SNPMiner Trials by Shray Alag


SNPMiner SNPMiner Trials (Home Page)


Report for Clinical Trial NCT01264380

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Phase I, Randomized, Open-label, Multi-center, Two Period Crossover Study to Investigate the Effect of Food on the Pharmacokinetics of a Single Oral Dose of RO5185426, Followed by Administration of 960 mg RO5185426 Twice Daily to BRAF V600E Positive Metastatic Melanoma Patients

This randomized, open-label, two period crossover study will evaluate the effect of food on the pharmacokinetics of a single dose of RO5185426 and the efficacy and safety of continuous administration in patients with BRAF V600E mutation-positive metastatic melanoma. Patients will be randomized to receive in a crossover design single oral doses of RO5185426 with or without food, with a 10-day washout period between doses. Following the crossover periods, patients will receive RO5185426 orally twice daily on a continuous basis until disease progression or unacceptable toxicity occurs.

NCT01264380 Malignant Melanoma
MeSH: Melanoma
HPO: Cutaneous melanoma Melanoma

3 Interventions

Name: RO5185426

Description: Single oral dose, fasted

Type: Drug

1

Name: RO5185426

Description: Single oral dose, with high fat meal

Type: Drug

2

Name: RO5185426

Description: Continuous administration, orally twice daily

Type: Drug

C


Primary Outcomes

Description: Pharmacokinetic (PK) analyses was performed after the completion of Period A and Period B of this study for all participants.

Measure: Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC [0-inf]) in the Fasted and Fed States

Time: Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 hours (h) post-dose (pd) on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd

Description: PK analyses was performed after the completion of Period A and Period B of this study for all participants.

Measure: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Sample With Last Measurable Concentration (AUC[0-last]) in the Fasted and Fed States

Time: Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd

Description: PK analyses was performed after the completion of Period A and Period B of this study for all participants.

Measure: Maximal Observed Plasma Concentration (Cmax) in the Fasted and Fed States

Time: Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd

Description: Single dose Pre-dose concentration is referred as Cmin here. PK analyses was performed after the completion of Period A and Period B of this study for all participants.

Measure: Minimum Observed (Trough) Plasma Concentration (Cmin) in the Fasted and Fed States

Time: Pre-dose on Periods A and B

Description: PK analyses was performed after the completion of Period A and Period B of this study for all participants.

Measure: Time to Reach Maximal Plasma Concentration (Tmax) in the Fasted and Fed States

Time: Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd

Description: T1/2 is the time required for the concentration of the drug to reach half of its original value. PK analyses was performed after the completion of Period A and Period B of this study for all participants.

Measure: Terminal Elimination Half-Life (t1/2) in the Fasted and Fed States

Time: Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd

Description: Apparent first-order terminal elimination rate constant (kel), was calculated as the negative slope of the linear regression of the terminal phase in plasma vemurafenib concentration-time profile using specific appropriate time points. PK analyses was performed after the completion of Period A and Period B of this study for all participants.

Measure: Apparent First-order Terminal Elimination Rate Constant (Kel) in the Fasted and Fed States

Time: Period A: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 1; 24, 36, 48, 72, 96, 144, 192, and 240 h pd and Period B: pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 16 h pd on Day 11; 24, 36, 48, 72, 96, 144, 192, and 240 h pd

Secondary Outcomes

Description: BOR was defined as the best objective response assessed by investigator during the treatment period according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. BOR was the best response recorded from the start of the study treatment until the end of treatment taking into account any requirement for confirmation. It is defined as the number of participants whose best objective response was complete response (CR) or partial response (PR) divided by the total number of efficacy evaluable participants. CR: disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes (whether target or non-target) were non-pathological in size (less than [<] 10 millimeter [mm] short axis). PR: at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Measure: Percentage of Participants With Best Objective Response (BOR) as Complete Response (CR) or Partial Response (PR)

Time: From Baseline then Day 1 of Cycle 3 and 5 (21-day cycle) at Period C thereafter every 2 cycles until Cycle 12 followed by every 4 cycles from Cycle 13 until disease progression or death (Up to Week 124)

Description: OS was defined as the time, in months, from the date of the first study drug to the date of death, regardless of the cause of death.

Measure: Overall Survival (OS)

Time: From Baseline then Day 1 of Cycle 3 and 5 (21-day cycle) at Period C thereafter every 2 cycles until Cycle 12 followed by every 4 cycles from Cycle 13 until death (Up to Week 124)

Purpose: Treatment

Allocation: Randomized

Crossover Assignment


There is one SNP

SNPs


1 V600E

A Phase I, Randomized, Open-label, Multi-center, Two Period Crossover Study to Investigate the Effect of Food on the Pharmacokinetics of a Single Oral Dose of RO5185426, Followed by Administration of 960 mg RO5185426 Twice Daily to BRAF V600E Positive Metastatic Melanoma Patients. --- V600E ---

A Study of the Effect of Food on the Pharmacokinetics of Single Dose RO5185426 And the Safety And Efficacy of Continuous Administration in Patients With BRAF V600E Mutation-Positive Metastatic Melanoma This randomized, open-label, two period crossover study will evaluate the effect of food on the pharmacokinetics of a single dose of RO5185426 and the efficacy and safety of continuous administration in patients with BRAF V600E mutation-positive metastatic melanoma. --- V600E ---

A Study of the Effect of Food on the Pharmacokinetics of Single Dose RO5185426 And the Safety And Efficacy of Continuous Administration in Patients With BRAF V600E Mutation-Positive Metastatic Melanoma This randomized, open-label, two period crossover study will evaluate the effect of food on the pharmacokinetics of a single dose of RO5185426 and the efficacy and safety of continuous administration in patients with BRAF V600E mutation-positive metastatic melanoma. --- V600E --- --- V600E ---

OS was defined as the time, in months, from the date of the first study drug to the date of death, regardless of the cause of death.. Inclusion Criteria: - Adult patients, >/= 18 years of age - Histologically confirmed metastatic melanoma (Stage IV, American Joint Committee on Cancer) - Positive BRAF V600E mutation result determined by Cobas 4800 BRAF V600 Mutation Test - Previously treated patients must have failed at least one prior treatment regimen; if patients have received prior systemic treatments for metastatic melanoma, the time elapsed from previous therapy must be >/= 28 days; patients must have recovered fully from toxicities of all prior therapy - Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 - Evaluable disease (measurable for disease progression according to RECIST criteria) - Adequate hematological, renal and liver function Exclusion Criteria: - Active CNS lesions - History of or known spinal cord compression or carcinomatous meningitis - Anticipated or ongoing administration of anti-cancer therapies other than those administered in this study - Previous malignancy within the past 5 years except for basal or squamous cell carcinoma of the skin, melanoma in-situ and carcinoma in-situ of the cervix - Previous treatment with BRAF inhibitor (sorafenib allowed) or MEK inhibitor - Refractory nausea or vomiting, malabsorption, external biliary shunt, or history of any type of gastrointestinal surgery that would preclude adequate absorption of study drug Inclusion Criteria: - Adult patients, >/= 18 years of age - Histologically confirmed metastatic melanoma (Stage IV, American Joint Committee on Cancer) - Positive BRAF V600E mutation result determined by Cobas 4800 BRAF V600 Mutation Test - Previously treated patients must have failed at least one prior treatment regimen; if patients have received prior systemic treatments for metastatic melanoma, the time elapsed from previous therapy must be >/= 28 days; patients must have recovered fully from toxicities of all prior therapy - Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 - Evaluable disease (measurable for disease progression according to RECIST criteria) - Adequate hematological, renal and liver function Exclusion Criteria: - Active CNS lesions - History of or known spinal cord compression or carcinomatous meningitis - Anticipated or ongoing administration of anti-cancer therapies other than those administered in this study - Previous malignancy within the past 5 years except for basal or squamous cell carcinoma of the skin, melanoma in-situ and carcinoma in-situ of the cervix - Previous treatment with BRAF inhibitor (sorafenib allowed) or MEK inhibitor - Refractory nausea or vomiting, malabsorption, external biliary shunt, or history of any type of gastrointestinal surgery that would preclude adequate absorption of study drug Malignant Melanoma Melanoma null --- V600E ---

OS was defined as the time, in months, from the date of the first study drug to the date of death, regardless of the cause of death.. Inclusion Criteria: - Adult patients, >/= 18 years of age - Histologically confirmed metastatic melanoma (Stage IV, American Joint Committee on Cancer) - Positive BRAF V600E mutation result determined by Cobas 4800 BRAF V600 Mutation Test - Previously treated patients must have failed at least one prior treatment regimen; if patients have received prior systemic treatments for metastatic melanoma, the time elapsed from previous therapy must be >/= 28 days; patients must have recovered fully from toxicities of all prior therapy - Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 - Evaluable disease (measurable for disease progression according to RECIST criteria) - Adequate hematological, renal and liver function Exclusion Criteria: - Active CNS lesions - History of or known spinal cord compression or carcinomatous meningitis - Anticipated or ongoing administration of anti-cancer therapies other than those administered in this study - Previous malignancy within the past 5 years except for basal or squamous cell carcinoma of the skin, melanoma in-situ and carcinoma in-situ of the cervix - Previous treatment with BRAF inhibitor (sorafenib allowed) or MEK inhibitor - Refractory nausea or vomiting, malabsorption, external biliary shunt, or history of any type of gastrointestinal surgery that would preclude adequate absorption of study drug Inclusion Criteria: - Adult patients, >/= 18 years of age - Histologically confirmed metastatic melanoma (Stage IV, American Joint Committee on Cancer) - Positive BRAF V600E mutation result determined by Cobas 4800 BRAF V600 Mutation Test - Previously treated patients must have failed at least one prior treatment regimen; if patients have received prior systemic treatments for metastatic melanoma, the time elapsed from previous therapy must be >/= 28 days; patients must have recovered fully from toxicities of all prior therapy - Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 - Evaluable disease (measurable for disease progression according to RECIST criteria) - Adequate hematological, renal and liver function Exclusion Criteria: - Active CNS lesions - History of or known spinal cord compression or carcinomatous meningitis - Anticipated or ongoing administration of anti-cancer therapies other than those administered in this study - Previous malignancy within the past 5 years except for basal or squamous cell carcinoma of the skin, melanoma in-situ and carcinoma in-situ of the cervix - Previous treatment with BRAF inhibitor (sorafenib allowed) or MEK inhibitor - Refractory nausea or vomiting, malabsorption, external biliary shunt, or history of any type of gastrointestinal surgery that would preclude adequate absorption of study drug Malignant Melanoma Melanoma null --- V600E --- --- 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