SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT01336634

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

A Phase II Study of the BRAF Inhibitor Dabrafenib as a Single Agent and in Combination With the MEK Inhibitor Trametinib in Subjects With BRAF V600E Mutation Positive Metastatic (Stage IV) Non-small Cell Lung Cancer

Dabrafenib is a potent and selective inhibitor of BRAF kinase activity. This is a Phase II, non-randomized, open-label study to assess the efficacy, safety, and tolerability of dabrafenib administered as a single agent and in combination with trametinib in stage IV disease to subjects with BRAF mutant advanced non-small cell lung cancer. Subjects will receive dabrafenib 150 mg twice daily (BID) in monotherapy treatment and dabrafenib 150 mg bid and trametinib 2 mg once daily in combination therapy and continue on treatment until disease progression, death, or unacceptable adverse event.

NCT01336634 Cancer
MeSH: Lung Neoplasms Carcinoma, Non-Small-Cell Lung
HPO: Neoplasm of the lung Non-small cell lung carcinoma

2 Interventions

Name: Dabrafenib

Description: Dabrafenib study treatment will be provided by GSK as 50 mg and 75 mg hydroxypropyl methylcellulose (HPMC) capsules. Each capsule contains 50 mg or 75 mg of free base (present as the mesylate salt).

Type: Drug

Cohort A Cohort C Cohort B

Name: Trametinib

Description: Trametinib study treatment will be provided as 0.5 mg and 2 mg tablets. Each tablet will contain 0.5 mg or 2 mg of trametinib parent (present as the DMSO solvate)

Type: Device

Cohort C Cohort B


Primary Outcomes

Description: ORR is defined as the percentage of par. with a confirmed complete response (CR) or partial response (PR) by investigator assessment as per Response Evaluation Criteria In Solid Tumors evaluates the response on the basis of target and non-target lesions, and best over all response. The response rate was analyzed every 6 weeks (wks) after initiation of study treatment until Week 36 and then every 12 wks until discharge or crossover. Percentage of par. analyzed as number of par. having overall response on the date of analysis from Baseline multiply by 100. The Second Line Plus All Treated Population used for cohort A and B consisted of all par. in the All Treated Population who had received at least one line of prior anti-cancer therapy for advanced/metastatic disease. The First-Line All Treated Population used for cohort C consisted of all par. in the All Treated Population who had not received any prior anti-cancer therapy for advanced/metastatic disease.

Measure: Percentage of Participants With Overall Response Rate (ORR) at the Date of Analysis

Time: At Week 6 then every 6 weeks up to Week 36.and then every 12 weeks until discharge, for an average of 13.8 months

Secondary Outcomes

Description: DoR is defined for the subset of participants with confirmed CR or PR, as the time from first documented evidence of CR or PR until time of first documented disease progression or death due to any cause. The response was analyzed every 6 weeks after initiation of study treatment until Week 36 and then every 12 wks. Disease progression will be based on radiological assessments [magnetic resonance imaging (MRI) or computed tomography (CT)]. Confidence Intervals (CIs) estimated using the Brookmeyer Crowley method. Upper limit of confidence interval was not reached as data were not yet mature. A value of NA indicates where no data is available or not able to determine the value for Arm 3 due to a low event rate in that population (27 percent).

Measure: Duration of Response (DoR) at the Date of Analysis

Time: At Week 6 then every 6 weeks up to Week 36.and then every 12 weeks until discharge, for an average of 13.8 months

Description: PFS is defined as the interval between first dose and the earliest date of disease progression or death due to any cause. The target and non-target lesions were identified at time of screening and the same lesions were re-assessed by a contrast-enhanced brain magnetic resonance imaging (MRI) or Computed tomography (CT) every 6 wks after initiation of study treatment until Week 36 and then every 12 wks. CI estimated using the Brookmeyer Crowley method. A value of NA indicates where no data is available or not able to determine the value for Arm 3 due to a low event rate in the population (36 percent).

Measure: Progression Free Survival (PFS) at the Date of Analysis

Time: At Week 6 then every 6 weeks up to Week 36.and then every 12 weeks until discharge, for an average of 13.8 months

Description: OS defined as the time from first dose until death due to any cause. CI estimated using the Brookmeyer Crowley method. A value of NA indicates where no data is available or not able to determine the value. The upper bound of the 95 percent CI for the median was not reached due to insufficient event rates for Arm 2 (58 percent) and Arm 3 (28 percent).

Measure: Overall Survival (OS) at the Date of Analysis

Time: At Week 6 then every 6 weeks up to Week 36.and then every 12 weeks until discharge, for an average of 13.8 months

Description: Number of participants with abnormal values of vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR) and temperature were evaluated. Participants with worst case post-Baseline vital sign values were presented at the given timepoints. Only those participants with data available at the specified data points were analyzed. All treated population was used for monotherapy cohort which comprised of all participants in the monotherapy cohort who receive at least one dose of study treatment. HR: <60 bpm clinical concern-low; >100 bpm Clinical concern-high Temperature: <=35 °C clinical concern - low; >=38 °C clinical concern - high For SBP change from baseline, the following categories will be used: Grade 0: <120 mm Hg; Grade 1: >=120-<140 mmHg; Grade 2: >=140-<160 mmHg; Grade 3: >=160 mmHg; For DBP change from baseline, the following categories will be used: Grade 0: <80 mm Hg; Grade 1: >=80-<90 mmHg; Grade 2: 90-<100 mmHg; Grade 3: >=100mmHg

Measure: Number of Participants With Abnormal Vital Signs Values

Time: Up to Week 12 and then every 3 weeks until discharge, for an average of 13.8 months

Description: Single measurements of 12-lead ECGs were obtained at given time points using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT and corrected QT (QTc) interval. ECG values at worst case post-Baseline were categorized as 'clinically significant change from Baseline' and 'not a clinically significant change'.

Measure: Number of Participants With Abnormal Electrocardiogram (ECG) Values

Time: Week 3, Week 6, Week 15 and then every 9 weeks until discharge, for an average of 13.8 months

Description: Echocardiography scans were obtained at given time points using an echocardiogram and the findings for left ventricular ejection fraction (LVEF) were obtained. LVEF values at worst case post-Baseline were recorded as any increase and any decrease values.

Measure: Number of Participants With Abnormal Echocardiogram Findings

Time: Week 6, Week 15 and then every 9 weeks until discharge, for an average of 13.8 months

Description: Blood samples were collected from participants for evaluation of clinical chemistry parameters by worst case post-Baseline increase. The clinical chemistry parameters included creatinine, phosphate and high and low calcium, glucose, magnesium, potassium and sodium. Participants were counted in the category that their values shows any grade increase , Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Measure: Number of Participants With Abnormal Clinical Chemistry Values

Time: Up to Week 12 and then every 3 weeks until discharge, for an average of 13.8 months

Description: Blood samples were collected from participants for evaluation of hematology parameters by worst case post-Baseline increase. The hematology parameters included leukocytes, neutrophils, platelets and high and low hemoglobin and lymphocytes. Participants were counted in the category that their values shows any grade increase , Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).

Measure: Number of Participants With Abnormal Hematology Values

Time: Up to Week 12 and then every 3 weeks until discharge, for an average of 13.8 months

Description: An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth effect, other situations and is associated with liver injury or impaired liver function.

Measure: Number of Participants With AEs and Serious AEs (SAEs)

Time: Up to Week 12 and then every 3 weeks up to follow up, for an average of 13.8 months

Description: Blood samples from participants were collected for population pharmacokinetic analysis including CL/F following oral dosing of dabrafenib and trametinib.

Measure: Apparent Clearance (CL/F) of Dabrafenib and Trametinib

Time: Week 3, Week 6, Week 12 and Week 18

Description: Blood samples from participants were collected for population pharmacokinetic analysis including V/F following oral dosing of dabrafenib and trametinib.

Measure: Volume of Distribution (V/F) of Dabrafenib and Trametinib

Time: Week 3, Week 6, Week 12 and Week 18

Purpose: Treatment

Allocation: Non-Randomized

Single Group Assignment


There is one SNP

SNPs


1 V600E

A Phase II Study of the BRAF Inhibitor Dabrafenib as a Single Agent and in Combination With the MEK Inhibitor Trametinib in Subjects With BRAF V600E Mutation Positive Metastatic (Stage IV) Non-small Cell Lung Cancer. --- V600E ---

Study of Selective BRAF Kinase Inhibitor Dabrafenib Monotherapy Twice Daily and in Combination With Dabrafenib Twice Daily and Trametinib Once Daily in Combination Therapy in Subjects With BRAF V600E Mutation Positive Metastatic (Stage IV) Non-small Cell Lung Cancer. --- V600E ---

Subjects in Cohort C will be required to have not received prior systemic anti-cancer therapies for metastatic disease (i.e., dabrafenib/trametinib will be 1st line treatment for metastatic disease); - Measurable disease according to Response Evaluation Criteria in Solid Tumors [RECIST 1.1]; - At least 18 years of age; - Anticipated life expectancy of at least three months; - Presence of a BRAF V600E mutation in lung cancer tissue. --- V600E ---



HPO Nodes


HPO:
Neoplasm of the lung
Genes 43
WT1 KRAS SLC22A18 STK11 IRF1 AKT1 C11ORF95 PRKN PPP2R1B ERBB2 TRPV3 TSC1 POU6F2 TSC2 EWSR1 RELA KEAP1 REST DIS3L2 SFTPA2 GPC3 MBTPS2 LMNA PTEN BRAF BRCA2 EGFR RB1 TRIP13 PDGFRB TERT SFTPC PIK3CA TRIM28 DICER1 MAP3K8 HPGD SLCO2A1 H19 TP53 NOTCH3 BAP1 WRN
Non-small cell lung carcinoma
Genes 2
TP53 BAP1