumor dimension, and its perpendicular. Either T1, T2 weighted/FLAIR images are used - whichever gives the best estimate of tumor size. Complete Response (CR): Disappearance of all target lesions; Partial response (PR): >=50% decrease in the sum of the products of the two perpendicular diameters of target lesions, compared to baseline measurement. Objective Response = CR + PR.
Time Frame Anytime during treatment (up to 1 year from enrollment)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who had measurable disease at baseline and received study therapy will be included in the analysis.
Arm/Group Title Stratum 1 Stratum 2
Hide Arm/Group Description:
Pediatric newly-diagnosed HGG patients who are wild-type with respect to H3 K27M, BRAF, and IDH1/2
Pediatric newly-diagnosed HGG patients who are positive for either IDH1/2 mutation
Overall Number of Participants Analyzed 11 7
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
9.1
(0.2 to 41.3)
14.3
(0.4 to 57.9)
3.Secondary Outcome
Title Overall Survival (OS)
Hide Description The Kaplan-Meier method will be used to estimate the 2-year overall survival for each stratum. OS is measured from time of enrollment to the date of death from any cause. Subjects who do not have any event will be censored at the last follow-up date.
Time Frame Up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received study therapy will be included in the analysis.
Arm/Group Title Stratum 1 Stratum 2
Hide Arm/Group Description:
Pediatric newly-diagnosed HGG patients who are wild-type with respect to H3 K27M, BRAF, and IDH1/2
Pediatric newly-diagnosed HGG patients who are positive for either IDH1/2 mutation
Overall Number of Participants Analyzed 23 14
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: survival probability of patients
0.27
(0.11 to 0.46)
0.85
(0.52 to 0.96)
4.Other Pre-specified Outcome
Title Biomarker Analysis
Hide Description Will provide a frequency table summarizing the number of patients with each aberration/alteration detected in germline and/or tumor samples. For longitudinal plasma samples used to assess circulating tumor deoxyribonucleic acid, will summarize the percentage of patients with samples as well as display/summarize any changes in molecular markers. When feasible we will explore the association of these aberrations with EFS/OS and objective response rates via Cox models and fisher exact tests, respectively. Will also explore associations between genetic variants and clinical/demographic variables including age, resection status, histology, etc. For analyses exploring associations of a large number of potential markers with clinical outcome, will utilize false discovery rate approaches in order to control family-wise error rate.
Time Frame Up to 5.5 years
Outcome Measure Data Not Reported
Time Frame Enrollment up to 3 years after enrollment
Adverse Event Reporting Description Adverse event reporting is collected routinely using case report forms. The SAE table reflects NCI Common Terminology Criteria for Adverse Events (CTCAEs) submitted by the institution via expedited reporting (NCI AdEERs / CAeRs). All remaining CTCAEs collected by means other than expedited reporting are non-serious and are reported in the "AE Other" table. All-Cause Mortality includes all deaths collected on the study. Ineligible patients are excluded from reporting of adverse events.
 
Arm/Group Title Stratum 1 Stratum 2
Hide Arm/Group Description Pediatric newly-diagnosed HGG patients who are wild-type with respect to H3 K27M, BRAF, and IDH1/2 Pediatric newly-diagnosed HGG patients who are positive for either IDH1/2 mutation
All-Cause Mortality
Stratum 1 Stratum 2
Affected / at Risk (%) Affected / at Risk (%)
Total   18/23 (78.26%)      3/14 (21.43%)    
Hide Serious Adverse Events
Stratum 1 Stratum 2
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   22/23 (95.65%)      5/14 (35.71%)    
General disorders     
Death NOS †  1/23 (4.35%)  1 0/14 (0.00%)  0
Disease progression †  16/23 (69.57%)  16 2/14 (14.29%)  2
Fatigue †  0/23 (0.00%)  0 1/14 (7.14%)  1
Gait disturbance †  1/23 (4.35%)  1 0/14 (0.00%)  0
Infections and infestations     
Lung infection †  1/23 (4.35%)  1 0/14 (0.00%)  0
Urinary tract infection †  1/23 (4.35%)  1 0/14 (0.00%)  0
Investigations     
Lymphocyte count decreased †  0/23 (0.00%)  0 1/14 (7.14%)  1
Neutrophil count decreased †  2/23 (8.70%)  7 1/14 (7.14%)  1
White blood cell decreased †  1/23 (4.35%)  1 0/14 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Muscle weakness lower limb †  1/23 (4.35%)  1 0/14 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Tumor hemorrhage †  1/23 (4.35%)  1 0/14 (0.00%)  0
Nervous system disorders     
Ataxia †  1/23 (4.35%)  1 0/14 (0.00%)  0
Central nervous system necrosis †  0/23 (0.00%)  0 2/14 (14.29%)  2
Dizziness †  1/23 (4.35%)  1 0/14 (0.00%)  0
Hydrocephalus †  1/23 (4.35%)  1 0/14 (0.00%)  0
Muscle weakness left-sided †  1/23 (4.35%)  1 1/14 (7.14%)  1
Seizure †  4/23 (17.39%)  4 2/14 (14.29%)  3
Tremor †  1/23 (4.35%)  1 1/14 (7.14%)  1
entrapped ventricle †  1/23 (4.35%)  1 0/14 (0.00%)  0
Skin and subcutaneous tissue disorders     
Rash maculo-papular †  1/23 (4.35%)  1 0/14 (0.00%)  0
Vascular disorders     
Hypertension †  1/23 (4.35%)  1 0/14 (0.00%)  0
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Stratum 1 Stratum 2
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/23 (17.39%)      4/14 (28.57%)    
Gastrointestinal disorders     
Diarrhea †  1/23 (4.35%)  1 0/14 (0.00%)  0
Nausea †  1/23 (4.35%)  1 0/14 (0.00%)  0
Vomiting †  3/23 (13.04%)  4 0/14 (0.00%)  0
General disorders     
Fatigue †  1/23 (4.35%)  1 1/14 (7.14%)  1
Infections and infestations     
Covid-19 †  0/23 (0.00%)  0 1/14 (7.14%)  1
Injury, poisoning and procedural complications     
Dermatitis radiation †  1/23 (4.35%)  2 0/14 (0.00%)  0
Investigations     
Lymphocyte count decreased †  2/23 (8.70%)  3 0/14 (0.00%)  0
Neutrophil count decreased †  2/23 (8.70%)  2 0/14 (0.00%)  0
White blood cell decreased †  2/23 (8.70%)  2 0/14 (0.00%)  0
Metabolism and nutrition disorders     
Hypocalcemia †  1/23 (4.35%)  1 0/14 (0.00%)  0
Nervous system disorders     
Central nervous system necrosis †  0/23 (0.00%)  0 1/14 (7.14%)  1
Edema cerebral †  1/23 (4.35%)  1 0/14 (0.00%)  0
Headache †  1/23 (4.35%)  1 0/14 (0.00%)  0
Presyncope †  0/23 (0.00%)  0 1/14 (7.14%)  1
Skin and subcutaneous tissue disorders     
Alopecia †  1/23 (4.35%)  2 1/14 (7.14%)  1
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Results Reporting Coordinator
Organization: Children's Oncology Group
Phone: 16264470064
EMail: resultsreportingcoordinator@childrensoncologygroup.org
Layout table for additonal information
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT03581292    
Other Study ID Numbers: NCI-2018-01361
NCI-2018-01361 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
ACNS1721 ( Other Identifier: Children's Oncology Group )
ACNS1721 ( Other Identifier: CTEP )
U10CA180886 ( U.S. NIH Grant/Contract )
First Submitted: July 4, 2018
First Posted: July 10, 2018
Results First Submitted: February 22, 2024
Results First Posted: April 23, 2024
Last Update Posted: May 20, 2024