SNPMiner Trials by Shray Alag


SNPMiner SNPMiner Trials (Home Page)


Report for Clinical Trial NCT01748149

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

Pediatric Neuro-Oncology Consortium (PNOC)-002: Safety, Phase 0, and Pilot Efficacy Study of Vemurafenib, an Oral Inhibitor of BRAFV600E, in Children and Young Adults With Recurrent/Refractory BRAFV600E- or BRAF Ins T Mutant Brain Tumors

This is a multicenter, safety and pharmacokinetic trial to determine the MTD and/or select a recommended phase 2 dose (RP2D) of vemurafenib in children with recurrent or refractory gliomas containing the BRAFV600E or BRAF Ins T mutation.

NCT01748149 Pediatric Recurrent/Refractory BRAFV600E-mutant Gliomas
MeSH: Glioma
HPO: Glioma

1 Interventions

Name: Vemurafenib

Description: Vemurafenib is supplied in 120-mg and 240-mg film-coated tablets packed in bottles for oral administration. Dosing is based on the body surface area (BSA) calculated at the beginning of each course of therapy. The dose prescribed should be rounded to the nearest deliverable dose based on the BSA adjustment and the available pill sizes. Dosing will not exceed the adult MTD of 960 mg twice a day (BID). Patients will be provided with a Medication Diary for vemurafenib, instructed in its use, and asked to bring the diary with them to each appointment. Treatment will be administered on an outpatient basis. Dosing is based on the BSA calculated at the beginning of each course of therapy. The dose prescribed should be rounded to the nearest deliverable dose based on the BSA adjustment and the available pill sizes. Regardless of cohort, patients will self-administer vemurafenib BID at the assigned dose level. Patients will be instructed to hold their dose of vemurafenib for PK or surgery.

Type: Drug

Vemurafenib


Primary Outcomes

Description: To determine if the maximum tolerated dose of vemurafenib established in adults is safe and tolerable in pediatric patients with BRAFV600E-mutant gliomas. (Dose is adjusted for pediatric use. Weighted dose extrapolated from FDA approved standard adult dose)

Measure: Maximum tolerated dose (MTD)/Recommended Phase 2 Dose (RP2D)

Time: Up to 4 weeks

Description: To describe the toxicity profile/dose limiting toxicity (DLT) of vemurafenib in children with recurrent or refractory glioma. DLT will be assessed by monitoring for adverse events, scheduled laboratory assessments, vital sign measurements, ECGs, and physical examinations. The severity of the toxicities will be graded according to the NCI CTCAE v 4.0. Adverse events and clinically significant laboratory abnormalities (meeting Grade 3, 4, or 5 criteria according to CTCAE) will be summarized by maximum intensity and relationship to study drug. Safety will be assessed weekly for the first 4 weeks and then every 4 weeks. Descriptive statistics will be utilized to display the data on toxicity seen. Safety will be assessed weekly for the first 4 weeks and then every 4 weeks. Descriptive statistics will be utilized to display the data on toxicity seen.

Measure: Toxicity Profile (dose limiting toxicities)

Time: Up to 4 weeks

Description: Venous blood samples (2 mL) will be collected in sodium heparin to measure concentrations of vemurafenib for each PK blood collection. To characterize the pharmacokinetics of vemurafenib in pediatric patients. Plasma drug concentrations and pharmacokinetic parameters will be presented in tabular and graphical form. Mandatory plasma pharmacokinetic studies will be performed in all patients enrolled on the MTD, pre-surgical, and "crushed" pill cohorts of this trial. Because the pharmacokinetics of this agent are unknown in the pediatric population, this information will be essential for evaluating toxicity and disease response and for refining dosing in future clinical trials of vemurafenib.

Measure: Concentrations of vemurafenib in the blood found through pharmacokinetic (PK) samples

Time: Up to 4 weeks

Description: To document antitumor activity of treatment with vemurafenib, as measured by objective responses.Objective response will be assessed using the RECIST Response criteria. The response will be collected on case report forms (CRFs). The study team will include complete responses (CR's), partial responses (PR's) and sustained stable disease (SSD- defined as stable disease on two successive scans). The target response rate is 20%. The number and percent of subjects with each type of response will be summarized and presented in data listings.

Measure: Objective Response

Time: Up to 4 weeks

Secondary Outcomes

Description: Subsequent to the safety cohort, the study team will begin enrollment into a presurgical study. Patients who are candidates for surgical resection at the time of relapse, would be eligible for this component of the trial. The aim will be to measure drug levels (based on the dose chosen in the safety cohort) in tumor, with an additional aim to describe target modulation, with vemurafenib treated tumor compared with corresponding archived tissue from prior surgery. Tumor phospho-extracellular signal-regulated kinase (ERK) levels will be used as a molecular readout for agent activity. Drug levels will be measured by liquid chromatography/Mass spec. The statistical analysis will be descriptive and will be limited to frequency tables and summary statistics.

Measure: Intra-tumoral drug concentration Comparison

Time: Up to 4 weeks

Description: Progression-free survival at 6 months (PFS6) is defined as the proportion of patients alive and progression-free 180 days after Study Day 1. Duration of PFS is defined as the time from Study Day 1 to the earlier of disease progression or death due to any cause. All patients included in the study must be assessed for PFS6, even if there are major protocol treatment deviations or if they are ineligible.

Measure: Progression-free survival

Time: Up to 6 months

Other Outcomes

Description: To examine the levels of Phospho-ERK in patient tumor tissue during vemurafenib therapy then compare those to archived tissue on the same patient.

Measure: Levels of Phospho-ERK Comparison

Time: Up to 4 weeks

Purpose: Treatment

Single Group Assignment


There is one SNP

SNPs


1 V600E

Vemurafenib in Children With Recurrent/Refractory BRAF Gene V600E (BRAFV600E)-Mutant Gliomas This is a multicenter, safety and pharmacokinetic trial to determine the MTD and/or select a recommended phase 2 dose (RP2D) of vemurafenib in children with recurrent or refractory gliomas containing the BRAFV600E or BRAF Ins T mutation. --- V600E ---



HPO Nodes


HPO:
Glioma
Genes 50
TSC2 GLI3 BRCA2 TSC1 LRP5 MLH1 PMS2 APC IDH1 MSH6 POT1 TSC2 CDKN2A NF2 MSH3 MSH6 APC NF1 EPCAM TSC1 TGFBR2 SEMA4A IDH1 IDH2 FAN1 APC MSH3 BMPR1A KRAS MLH1 MSH2 C11ORF95 PMS2 MLH3 PIK3CA NBN RELA SETBP1 IFNG RPS20 NF1 PMS1 CHEK2 APC TP53 MSH2 NBN ERBB2 APC NF2