SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT03581292

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

A Phase 2 Study of Veliparib (ABT-888) and Local Irradiation, Followed by Maintenance Veliparib and Temozolomide, in Patients With Newly Diagnosed High-Grade Glioma (HGG) Without H3 K27M or BRAFV600 Mutations

This phase II trial studies how well veliparib, radiation therapy, and temozolomide work in treating patients with newly diagnosed malignant glioma without H3 K27M or BRAFV600 mutations. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving veliparib, radiation therapy, and temozolomide may work better in treating patients with newly diagnosed malignant glioma without H3 K27M or BRAFV600 mutations compared to radiation therapy and temozolomide alone.

NCT03581292 Anaplastic Astrocytoma BRAF V600 Wild Type Glioblastoma H3 K27M Negative Malignant Glioma
MeSH: Glioblastoma Glioma Astrocytoma
HPO: Astrocytoma Glioblastoma multiforme Glioma Subependymal giant-cell astrocytoma

3 Interventions

Name: Radiation Therapy

Description: Undergo radiation therapy

Type: Radiation

Treatment (veliparib, radiation therapy, temozolomide)

Name: Temozolomide

Description: Given PO

Type: Drug

Treatment (veliparib, radiation therapy, temozolomide)

Name: Veliparib

Description: Given PO

Type: Drug

Treatment (veliparib, radiation therapy, temozolomide)


Primary Outcomes

Description: Analysis will be based on a 2-sample, 1 sided logrank test. For each stratum will also consider Cox models that incorporate known prognostic factors as feasible including resection status (gross total resection [GTR] versus [vs.] < GTR) and tumor grade (grade 3 vs. 4), spinal primaries vs. others, etc. to ensure that these variables do not have undue influence on the overall outcome. For patients with measurable disease at baseline, will also report the objective response rate.

Measure: Event free survival (EFS)

Time: Up to 5.5 years

Secondary Outcomes

Measure: Objective response

Time: Up to 5.5 years

Measure: Overall survival (OS)

Time: Up to 5.5 years

Other Outcomes

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.

Measure: Biomarker analysis

Time: Up to 5.5 years

Purpose: Treatment

Single Group Assignment


There is one SNP

SNPs


1 K27M

A Phase 2 Study of Veliparib (ABT-888) and Local Irradiation, Followed by Maintenance Veliparib and Temozolomide, in Patients With Newly Diagnosed High-Grade Glioma (HGG) Without H3 K27M or BRAFV600 Mutations. --- K27M ---

Veliparib, Radiation Therapy, and Temozolomide in Treating Patients With Newly Diagnosed Malignant Glioma Without H3 K27M or BRAFV600 Mutations This phase II trial studies how well veliparib, radiation therapy, and temozolomide work in treating patients with newly diagnosed malignant glioma without H3 K27M or BRAFV600 mutations. --- K27M ---

Veliparib, Radiation Therapy, and Temozolomide in Treating Patients With Newly Diagnosed Malignant Glioma Without H3 K27M or BRAFV600 Mutations This phase II trial studies how well veliparib, radiation therapy, and temozolomide work in treating patients with newly diagnosed malignant glioma without H3 K27M or BRAFV600 mutations. --- K27M --- --- K27M ---

Giving veliparib, radiation therapy, and temozolomide may work better in treating patients with newly diagnosed malignant glioma without H3 K27M or BRAFV600 mutations compared to radiation therapy and temozolomide alone. --- K27M ---

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.. Inclusion Criteria: - Stratum 1 (IDH wild-type): Patients must be >= 3 years of age and =< 21 years of age at the time of enrollment - Stratum 2 (IDH mutant): Patients must be >= 3 years of age and =< 25 years of age at the time of enrollment - Patients must have eligibility confirmed by rapid central pathology and central molecular screening reviews performed on APEC14B1: - Newly-diagnosed high-grade glioma such as anaplastic astrocytoma or glioblastoma - Negative results for H3 K27M by immunohistochemistry (IHC) - Negative results for BRAFV600 mutation by next-generation sequencing (NGS) - Patients must have histological verification of diagnosis. --- K27M ---

If lumbar CSF cytology is positive, the patient is considered to have M+ disease and is ineligible - Note: False positive cytology can occur within 10 days of surgery - Patients with gliomatosis cerebri type 1 or 2 - Patients who are not able to receive protocol specified radiation therapy - Patients must not be currently receiving other anti-cancer agents - Patients with known constitutional mismatch repair deficiency syndrome (CMMR-D)/biallelic mismatch repair deficiency (bMMRD) - Female patients who are pregnant are ineligible due to risks of fetal and teratogenic adverse events as seen in animal/human studies - Lactating females are not eligible unless they have agreed not to breastfeed their infants - Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained - Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation and for 6 months after the last dose of protocol-specified chemotherapy Inclusion Criteria: - Stratum 1 (IDH wild-type): Patients must be >= 3 years of age and =< 21 years of age at the time of enrollment - Stratum 2 (IDH mutant): Patients must be >= 3 years of age and =< 25 years of age at the time of enrollment - Patients must have eligibility confirmed by rapid central pathology and central molecular screening reviews performed on APEC14B1: - Newly-diagnosed high-grade glioma such as anaplastic astrocytoma or glioblastoma - Negative results for H3 K27M by immunohistochemistry (IHC) - Negative results for BRAFV600 mutation by next-generation sequencing (NGS) - Patients must have histological verification of diagnosis. --- K27M ---

If lumbar CSF cytology is positive, the patient is considered to have M+ disease and is ineligible - Note: False positive cytology can occur within 10 days of surgery - Patients with gliomatosis cerebri type 1 or 2 - Patients who are not able to receive protocol specified radiation therapy - Patients must not be currently receiving other anti-cancer agents - Patients with known constitutional mismatch repair deficiency syndrome (CMMR-D)/biallelic mismatch repair deficiency (bMMRD) - Female patients who are pregnant are ineligible due to risks of fetal and teratogenic adverse events as seen in animal/human studies - Lactating females are not eligible unless they have agreed not to breastfeed their infants - Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained - Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation and for 6 months after the last dose of protocol-specified chemotherapy Anaplastic Astrocytoma BRAF V600 Wild Type Glioblastoma H3 K27M Negative Malignant Glioma Glioblastoma Glioma Astrocytoma PRIMARY OBJECTIVES: I. To determine whether veliparib (ABT-888), when added to radiotherapy (RT) and temozolomide, is efficacious for the treatment of patients with newly-diagnosed high-grade glioma (HGG) whose tumors' molecular profile are wild-type for H3 K27M, BRAF, and IDH1/2. --- K27M ---

If lumbar CSF cytology is positive, the patient is considered to have M+ disease and is ineligible - Note: False positive cytology can occur within 10 days of surgery - Patients with gliomatosis cerebri type 1 or 2 - Patients who are not able to receive protocol specified radiation therapy - Patients must not be currently receiving other anti-cancer agents - Patients with known constitutional mismatch repair deficiency syndrome (CMMR-D)/biallelic mismatch repair deficiency (bMMRD) - Female patients who are pregnant are ineligible due to risks of fetal and teratogenic adverse events as seen in animal/human studies - Lactating females are not eligible unless they have agreed not to breastfeed their infants - Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained - Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation and for 6 months after the last dose of protocol-specified chemotherapy Anaplastic Astrocytoma BRAF V600 Wild Type Glioblastoma H3 K27M Negative Malignant Glioma Glioblastoma Glioma Astrocytoma PRIMARY OBJECTIVES: I. To determine whether veliparib (ABT-888), when added to radiotherapy (RT) and temozolomide, is efficacious for the treatment of patients with newly-diagnosed high-grade glioma (HGG) whose tumors' molecular profile are wild-type for H3 K27M, BRAF, and IDH1/2. --- K27M --- --- K27M ---

To determine whether veliparib (ABT-888), when added to RT and temozolomide, is efficacious for the treatment of patients with newly-diagnosed HGG whose tumors' molecular profile are wild-type for H3 K27M and BRAF and harbor an IDH1/2 mutation. --- K27M ---



HPO Nodes


HPO:
Astrocytoma
Genes 14
NF2 APC MLH1 CDKN2A MSH6 ERBB2 TSC1 TSC2 PMS2 MSH2 MSH3 IDH1 IDH2 NF1
Glioblastoma multiforme
Genes 16
PMS1 APC MLH1 KRAS EPCAM TGFBR2 PIK3CA MSH6 ERBB2 RPS20 BMPR1A PMS2 MSH2 MLH3 SEMA4A FAN1
Glioma
Genes 30
CHEK2 PMS1 APC MLH1 CDKN2A KRAS TGFBR2 LRP5 NBN MSH6 C11ORF95 ERBB2 RPS20 TSC1 BMPR1A TSC2 RELA PMS2 MSH2 MSH3 MLH3 IDH1 IDH2 SEMA4A NF1 NF2 EPCAM PIK3CA SETBP1 FAN1
Subependymal giant-cell astrocytoma
Genes 2
TSC1 TSC2