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Report for Clinical Trial NCT01943422

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

Dose-seeking and Efficacy Study of the Combination of the BRAF Inhibitor Vemurafenib and High-dose Interferon Alfa-2b for Therapy of Advanced Melanoma

This is a dose-seeking and efficacy study of combined BRAF Inhibitor Vemurafenib and High-dose Interferon alfa-2b for therapy of advanced melanoma.

NCT01943422 Melanoma
MeSH: Melanoma
HPO: Cutaneous melanoma Melanoma

2 Interventions

Name: High-dose Interferon alfa-2b

Description: •Vemurafenib at standard dosing with a 2 week lead-in period to identify potential effects. IFNα-2b following this (week 2 onwards) at standard induction (4 weeks) and maintenance (48 weeks) doses.

Type: Drug

Vemurafenib + IFNα-2b (10 MU/m2/d) Vemurafenib + IFNα-2b (20 MU/m2/d) Vemurafenib + IFNα-2b(15 MU/m2/d)

Name: Vemurafenib

Description: Vemurafenib is a prescription medicine used to treat melanoma, that has spread to other parts of the body or cannot be removed by surgery, and that has a certain type of abnormal "BRAF" gene.

Type: Drug

Vemurafenib + IFNα-2b (10 MU/m2/d) Vemurafenib + IFNα-2b (20 MU/m2/d) Vemurafenib + IFNα-2b(15 MU/m2/d)


Primary Outcomes

Description: At each dose level, the number of patients experiencing Adverse Events over their course of treatment will be characterized by type of Adverse Event and grade using NCI CTCAE (v4.0), and by time of onset in relation to the first day of therapy.

Measure: Number of Participants with Adverse Events to determine Ph II dose

Time: 12-24 months from study start

Secondary Outcomes

Description: •Progression Free Survival will be evaluated at 6 months using the Kaplan-Meier method. Overall Survival will be measured from the initial date of treatment to the recorded date of death, and analyzed similarly to Progression Free Survival. Overall Survival will also be analyzed with the Kaplan-Meier method. The complete response rate and partial response rate will be estimated by the proportion of patients with a best response respectively by RECIST criteria.

Measure: Progression Free and overall survival (Efficacy)

Time: 48 months

Other Outcomes

Description: Melanoma metastases removed from patients pretreatment, post-BRAFI alone and Post B-RAF+ will be analyzed for expression of IFNAR1 and immunologically relevant molecules such as HLA antigens, APM components and MA; these results will be correlated with T cell infiltration. In addition the metastases will be tested for extent of melanoma cell proliferation and apoptosis.

Measure: Improve tumor STAT signaling

Time: 48 months

Purpose: Treatment

Allocation: Non-Randomized

Single Group Assignment


There are 2 SNPs

SNPs


1 V600E

- BRAF V600E and V600K mutated - Cutaneous squamous cell carcinomas (SCC) lesions identified at baseline must be excised. --- V600E ---


2 V600K

- BRAF V600E and V600K mutated - Cutaneous squamous cell carcinomas (SCC) lesions identified at baseline must be excised. --- V600E --- --- V600K ---



HPO Nodes


HPO:
Cutaneous melanoma
Genes 15
HRAS MITF CDKN2A BRAF NRAS NRAS WRN CDKN2A CXCR4 BAP1 POLH CDK4 ERCC3 XPC MC1R
Melanoma
Genes 98
MGMT NRAS POT1 NRAS XPA CTSC BRCA1 SDHC ERCC4 CXCR4 RAD51C CDKN2B ERCC3 XPC PALLD ERCC2 ERCC2 CHEK2 CDKN2A RAD51D GNAQ SDHD KRAS MBTPS2 BAP1 BAP1 CYSLTR2 RNF43 BAP1 CDKN2A PTPN11 CDK4 BRCA2 ERCC3 MITF TERF2IP ERCC4 CHEK2 BRCA1 TRPV3 POT1 OCA2 TERT CDKN2A AKT1 CDKN2A SF3B1 ERCC6 ERCC5 ERCC5 MDM2 BRCA2 BAP1 GNA11 ACD BRIP1 HRAS MRE11 BRAF TYR TP53 KLLN SEC23B PTEN PIK3CA XPA PERP MITF RAF1 BRAF POLH TP53 BARD1 NRAS SMAD4 RAD50 DDB2 ERCC2 NBN TERT MC1R SLC45A2 WRN PALB2 DDB2 PALB2 CDKN2A SDHB MC1R RAD51 TP53 XPC ERCC3 PTEN CDKN2A POLH CDK4 MC1R