SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT03551626

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

COMBI-APlus: Open-label, Phase IIIb Study of Dabrafenib in COMBInation With Trametinib in the Adjuvant Treatment of Stage III BRAF V600 Mutation-positive Melanoma After Complete Resection to Evaluate the Impact on Pyrexia Related Outcomes of an Adapted Pyrexia AE-management Algorithm (Plus)

This is an open-label Phase IIIb study of dabrafenib in combination with trametinib in the adjuvant treatment of melanoma after complete resection to evaluate the impact on pyrexia related outcomes of an adapted pyrexia AE-management algorithm, as well as safety, efficacy and health-related outcomes. Approximately 600 subjects will be enrolled to receive dabrafenib (150 mg BID) and trametinib (2 mg once daily) combination therapy for 12 months. At enrollment, subjects will be instructed on the pyrexia management algorithm. This study consists of two Periods for Enrolled subjects: - Treatment Period - subjects will receive up to 12 months of treatment. - Follow-up Period - subjects will be followed through 24 months from their first dose date for relapse, and through end of study for overall survival. Follow-up will start once treatment is complete or is prematurely discontinued and continue through the end of the study, regardless of disease recurrence.

NCT03551626 Malignant Melanoma
MeSH: Melanoma Fever
HPO: Cutaneous melanoma Fever Melanoma

2 Interventions

Name: Dabrafenib

Description: Supplied as dabrafenib 50 mg, 75 mg Capsules for oral use

Type: Drug

Dabrafenib and trametinib combination therapy

Name: Trametinib

Description: supplied as trametinib 0.5mg, 2.0mg tablets for oral use

Type: Drug

Dabrafenib and trametinib combination therapy


Primary Outcomes

Description: The composite rate of grade 3/4 pyrexia, ospitalization due to pyrexia, or permanent treatment discontinuation due to pyrexia by 12 months in overall treated subjects

Measure: Change from baseline in composite rate of pyrexia related events

Time: Baseline up to 12 months

Secondary Outcomes

Description: RFS is defined as the time from the date of first dose of the study medication to the date of disease recurrence or death due to any cause.

Measure: Relapse free survival (RFS) from the first dose to disease recurrence or death from any cause

Time: Baseline up to approximately 24 months

Description: OS is defined as the time from date of the first dose of study medication to date of death due to any cause.

Measure: Overall Survival (OS) from the first dose to date of death due to any cause

Time: Baseline up to approximately 24 months

Description: Percentage of patients who experienced pyrexia and required intervention

Measure: Percentage of patients who require management of pyrexia

Time: Baseline up to 12 months

Description: Participants who permanently discontinued treatment due to any Adverse event during treatment

Measure: The percentage of participants who permanently discontinued treatment due to any Adverse event

Time: Baseline up to 12 months

Description: QoL assessed using Function Assessment Cancer Therapy-melanoma (FACT-M) assessment tool. This includes the FACT-Melanoma subscale (FACT-M MS) questionnaire -specific subscale consists of 16 questions for Melanoma Subscale (MS) and 8 questions for Melanoma Surgery Scale (MSS).Each of these questions could have a response of Not at all, a little bit, somewhat, quite a bit and very much. The responses were given a value between 0 and 4 with 4 being best response. The FACT-M Total Score (FACT-M TS) ranges from 0 to 172 and is derived as follows: FACT-M TS= PWB Score + SWB Score + EWB Score + FWB Score + MS Score. Higher scores represent a better quality of life.

Measure: Change From Baseline in Subject-reported Quality of Life Assessed by Functional Assessment Cancer Therapy - Melanoma Total Score (FACT-M MS)

Time: Baseline up to 24 months

Purpose: Treatment

Single Group Assignment


There is one SNP

SNPs


1 V600E

Higher scores represent a better quality of life.. Inclusion Criteria: - Completely resected histologically confirmed cutaneous melanoma stage IIIA (LN metastasis >1 mm), IIIB, IIIC, IIID [AJCC (ed 8)] - V600E/K mutation positive using a validated local test - Subjects presenting with initial resectable lymph node recurrence after a diagnosis of Stage I or II melanoma are eligible. --- V600E ---

Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to study treatment; completely resected basal cell and squamous cell skin cancers and any completely resected carcinoma in situ - History or current evidence of cardiovascular risk - A history or current evidence/risk of retinal vein occlusion (RVO) or central serous retinopathy Inclusion Criteria: - Completely resected histologically confirmed cutaneous melanoma stage IIIA (LN metastasis >1 mm), IIIB, IIIC, IIID [AJCC (ed 8)] - V600E/K mutation positive using a validated local test - Subjects presenting with initial resectable lymph node recurrence after a diagnosis of Stage I or II melanoma are eligible. --- V600E ---



HPO Nodes


HPO:
Cutaneous melanoma
Genes 11
BRAF HRAS XPC CDKN2A POLH ERCC3 BAP1 CXCR4 MC1R NRAS WRN
Fever
Genes 252
CYBB IL10 TET2 MYD88 IL12A IL12B PRSS1 TREX1 IBA57 NLRP12 POU6F2 SLC29A3 ERCC2 GALC ERCC3 ERCC4 ZBTB16 ABL1 ERCC5 PRTN3 DIS3L2 CRLF1 RNF168 HLA-B SPINK1 ACAT1 AVP ERAP1 HLA-DPA1 AVPR2 HLA-DPB1 CYP11B2 TMEM165 HLA-DRB1 SPTA1 CYP21A2 CYBC1 SPTB CFTR NCF1 PSMB4 GATA2 BLNK PSMB8 SCYL1 PSMB9 PEX6 TCIRG1 SRP54 SLCO1B3 UNC13D PTPN22 IKZF1 NCF2 TSC1 NCF4 TSC2 CCND1 GCH1 HMGCL BCL2 TMEM173 BCL6 ADA BCR ADAR TRIP13 ADA2 F5 LYST DDB2 KLRC4 GFI1 MEFV NLRC4 RYR1 STAT3 STAT4 STAT5B NOD2 STIM1 JAK2 LPIN1 IFIH1 MALT1 PTPN3 DST FBP1 GLA STXBP2 GPC3 BRCA2 KLHL7 POMP PTS KCNJ1 PIK3R1 BTK RNASEH2C EIF2B4 MIF EIF2B3 EIF2B2 EIF2B5 SCNN1A SCNN1B NGF SCNN1G FIP1L1 AK2 CCR1 C4A BCL10 ABCC2 NME1 QDPR RAB27A IL23R NOTCH3 ALPL PML COL1A1 PMM2 MPL PMP22 RNASEH2B CACNA1A NPM1 RAG1 RAG2 CACNA1S TCF4 RANBP2 KRT8 TCF3 HTR1A RARA ANK1 WAS WIPF1 MLX SH2B3 KRT18 RB1 RNASEH2A CALR GPR35 NTRK1 SH3KBP1 NUMA1 SLC19A3 IRF8 WT1 ELP1 BIRC3 XIAP SAMHD1 XPA CHD7 XPC ADAMTS13 LBR REST PSTPIP1 NABP1 RUNX1 FAS AQP2 SLCO1B1 TBL1XR1 EDA ATP13A2 NLRP3 POLR3A SLC4A1 CASK IFNGR1 HAVCR2 MST1 RMRP LIFR ORAI1 LIG4 TH LIPA BCAP31 ATP6 SLC11A1 IL36RN SLC12A1 SLC12A3 COX1 COX2 COX3 IGH DCLRE1C LACC1 CD27 TRIM28 IL12A-AS1 EIF2B1 GYPC IGHM BTNL2 ND1 ND2 ND3 ND4 TLR4 ND5 ND6 LPIN2 CHEK2 PRKAR1A LRRC8A ELANE ZFHX2 CD79A CD79B UBAC2 FOXP1 TRNF TRNH CTLA4 TRNK IGLL1 TRNL1 ATM NGLY1 TNFAIP3 TRNQ TNFRSF1A ATP1A2 ATP1A3 TRNS1 TRNS2 TRNV TRNW HBB STX11 IL2RG G6PD IL6 EPB41 GAA H19 PRNP TP53 EPB42 MVK IL7R CYBA
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