Study to Evaluate Erlotinib With or Without SNDX-275 (Entinostat) in the Treatment of Patients With Advanced NSCLC

Non-Small-Cell Lung Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00602030
• Other study ID #: SNDX-275-0401
• Status: Completed
• Phase: Phase 1/Phase 2
• 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
• 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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Non-Small Cell Lung
• Carcinoma, Non-Small-Cell Lung
• Non-Small-Cell Lung Carcinoma

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