A Randomized, Placebo-controlled, Double-blind, Multicenter Phase 2 Study With a Lead in Phase of Erlotinib With or Without SNDX-275 in Patients With NSCLC After Failure In Up to Two Prior Chemotherapeutic Regimens for Advanced Disease
Overview
- Phase
- Phase 1
- Intervention
- Erlotinib
- Conditions
- Non-Small-Cell Lung Carcinoma
- Sponsor
- Syndax Pharmaceuticals
- Enrollment
- 141
- Locations
- 21
- Primary Endpoint
- Identification of Safe-dose for the Phase 2 Double-blind Phase in the Lead-in Phase
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the safety and efficacy of entinostat in combination with erlotinib in the treatment of Advanced Non-Small Cell Lung Cancer (NSCLC).
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Lead-in Phase: Erlotinib + Entinostat 10 mg
Erlotinib 150 mg tablets, orally, daily plus entinostat 10 mg, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Lead-in Phase.
Intervention: Erlotinib
Lead-in Phase: Erlotinib + Entinostat 5 mg
Erlotinib 150 mg, tablets, orally, daily plus entinostat 5 mg, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Lead-in Phase.
Intervention: Entinostat
Lead-in Phase: Erlotinib + Entinostat 5 mg
Erlotinib 150 mg, tablets, orally, daily plus entinostat 5 mg, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Lead-in Phase.
Intervention: Erlotinib
Lead-in Phase: Erlotinib + Entinostat 10 mg
Erlotinib 150 mg tablets, orally, daily plus entinostat 10 mg, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Lead-in Phase.
Intervention: Entinostat
Double-blind Phase: Erlotinib + Entinostat 10 mg
Erlotinib 150 mg, tablets, orally, daily plus entinostat 10 mg, tablets, orally, on Day 1 and 15 of a 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Double-blind Phase.
Intervention: Entinostat
Double-blind Phase: Erlotinib + Entinostat 10 mg
Erlotinib 150 mg, tablets, orally, daily plus entinostat 10 mg, tablets, orally, on Day 1 and 15 of a 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Double-blind Phase.
Intervention: Erlotinib
Double-blind Phase: Erlotinib + Placebo
Erlotinib 150 mg, tablets, orally, daily plus placebo matching entinostat, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Double-blind Phase.
Intervention: Placebo
Double-blind Phase: Erlotinib + Placebo
Erlotinib 150 mg, tablets, orally, daily plus placebo matching entinostat, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities for up to 6 cycles in the Double-blind Phase.
Intervention: Erlotinib
Crossover Phase: Erlotinib + Entinostat 10 mg
Participants in the Double-blind Phase Erlotinib + Placebo arm who experienced disease progression crossed over to receive open-label erlotinib 150 mg, tablets, orally, daily plus entinostat 10 mg, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities.
Intervention: Entinostat
Crossover Phase: Erlotinib + Entinostat 10 mg
Participants in the Double-blind Phase Erlotinib + Placebo arm who experienced disease progression crossed over to receive open-label erlotinib 150 mg, tablets, orally, daily plus entinostat 10 mg, tablets, orally, on Days 1 and 15 of each 28-day cycle until disease progression or intolerable toxicities.
Intervention: Erlotinib
Outcomes
Primary Outcomes
Identification of Safe-dose for the Phase 2 Double-blind Phase in the Lead-in Phase
Time Frame: Cycle 1 of Lead-in Phase
Safe recommended Phase 2 dose was determined based on dose-limiting toxicities (DLT) in Cycle 1. A DLT was defined as any of the following occurring in Cycle 1: Grade 3 or greater nonhematologic toxicity that was considered related to either entinostat or erlotinib or a Grade 4 hematologic toxicity lasting more than 7 days and/or resulting in a dose delay. Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 scale was used where Grade 1=mild, Grade 2=Moderate, Grade 3=Severe, medically significant, Grade 4=life-threatening and 5=death. The dose that was found to be safe is reported.
4-Month Progression-free Survival (PFS) Rate in the Double-blind Phase
Time Frame: Month 4
PFS rate at 4 months was defined as the percentage of participants who are progression-free at 4 months.
Secondary Outcomes
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) by Severity in the Double-blind Phase(First dose of study drug to within 30 days past last dose (Up to 7 months))
- Tmax: Time to Cmax of Entinostat in the Lead-in Phase(Day 1 predose and 0.5, 1, 2, 4 and 6 hours after dose; Days 2 and 8 predose (entinostat alone); Day 15 predose and 0.5, 1, 2, 4, 6 and 24 hours after dose)
- AUC(0-last): Area Under the Concentration-time Curve From Time 0 to Last Quantifiable Concentration in the Lead-in Phase(Day 1 predose and 0.5, 1, 2, 4 and 6 hours after dose; Days 2 and 8 predose (entinostat alone); Day 15 predose and 0.5, 1, 2, 4, 6 and 24 hours after dose)
- Objective Response Rate (ORR) in the Double-blind Phase(Month 6)
- 6-Month PFS Rate in the Double-blind Phase(Month 6)
- Vital Sign Values: Heart Rate in the Double-blind Phase(Day 1 and 15 of each cycle to safety follow-up 30 days past last dose (up to 7 months))
- Vital Sign Values: Respiration Rate in the Double-blind Phase(Day 1 and 15 of each cycle to safety follow-up 30 days past last dose (up to 7 months))
- Vital Sign Values: Weight in the Double-blind Phase(Day 1 and 15 of each cycle to safety follow-up 30 days past last dose (up to 7 months))
- Vital Sign Values: Systolic Blood Pressure in the Double-blind Phase(Day 1 and 15 of each cycle to safety follow-up 30 days past last dose (up to 7 months))
- Vital Sign Values: Diastolic Blood Pressure in the Double-blind Phase(Day 1 and 15 of each cycle to safety follow-up 30 days past last dose (up to 7 months))
- Number of Participants With Grade 3 or 4 Laboratory Variables in the Double-blind Phase(Day 1 and 15 of each cycle to safety follow-up 30 days past last dose (up to 7 months))
- Vital Sign Values: Temperature in the Double-blind Phase(Day 1 and 15 of each cycle to safety follow-up 30 days past last dose (up to 7 months))
- Cmax: Maximum Plasma Concentration of Entinostat in the Lead-in Phase(Day 1 predose and 0.5, 1, 2, 4 and 6 hours after dose; Days 2 and 8 predose (entinostat alone); Day 15 predose and 0.5, 1, 2, 4, 6 and 24 hours after dose)
- AUC(0-24): Area Under the Concentration-time Curve From Time 0 to 24 Hours in the Lead-in Phase(Day 1 predose and 0.5, 1, 2, 4 and 6 hours after dose; Days 2 and 8 predose (entinostat alone); Day 15 predose and 0.5, 1, 2, 4, 6 and 24 hours after dose)