SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT02580708

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

A Phase 1/2 Study of the Safety and Efficacy of Rociletinib When Administered in Combination With Trametinib in Patients With Activating EGFR Mutation-positive Advanced or Metastatic Non-small Lung Cancer (NSCLC)

The purpose of this study is to evaluate the safety and anti-tumor effect of rociletinib when administered in combination with trametinib.

NCT02580708 Non-small Cell Lung Cancer
MeSH: Lung Neoplasms Carcinoma, Non-Small-Cell Lung
HPO: Neoplasm of the lung Non-small cell lung carcinoma

2 Interventions

Name: Rociletinib

Type: Drug

Rociletinib and Trametinib

Name: Trametinib

Type: Drug

Rociletinib and Trametinib


Primary Outcomes

Description: Treatment emergent adverse events (AEs), laboratory abnormalities and ECG abnormalities in EGFR-mutant NSCLC patients given oral rociletinib in combination with oral trametinib; defining in Phase 1 the recommended combination dose for further evaluation in Phase 2

Measure: Incidence of treatment-emergent adverse events

Time: Continuously, up to approximately 24 months

Description: ORR according to RECIST Version 1.1 as determined by Investigator assessment

Measure: Objective Response Rate (ORR)

Time: Every 6 weeks until disease progression, up to approximately 24 months

Measure: Cmax of rociletinib and trametinib at steady state

Time: Cycle 2 Day 1 to Day 2

Measure: Tmax of rociletinib and trametinib at steady state

Time: Cycle 2 Day 1 to Day 2

Measure: AUC of rociletinib and trametinib at steady state

Time: Cycle 2 Day 1 to Day 2

Measure: Cmin of rociletinib and trametinib at steady state

Time: Cycle 2 Day 1 to Day 2

Measure: t1/2 of rociletinib at steady state

Time: Cycle 2 Day 1 to Day 2

Secondary Outcomes

Description: DR according to RECIST Version 1.1 as determined by Investigator assessment

Measure: Duration of Response (DR) According to RECIST Version 1.1

Time: Every 6 weeks until disease progression, up to approximately 24 months

Description: DCR according to RECIST Version 1.1 as determined by Investigator assessment

Measure: Disease Control Rate (DCR) According to RECIST Version 1.1

Time: Every 6 weeks until disease progression, up to approximately 24 months

Description: PFS according to RECIST Version 1.1 as determined by Investigator assessment

Measure: Progression Free Survival (PFS) According to RECIST Version 1.1

Time: Every 6 weeks until disease progression, up to approximately 24 months

Measure: Overall Survival (OS)

Time: Every 12 weeks until date of death, up to approximately 60 months

Measure: Longitudinal changes in blood based biomarkers (i.e. mutations in EGFR) in ctDNA

Time: Biomarker samples will be collected from each subject approximately every 3 weeks, up to approximately 24 months

Measure: Cmax of rociletinib metabolites at steady state

Time: Cycle 2 Day 1 to Day 2

Measure: Tmax of rociletinib metabolites at steady state

Time: Cycle 2 Day 1 to Day 2

Measure: AUC of rociletinib metabolites at steady state

Time: Cycle 2 Day 1 to Day 2

Measure: Cmin of rociletinib metabolites at steady state

Time: Cycle 2 Day 1 to Day 2

Purpose: Treatment

Single Group Assignment


There is one SNP

SNPs


1 T790M

Inclusion Criteria: - Written informed consent on an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved ICF before any study-specific evaluation - Histologically or cytologically confirmed metastatic or unresectable locally advanced NSCLC with EGFR activating mutation (excluding exon 20 insertion); measurable disease per RECIST 1.1 - Prior treatment with an EGFR TKI; in Phase 2, prior treatment with a T790M-directed EGFR TKI for patients in Group B. Previous chemotherapy is allowed; in Phase 2, immediate prior therapy must be EGFR TKI - Patient willingness to undergo tumor biopsy at baseline and on treatment (optional for Phase 1; mandatory for Phase 2) - Eastern Cooperative Oncology Group (ECOG) performance status 0-1; life expectancy at least 3 months - Adequate hematological and biological function; LVEF ≥50% Exclusion Criteria: - Documented evidence in tumor of exon 20 insertion, small cell transformation, or MET amplification - Leptomeningeal carcinomatosis or other untreated or symptomatic CNS metastases (asymptomatic CNS metastases allowed if clinically stable without requirement for steroids within 2 weeks) - Known preexisting interstitial lung disease or pneumonitis - Concurrent use of QT-prolonging medication - Uncontrolled diabetes (HA1C > 10%) despite optional therapy - Cardiac abnormalities: - Clinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's method (QTcF) >450 ms - Inability to measure QT interval on ECG - Personal or family history of long QT syndrome - Implantable pacemaker or implantable cardioverter defibrillator - Resting bradycardia < 55 beats/min - Inability to swallow oral study treatment or any gastrointestinal disease or condition that would preclude adequate absorption of study treatment - Presence of serious or unstable concomitant systemic disorder incompatible with the clinical study (eg, substance abuse; uncontrolled intercurrent illness including active infection; arterial thrombosis; unstable respiratory, hepatic, renal or cardiac disease; and other active malignancy) - Pregnant or breastfeeding females and male or female patients who refuse to use adequate contraception during the study and for 16 weeks after the last dose of study treatment - Any contraindication, allergy, or hypersensitivity to rociletinib, trametinib, or excipients Inclusion Criteria: - Written informed consent on an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved ICF before any study-specific evaluation - Histologically or cytologically confirmed metastatic or unresectable locally advanced NSCLC with EGFR activating mutation (excluding exon 20 insertion); measurable disease per RECIST 1.1 - Prior treatment with an EGFR TKI; in Phase 2, prior treatment with a T790M-directed EGFR TKI for patients in Group B. Previous chemotherapy is allowed; in Phase 2, immediate prior therapy must be EGFR TKI - Patient willingness to undergo tumor biopsy at baseline and on treatment (optional for Phase 1; mandatory for Phase 2) - Eastern Cooperative Oncology Group (ECOG) performance status 0-1; life expectancy at least 3 months - Adequate hematological and biological function; LVEF ≥50% Exclusion Criteria: - Documented evidence in tumor of exon 20 insertion, small cell transformation, or MET amplification - Leptomeningeal carcinomatosis or other untreated or symptomatic CNS metastases (asymptomatic CNS metastases allowed if clinically stable without requirement for steroids within 2 weeks) - Known preexisting interstitial lung disease or pneumonitis - Concurrent use of QT-prolonging medication - Uncontrolled diabetes (HA1C > 10%) despite optional therapy - Cardiac abnormalities: - Clinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's method (QTcF) >450 ms - Inability to measure QT interval on ECG - Personal or family history of long QT syndrome - Implantable pacemaker or implantable cardioverter defibrillator - Resting bradycardia < 55 beats/min - Inability to swallow oral study treatment or any gastrointestinal disease or condition that would preclude adequate absorption of study treatment - Presence of serious or unstable concomitant systemic disorder incompatible with the clinical study (eg, substance abuse; uncontrolled intercurrent illness including active infection; arterial thrombosis; unstable respiratory, hepatic, renal or cardiac disease; and other active malignancy) - Pregnant or breastfeeding females and male or female patients who refuse to use adequate contraception during the study and for 16 weeks after the last dose of study treatment - Any contraindication, allergy, or hypersensitivity to rociletinib, trametinib, or excipients Non-small Cell Lung Cancer Lung Neoplasms Carcinoma, Non-Small-Cell Lung This is a Phase 1/2, open-label, non randomized, multicenter study evaluating the safety and efficacy of rociletinib administered in combination with trametinib. --- T790M ---

Inclusion Criteria: - Written informed consent on an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved ICF before any study-specific evaluation - Histologically or cytologically confirmed metastatic or unresectable locally advanced NSCLC with EGFR activating mutation (excluding exon 20 insertion); measurable disease per RECIST 1.1 - Prior treatment with an EGFR TKI; in Phase 2, prior treatment with a T790M-directed EGFR TKI for patients in Group B. Previous chemotherapy is allowed; in Phase 2, immediate prior therapy must be EGFR TKI - Patient willingness to undergo tumor biopsy at baseline and on treatment (optional for Phase 1; mandatory for Phase 2) - Eastern Cooperative Oncology Group (ECOG) performance status 0-1; life expectancy at least 3 months - Adequate hematological and biological function; LVEF ≥50% Exclusion Criteria: - Documented evidence in tumor of exon 20 insertion, small cell transformation, or MET amplification - Leptomeningeal carcinomatosis or other untreated or symptomatic CNS metastases (asymptomatic CNS metastases allowed if clinically stable without requirement for steroids within 2 weeks) - Known preexisting interstitial lung disease or pneumonitis - Concurrent use of QT-prolonging medication - Uncontrolled diabetes (HA1C > 10%) despite optional therapy - Cardiac abnormalities: - Clinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's method (QTcF) >450 ms - Inability to measure QT interval on ECG - Personal or family history of long QT syndrome - Implantable pacemaker or implantable cardioverter defibrillator - Resting bradycardia < 55 beats/min - Inability to swallow oral study treatment or any gastrointestinal disease or condition that would preclude adequate absorption of study treatment - Presence of serious or unstable concomitant systemic disorder incompatible with the clinical study (eg, substance abuse; uncontrolled intercurrent illness including active infection; arterial thrombosis; unstable respiratory, hepatic, renal or cardiac disease; and other active malignancy) - Pregnant or breastfeeding females and male or female patients who refuse to use adequate contraception during the study and for 16 weeks after the last dose of study treatment - Any contraindication, allergy, or hypersensitivity to rociletinib, trametinib, or excipients Inclusion Criteria: - Written informed consent on an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved ICF before any study-specific evaluation - Histologically or cytologically confirmed metastatic or unresectable locally advanced NSCLC with EGFR activating mutation (excluding exon 20 insertion); measurable disease per RECIST 1.1 - Prior treatment with an EGFR TKI; in Phase 2, prior treatment with a T790M-directed EGFR TKI for patients in Group B. Previous chemotherapy is allowed; in Phase 2, immediate prior therapy must be EGFR TKI - Patient willingness to undergo tumor biopsy at baseline and on treatment (optional for Phase 1; mandatory for Phase 2) - Eastern Cooperative Oncology Group (ECOG) performance status 0-1; life expectancy at least 3 months - Adequate hematological and biological function; LVEF ≥50% Exclusion Criteria: - Documented evidence in tumor of exon 20 insertion, small cell transformation, or MET amplification - Leptomeningeal carcinomatosis or other untreated or symptomatic CNS metastases (asymptomatic CNS metastases allowed if clinically stable without requirement for steroids within 2 weeks) - Known preexisting interstitial lung disease or pneumonitis - Concurrent use of QT-prolonging medication - Uncontrolled diabetes (HA1C > 10%) despite optional therapy - Cardiac abnormalities: - Clinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's method (QTcF) >450 ms - Inability to measure QT interval on ECG - Personal or family history of long QT syndrome - Implantable pacemaker or implantable cardioverter defibrillator - Resting bradycardia < 55 beats/min - Inability to swallow oral study treatment or any gastrointestinal disease or condition that would preclude adequate absorption of study treatment - Presence of serious or unstable concomitant systemic disorder incompatible with the clinical study (eg, substance abuse; uncontrolled intercurrent illness including active infection; arterial thrombosis; unstable respiratory, hepatic, renal or cardiac disease; and other active malignancy) - Pregnant or breastfeeding females and male or female patients who refuse to use adequate contraception during the study and for 16 weeks after the last dose of study treatment - Any contraindication, allergy, or hypersensitivity to rociletinib, trametinib, or excipients Non-small Cell Lung Cancer Lung Neoplasms Carcinoma, Non-Small-Cell Lung This is a Phase 1/2, open-label, non randomized, multicenter study evaluating the safety and efficacy of rociletinib administered in combination with trametinib. --- T790M --- --- T790M ---



HPO Nodes


HPO:
Neoplasm of the lung
Genes 43
WT1 KRAS SLC22A18 STK11 IRF1 AKT1 C11ORF95 PRKN PPP2R1B ERBB2 TRPV3 TSC1 POU6F2 TSC2 EWSR1 RELA KEAP1 REST DIS3L2 SFTPA2 GPC3 MBTPS2 LMNA PTEN BRAF BRCA2 EGFR RB1 TRIP13 PDGFRB TERT SFTPC PIK3CA TRIM28 DICER1 MAP3K8 HPGD SLCO2A1 H19 TP53 NOTCH3 BAP1 WRN
Non-small cell lung carcinoma
Genes 2
TP53 BAP1