Study to Evaluate Erlotinib With or Without SNDX-275 (Entinostat) in the Treatment of Patients With Advanced NSCLC
- Conditions
- Carcinoma, Non-Small Cell LungNon-Small-Cell Lung Carcinoma
- Interventions
- Registration Number
- NCT00602030
- Lead Sponsor
- Syndax Pharmaceuticals
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 141
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Lead-in Phase: Erlotinib + Entinostat 10 mg Entinostat 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. Double-blind Phase: Erlotinib + Entinostat 10 mg Erlotinib 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. Lead-in Phase: Erlotinib + Entinostat 5 mg Entinostat 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. Crossover Phase: Erlotinib + Entinostat 10 mg Entinostat 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. Crossover Phase: Erlotinib + Entinostat 10 mg Erlotinib 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. Double-blind Phase: Erlotinib + Placebo 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. Double-blind Phase: Erlotinib + Placebo Erlotinib 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. Lead-in Phase: Erlotinib + Entinostat 5 mg Erlotinib 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. Lead-in Phase: Erlotinib + Entinostat 10 mg Erlotinib 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. Double-blind Phase: Erlotinib + Entinostat 10 mg Entinostat 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.
- Primary Outcome Measures
Name Time Method Identification of Safe-dose for the Phase 2 Double-blind Phase in the Lead-in Phase 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 Month 4 PFS rate at 4 months was defined as the percentage of participants who are progression-free at 4 months.
- Secondary Outcome Measures
Name Time Method 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) An AE is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. Worsening of a pre-existing medical condition was considered an AE if there was either an increase in severity, frequency, or duration of the condition or an association with significantly worse outcomes. A TEAE is an AE that starts after the administration of study drug.
A SAE is any AE that is fatal, life threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth effect or other significant medical hazard.
TEAE severity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 scale where Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, medically significant, Grade 4=Life-threatening and 5=Death.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 ORR was defined as the percentage of participants who had confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) as assessed by the investigator. CR=disappearance of all target lesions; disappearance of non-target lesions and normalization of tumor marker level. PR=At least a 30% decrease in the sum of the longest diameter of target lesions, taking at reference the baseline sum longest diameter.
6-Month PFS Rate in the Double-blind Phase Month 6 PFS rate at 6 months is defined as the percentage of participants who are progression-free at 6 months.
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) Laboratory tests included tests of Hematology and Chemistry. The individual laboratory values were graded by the investigator using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 scale where Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, medically significant, Grade 4=Life-threatening and 5=Death.
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
Trial Locations
- Locations (21)
Fairfax Northern Virginia Hematology-Oncology
🇺🇸Fairfax, Virginia, United States
HOPE (Hematology Oncology Physicians & Extenders)
🇺🇸Tucson, Arizona, United States
Oncology Associates of Oregon
🇺🇸Eugene, Oregon, United States
Ocala Oncology Center
🇺🇸Ocala, Florida, United States
Yakima Valley Memorial Hospital/North Star Lodge
🇺🇸Yakima, Washington, United States
Kansas City Cancer Centers
🇺🇸Overland Park, Kansas, United States
Cancer Centers of Florida
🇺🇸Ocoee, Florida, United States
Advanced Medical Specialties
🇺🇸Miami, Florida, United States
Hematology Oncology Associates of Illinois
🇺🇸Chicago, Illinois, United States
Central Indiana Cancer Centers
🇺🇸Indianapolis, Indiana, United States
St Joseph Oncology
🇺🇸Saint Joseph, Missouri, United States
Dayton Oncology & Hematology
🇺🇸Kettering, Ohio, United States
The Center for Cancer Care & Research
🇺🇸Saint Louis, Missouri, United States
Mahonig Valley Hematology Oncology Associates
🇺🇸Boardman, Ohio, United States
Texas Oncology
🇺🇸Tyler, Texas, United States
Texas Oncology, Sammons Cancer Center
🇺🇸Dallas, Texas, United States
Virginia Oncology Associates
🇺🇸Norfolk, Virginia, United States
Highline Medical Oncology
🇺🇸Burien, Washington, United States
Alliance Hematology Oncology
🇺🇸Westminster, Maryland, United States
Cancer Care Northwest
🇺🇸Spokane, Washington, United States
Rocky Mountain Cancer Center
🇺🇸Denver, Colorado, United States