SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT01136967

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

An Open-Label, 2-Cohort, Multicenter, Phase 2 Study of E7080 (Lenvatinib) in Previously Treated Subjects With Unresectable Stage III or Stage IV Melanoma

The purpose of this study is to assess the objective response rate of lenvatinib in previously treated participants with American Joint Committee on Cancer (AJCC) unresectable Stage III or Stage IV melanoma and disease progression.

NCT01136967 Unresectable Stage III Stage IV Melanoma
MeSH: Melanoma
HPO: Cutaneous melanoma Melanoma

1 Interventions

Name: Lenvatinib

Description: Participants received lenvatinib 24 mg orally, once daily continuously in 28-day cycles until disease progression, development of unacceptable toxicity or withdrawal of consent.

Type: Drug

Cohort 1 (V600E BRAF negative) Cohort 2 (V600E BRAF positive)


Primary Outcomes

Description: ORR was defined as the percentage of participants in each cohort who had a best overall response (BOR) of complete response (CR) or partial response (PR) based on Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 for target lesions and assessed by magnetic resonance imaging/computed tomography (MRI/CT) scans, as determined by independent radiologic review (IRR). A BOR of CR required confirmation by a subsequent CR assessment at least 4 weeks later. A BOR of PR required confirmation by a subsequent CR or PR assessment at least 4 weeks later. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to less than 10 millimeters. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. ORR = CR + PR.

Measure: Objective Response Rate (ORR)

Time: From date of first dose of study drug until all participants completed a minimum of 6 cycles (28-day cycles) or discontinued treatment prior to end of Cycle 6 by the date of data cutoff (Jan 2012 and Apr 2013 for Cohort 1 and Cohort 2, respectively)

Secondary Outcomes

Description: PFS was measured as the time from the date of first administration of study treatment until the date of first documentation of disease progression or date of death from any cause (whichever occurred first), as determined by IRR and Investigator based on RECIST v1.1. Disease progression per RECIST v1.1 was defined as at least a 20% relative increase and 5 mm absolute increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions.

Measure: Progression Free Survival (PFS)

Time: From date of first dose of study drug until documentation of disease progression or death from any cause (whichever occurred first) or up to data cutoff (Jan 2012 and Apr 2013 for Cohort 1 and Cohort 2, respectively), up to approximately 2.9 years

Description: OS was defined as the length of time in months from the date of first administration of study drug until the date of death from any cause, and was based on the data cutoff date for each cohort.

Measure: Overall Survival (OS)

Time: From date of first dose of study drug until date of death from any cause or up to data cutoff (Jan 2012 and Apr 2013 for Cohort 1 and Cohort 2, respectively), up to approximately 2.9 years

Description: DCR was defined as the percentage of participants who had a BOR of CR or PR or stable disease (SD). To be assigned a BOR of SD, the time from the first administration of study drug until the date of documented SD needed to be greater than or equal to seven weeks based on IRR and Investigator's assessment. DCR = CR + PR + SD

Measure: Disease Control Rate (DCR)

Time: From date of first dose of study drug until documentation of disease progression or death from any cause (whichever occurred first) or up to data cutoff (Jan 2012 and Apr 2013 for Cohort 1 and Cohort 2, respectively), up to approximately 2.9 years

Description: CBR was defined as the percentage of participants who had a BOR of CR or PR or durable SD (SD lasting greater than or equal to 23 weeks) based on IRR and Investigator's assessment. CBR = CR + PR + durable SD rate

Measure: Clinical Benefit Rate (CBR)

Time: From date of first dose of study drug until documentation of disease progression or death from any cause (whichever occurred first) or up to data cutoff (Jan 2012 and Apr 2013 for Cohort 1 and Cohort 2, respectively), up to approximately 2.9 years

Description: Safety was assessed by monitoring and recording all AEs including all Common Terminology Criteria for Adverse Events (CTCAE) grades and SAEs; regular monitoring of hematology, clinical chemistry, and urine values; physical examinations; and regular measurement of vital signs, electrocardiograms (ECGs), and multi-gated acquisition (MUGA) scans or echocardiogram.

Measure: Number of Participants With Adverse Events (AEs)/ Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Lenvatinib

Time: For each participant, from the first patient first dose till 30 days after the last dose of study drug, up to approximately 2.9 years

Description: Due to the sparse PK sampling in this study, the data were pooled with data from other Phase 1 studies conducted in participants with solid tumors.

Measure: Pharmacokinetics and Pharmacodynamics

Time: Predose and 2 to 12 hours postdose at Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1

Purpose: Treatment

Allocation: Non-Randomized

Parallel Assignment


There is one SNP

SNPs


1 V600E

More than 2 prior systemic anticancer regimen treatments including immunotherapies for unresectable Stage III or Stage IV disease (if BRAF V600E mutation negative) or not previously treated with BRAF V600E-targeted therapy or received in the past more than 2 prior systemic anticancer regimen treatments, including immunotherapies, in addition to a BRAF-V600E-targeted therapy (if BRAF V600E mutation positive). --- V600E ---

More than 2 prior systemic anticancer regimen treatments including immunotherapies for unresectable Stage III or Stage IV disease (if BRAF V600E mutation negative) or not previously treated with BRAF V600E-targeted therapy or received in the past more than 2 prior systemic anticancer regimen treatments, including immunotherapies, in addition to a BRAF-V600E-targeted therapy (if BRAF V600E mutation positive). --- V600E --- --- V600E ---

More than 2 prior systemic anticancer regimen treatments including immunotherapies for unresectable Stage III or Stage IV disease (if BRAF V600E mutation negative) or not previously treated with BRAF V600E-targeted therapy or received in the past more than 2 prior systemic anticancer regimen treatments, including immunotherapies, in addition to a BRAF-V600E-targeted therapy (if BRAF V600E mutation positive). --- V600E --- --- V600E --- --- V600E ---

More than 2 prior systemic anticancer regimen treatments including immunotherapies for unresectable Stage III or Stage IV disease (if BRAF V600E mutation negative) or not previously treated with BRAF V600E-targeted therapy or received in the past more than 2 prior systemic anticancer regimen treatments, including immunotherapies, in addition to a BRAF-V600E-targeted therapy (if BRAF V600E mutation positive). --- V600E --- --- V600E --- --- V600E --- --- V600E ---

Cohort 1 enrolled participants not harboring the V600E BRAF mutation with disease progression following up to 2 prior systemic anticancer regimens (excluding anti-VEGF) for unresectable Stage III or Stage IV melanoma, and is referred to as Cohort 1 or V600E BRAF negative. --- V600E ---

Cohort 1 enrolled participants not harboring the V600E BRAF mutation with disease progression following up to 2 prior systemic anticancer regimens (excluding anti-VEGF) for unresectable Stage III or Stage IV melanoma, and is referred to as Cohort 1 or V600E BRAF negative. --- V600E --- --- V600E ---

Cohort 2 enrolled participants harboring the activating BRAF mutations (mainly the V600E mutation) with disease progression following BRAF V600E-targeted therapy, and is referred to as Cohort 2 or V600E BRAF positive. --- V600E ---

Cohort 2 enrolled participants harboring the activating BRAF mutations (mainly the V600E mutation) with disease progression following BRAF V600E-targeted therapy, and is referred to as Cohort 2 or V600E BRAF positive. --- V600E --- --- V600E ---

Cohort 2 enrolled participants harboring the activating BRAF mutations (mainly the V600E mutation) with disease progression following BRAF V600E-targeted therapy, and is referred to as Cohort 2 or V600E BRAF positive. --- V600E --- --- V600E --- --- V600E ---



HPO Nodes


HPO:
Cutaneous melanoma
Genes 11
BRAF HRAS XPC CDKN2A POLH ERCC3 BAP1 CXCR4 MC1R NRAS WRN
Melanoma
Genes 64
RAD51 RAD51C TYR RAD51D CDKN2A KRAS CDKN2B RAF1 CDKN2D MRE11 CYSLTR2 ERCC2 KLLN PTPN11 ERCC3 BRIP1 ERCC4 ERCC5 ERCC6 SF3B1 NRAS MGMT BRCA1 MBTPS2 BRAF ACD BRCA2 PIK3CA CXCR4 CTSC POLH POT1 MC1R MITF WRN CHEK2 HRAS BARD1 NBN AKT1 SLC45A2 GNA11 TRPV3 XPA OCA2 XPC GNAQ PTEN MDM2 TERT DDB2 RNF43 PALLD PALB2 TERF2IP SEC23B TP53 SDHB SDHC SDHD SMAD4 BAP1 CDK4 RAD50