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Report for Clinical Trial NCT01586195

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

An Open-Label, Multicenter, Phase II Study Of Continuous Oral Zelboraf (Vemurafenib) in Patients With Locally-Advanced, Unresectable, Stage IIIc Or Metastatic Melanoma and Activating Exon 15 BRAF Mutations Other Than V600E

This is an open-label, multicenter, single-agent, phase II study of continuous oral Zelboraf (vemurafenib) in participants with locally-advanced, unresectable, stage IIIc or metastatic melanoma and activating exon 15 BRAF mutations other than V600E.

NCT01586195 Malignant Melanoma
MeSH: Melanoma
HPO: Cutaneous melanoma Melanoma

1 Interventions

Name: Vemurafenib

Description: Vemurafenib 960 mg BID

Type: Drug

Vemurafenib


Primary Outcomes

Description: BORR was assessed by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. BORR was defined as the number of participants whose best overall response was a complete response (CR) or partial response (PR). CR was defined as complete disappearance of all target lesions and non-target disease. PR was defined as a >/=30% decrease under baseline of the sum of diameters of all target lesions. BORR was summarized along with the associated exact 95% confidence interval (CI) using the method of Clopper-Pearson.

Measure: Best Objective Response Rate (BORR)

Time: Up to 42 months

Secondary Outcomes

Description: In participants with a confirmed CR or PR, time to BORR was defined as the interval between the date of first treatment and the date of first documentation of confirmed CR or PR (whichever occurred first). BORR was assessed by the investigators according to RECIST v1.1. CR was defined as complete disappearance of all target lesions and non-target disease. PR was defined as a >/=30% decrease under baseline of the sum of diameters of all target lesions. Participants without confirmed CR or PR were censored at the date of last tumor assessment. The time to response was summarized using univariate statistics.

Measure: Time to BORR

Time: From start of treatment up to first documentation of confirmed CR or PR (up to 42 months)

Description: In participants with a confirmed CR or PR, duration of response was defined as the time interval between the date of the earliest qualifying response and the date of progressive disease (PD) or death due to any cause. CR was defined as complete disappearance of all target lesions and non-target disease. PR was defined as a >/=30% decrease under baseline of the sum of diameters of all target lesions. PD was defined as a 20% increase in the sum of the longest diameter of target lesions or the appearance of new lesions and increase of at least 5 mm in the sum of diameters of target lesions. Duration of response was summarized using Kaplan-Meier method.

Measure: Duration of Response

Time: From date of earliest qualifying response up to date of disease progression or death (up to 42 months)

Description: PFS was assessed by the investigators according to RECIST v1.1 and defined as the time interval between the date of the first treatment dose and the date of disease progression or death due to any cause, whichever occurred first. PD was defined as a 20% increase in the sum of the longest diameter of target lesions or the appearance of new lesions and increase of at least 5 mm in the sum of diameters of target lesions. PFS was summarized using Kaplan-Meier method.

Measure: Progression-free Survival (PFS)

Time: From start of treatment up to first documentation of disease progression or death (up to 42 months)

Description: OS was defined as the time from the date of first treatment to the date of death due to any cause. OS was summarized using Kaplan-Meier method.

Measure: Overall Survival (OS)

Time: Date of first treatment to date of death due to any cause (up to 42 months)

Measure: Percentage of Participants With 6-Month Survival

Time: Baseline to Month 6

Measure: Percentage of Participants With 12-Month Survival

Time: Baseline to Month 12

Description: An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.

Measure: Number of Participants With an Adverse Event (AE)

Time: Up to 42 months

Purpose: Treatment

Single Group Assignment


There is one SNP

SNPs


1 V600E

An Open-Label, Multicenter, Phase II Study Of Continuous Oral Zelboraf (Vemurafenib) in Patients With Locally-Advanced, Unresectable, Stage IIIc Or Metastatic Melanoma and Activating Exon 15 BRAF Mutations Other Than V600E. --- V600E ---

Study Of Zelboraf (Vemurafenib) in Patients With Locally-Advanced, Unresectable, Stage IIIc Or Metastatic Melanoma and Activating Exon 15 BRAF Mutations Other Than V600E This is an open-label, multicenter, single-agent, phase II study of continuous oral Zelboraf (vemurafenib) in participants with locally-advanced, unresectable, stage IIIc or metastatic melanoma and activating exon 15 BRAF mutations other than V600E. --- V600E ---

Study Of Zelboraf (Vemurafenib) in Patients With Locally-Advanced, Unresectable, Stage IIIc Or Metastatic Melanoma and Activating Exon 15 BRAF Mutations Other Than V600E This is an open-label, multicenter, single-agent, phase II study of continuous oral Zelboraf (vemurafenib) in participants with locally-advanced, unresectable, stage IIIc or metastatic melanoma and activating exon 15 BRAF mutations other than V600E. --- V600E --- --- V600E ---

An AE was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution.. Inclusion Criteria: - Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 - Histologically-confirmed metastatic melanoma (unresectable Stage IIIc or IV) with an activating BRAF mutation other than V600E, as detected by DNA sequencing of exon 15 performed at a centralized laboratory - Measurable disease (as defined by RECIST, v1.1) - Adequate recovery from most recent systemic or local treatment for cancer - Adequate organ function within 28 days prior to initiation of treatment - For women of childbearing potential, agreement to the use of two acceptable methods of contraception, including one barrier method, during the study and for 6 months after discontinuation of vemurafenib - For men with female partners of childbearing potential, agreement to use a latex condom and to advise their female partner to use an additional method of contraception during the study and for 6 months after discontinuation of vemurafenib - Negative serum pregnancy test within 7 days of commencement of treatment in premenopausal women. --- V600E ---

Women who are either surgically sterile or have been post-menopausal for at least 1 year are eligible to participate in this study - Agreement not to donate blood or blood products during the study and for at least 6 months after discontinuation of vemurafenib; for male participants, agreement not to donate sperm during the study and for at least 6 months after discontinuation of vemurafenib - Signed informed consent form (prior to study entry and before performing any study-related procedures) Exclusion Criteria: - Invasive malignancy other than melanoma at the time of enrollment and within 2 years prior to first study drug administration, except for adequately treated (with curative intent) basal or squamous cell carcinoma, in situ carcinoma of the cervix, in situ ductal adenocarcinoma of the breast, in situ prostate cancer, or limited stage bladder cancer or other cancers from which the patient has been disease-free for at least 2 years - Pregnant or breast-feeding - Inability to swallow pills - Concurrent anti-tumor therapy (e.g., chemotherapy, other targeted therapy, radiation therapy, including participation in an experimental drug study) - Radiation therapy 450 ms at baseline - Ongoing cardiac dysrhythmia >/= Grade 2 - Unwillingness to practice effective birth control - Inability to comply with other requirements of the protocol Inclusion Criteria: - Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 - Histologically-confirmed metastatic melanoma (unresectable Stage IIIc or IV) with an activating BRAF mutation other than V600E, as detected by DNA sequencing of exon 15 performed at a centralized laboratory - Measurable disease (as defined by RECIST, v1.1) - Adequate recovery from most recent systemic or local treatment for cancer - Adequate organ function within 28 days prior to initiation of treatment - For women of childbearing potential, agreement to the use of two acceptable methods of contraception, including one barrier method, during the study and for 6 months after discontinuation of vemurafenib - For men with female partners of childbearing potential, agreement to use a latex condom and to advise their female partner to use an additional method of contraception during the study and for 6 months after discontinuation of vemurafenib - Negative serum pregnancy test within 7 days of commencement of treatment in premenopausal women. --- V600E ---



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