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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00602030
Other study ID # SNDX-275-0401
Secondary ID
Status Completed
Phase Phase 1/Phase 2
First received
Last updated
Start date January 8, 2008
Est. completion date February 1, 2012

Study information

Verified date August 2022
Source Syndax Pharmaceuticals
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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).


Recruitment information / eligibility

Status Completed
Enrollment 141
Est. completion date February 1, 2012
Est. primary completion date February 4, 2010
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria - Cytologically or histologically confirmed NSCLC of stage IIIb or IV - Received at least 1 but no more than 2 prior chemotherapy or chemoradiotherapy regimens for advanced NSCLC (that did not include erlotinib and valproic acid) and progressed based on radiologic evidence - At least 1 measurable lesion by conventional or spiral computed tomography (CT) scan - Eastern Cooperative Oncology Group (ECOG) performance score of 0, 1, or 2 and life expectancy of at least 6 months - Paraffin-embedded tumor specimen available for correlative studies - Male or female over 18 years of age - Hemoglobin = 9.0 g/dL; platelets = 100 x 10^9/L; absolute neutrophil count (ANC) = 1.5 x 10^9/L without the use of hematopoietic growth factors - Bilirubin and creatinine less than 2 times the upper limit of normal for the institution - Albumin = 2.5 g/dL - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 3 times the upper limit of normal for the institution - Prothrombin time less than 1.5 times the upper limit of normal for the institution - Potassium, magnesium and phosphorus within the normal range for the institution (supplementation is permissible) - Willing to use accepted and effective methods of contraception during the study (both men and women as appropriate) and for 3 months after the last dose of SNDX-275 - Patient or legally acceptable representative has granted written informed consent before any study-specific procedure (including special screening tests) are performed Exclusion Criteria - Prior stem cell transplant - Clinical evidence of central nervous system (CNS) involvement - Prior treatment with an histone deacetylase (HDAC) inhibitor or an epidermal growth factor receptor (EGFR) inhibitor - Currently taking known inhibitors of CYPA4, including but not limited to atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, = 10 mg prednisone, and voriconazole - Currently taking medication(s) on the prohibited medication list - Prior exposure to SNDX-275 - Systemic chemotherapy, radiotherapy, or treatment with an investigational agent without recovery to at least grade 1 or baseline before study drug administration - Daily treatment with = 10 mg prednisone within 28 days before study drug administration - Local or whole brain palliative radiotherapy within 14 days before study drug administration - Currently active second malignancy, or any malignancy within the last 5 years other than cured basal or squamous cell skin carcinoma, cervical carcinoma in situ, carcinoma in situ of the bladder, or papillary thyroid cancer - Inability to swallow oral medications or a gastrointestinal malabsorption condition - Acute infection requiring intravenous (IV) antibiotics, antivirals, or antifungals within 14 days before study drug administration - Known human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection - Another serious or uncontrolled medical condition within 90 days before study drug administration such as acute myocardial infarction, angina, ventricular arrhythmias, hypertension, diabetes mellitus, or renal or hepatic insufficiency - Known hypersensitivity to benzamides - Women who are currently pregnant or breast-feeding - Patient currently is enrolled in (or completed within 28 days before study drug administration) another investigational drug study - Patient has any kind of medical, psychiatric, or behavioral disorder that places the patient at increased risk for study participation or compromises the ability of the patient to give written informed consent and/or to comply with study procedures and requirements

Study Design


Intervention

Drug:
Entinostat
Entinostat tablets on Days 1 and 15 of a 28-day cycle.
Placebo
Placebo-matching entinostat tablets on Days 1 and 15 of a 28-day cycle.
Erlotinib
Erlotinib 150 mg tablets once daily.

Locations

Country Name City State
United States Texas Oncology Amarillo Texas
United States Texas Oncology Austin Texas
United States Texas Oncology Bedford Texas
United States Mahonig Valley Hematology Oncology Associates Boardman Ohio
United States Highline Medical Oncology Burien Washington
United States Hematology Oncology Associates of Illinois Chicago Illinois
United States Texas Oncology Dallas Texas
United States Texas Oncology, Sammons Cancer Center Dallas Texas
United States Rocky Mountain Cancer Center Denver Colorado
United States Oncology Associates of Oregon Eugene Oregon
United States Fairfax Northern Virginia Hematology-Oncology Fairfax Virginia
United States Texas Oncology Fort Worth Texas
United States Texas Oncology Garland Texas
United States Central Indiana Cancer Centers Indianapolis Indiana
United States Dayton Oncology & Hematology Kettering Ohio
United States Texas Oncology Longview Texas
United States Advanced Medical Specialties Miami Florida
United States Texas Oncology Midland Texas
United States Virginia Oncology Associates Norfolk Virginia
United States Ocala Oncology Center Ocala Florida
United States Cancer Centers of Florida Ocoee Florida
United States Texas Oncology Odessa Texas
United States Kansas City Cancer Centers Overland Park Kansas
United States St Joseph Oncology Saint Joseph Missouri
United States The Center for Cancer Care & Research Saint Louis Missouri
United States Cancer Care Northwest Spokane Washington
United States HOPE (Hematology Oncology Physicians & Extenders) Tucson Arizona
United States Texas Oncology Tyler Texas
United States Alliance Hematology Oncology Westminster Maryland
United States Yakima Valley Memorial Hospital/North Star Lodge Yakima Washington

Sponsors (1)

Lead Sponsor Collaborator
Syndax Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Identification of Safe-dose for the Phase 2 Double-blind Phase in the 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. Cycle 1 of Lead-in Phase
Primary 4-Month Progression-free Survival (PFS) Rate in the Double-blind Phase PFS rate at 4 months was defined as the percentage of participants who are progression-free at 4 months. Month 4
Secondary Objective Response Rate (ORR) in the Double-blind Phase 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. Month 6
Secondary 6-Month PFS Rate in the Double-blind Phase PFS rate at 6 months is defined as the percentage of participants who are progression-free at 6 months. Month 6
Secondary Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) by Severity in the Double-blind Phase 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.
First dose of study drug to within 30 days past last dose (Up to 7 months)
Secondary Number of Participants With Grade 3 or 4 Laboratory Variables in the Double-blind Phase 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. Day 1 and 15 of each cycle to safety follow-up 30 days past last dose (up to 7 months)
Secondary 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)
Secondary 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)
Secondary 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)
Secondary 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)
Secondary 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)
Secondary 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)
Secondary 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
Secondary 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
Secondary 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
Secondary 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
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