Clinical trial NCT00602030: Study to Evaluate Erlotinib With or Without SNDX-275 (Entinostat) in the Treatment of Patients With Advanced NSCLC
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Non-Small-Cell Lung Carcinoma
Carcinoma, Non-Small Cell Lung
Keywords: lung cancer
NSCLC
lung neoplasms
respiratory
Lead sponsor: Syndax Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2008-01-28
Enrollment: 141
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Identification of Safe-dose for the Phase 2 Double-blind Phase in the Lead-in Phase
timeFrame: Cycle 1 of Lead-in Phase
measure: 4-Month Progression-free Survival (PFS) Rate in the Double-blind Phase
timeFrame: Month 4
Secondary outcomes:
measure: Objective Response Rate (ORR) in the Double-blind Phase
timeFrame: Month 6
measure: 6-Month PFS Rate in the Double-blind Phase
timeFrame: Month 6
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) by Severity in the Double-blind Phase
timeFrame: First dose of study drug to within 30 days past last dose (Up to 7 months)
measure: Number of Participants With Grade 3 or 4 Laboratory Variables in the Double-blind Phase
timeFrame: Day 1 and 15 of each cycle to safety follow-up 30 days past last dose (up to 7 months)
measure: Vital Sign Values: Systolic Blood Pressure in the Double-blind Phase
timeFrame: Day 1 and 15 of each cycle to safety follow-up 30 days past last dose (up to 7 months)
measure: Vital Sign Values: Diastolic Blood Pressure in the Double-blind Phase
timeFrame: Day 1 and 15 of each cycle to safety follow-up 30 days past last dose (up to 7 months)
measure: Vital Sign Values: Heart Rate in the Double-blind Phase
timeFrame: Day 1 and 15 of each cycle to safety follow-up 30 days past last dose (up to 7 months)
measure: Vital Sign Values: Respiration Rate in the Double-blind Phase
timeFrame: Day 1 and 15 of each cycle to safety follow-up 30 days past last dose (up to 7 months)
measure: Vital Sign Values: Temperature in the Double-blind Phase
timeFrame: Day 1 and 15 of each cycle to safety follow-up 30 days past last dose (up to 7 months)
measure: Vital Sign Values: Weight in the Double-blind Phase
timeFrame: Day 1 and 15 of each cycle to safety follow-up 30 days past last dose (up to 7 months)
measure: Cmax: Maximum Plasma Concentration of Entinostat in the Lead-in Phase
timeFrame: 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
measure: Tmax: Time to Cmax of Entinostat in the Lead-in Phase
timeFrame: 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
measure: AUC(0-24): Area Under the Concentration-time Curve From Time 0 to 24 Hours in the Lead-in Phase
timeFrame: 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
measure: AUC(0-last): Area Under the Concentration-time Curve From Time 0 to Last Quantifiable Concentration in the Lead-in Phase
timeFrame: 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
Other outcomes:
Locations:
city: Tucson
country: United States
facility: HOPE (Hematology Oncology Physicians & Extenders)
state: Arizona
city: Denver
country: United States
facility: Rocky Mountain Cancer Center
state: Colorado
city: Miami
country: United States
facility: Advanced Medical Specialties
state: Florida
city: Ocala
country: United States
facility: Ocala Oncology Center
state: Florida
city: Ocoee
country: United States
facility: Cancer Centers of Florida
state: Florida
city: Chicago
country: United States
facility: Hematology Oncology Associates of Illinois
state: Illinois
city: Indianapolis
country: United States
facility: Central Indiana Cancer Centers
state: Indiana
city: Overland Park
country: United States
facility: Kansas City Cancer Centers
state: Kansas
city: Westminster
country: United States
facility: Alliance Hematology Oncology
state: Maryland
city: Saint Joseph
country: United States
facility: St Joseph Oncology
state: Missouri
city: Saint Louis
country: United States
facility: The Center for Cancer Care & Research
state: Missouri
city: Boardman
country: United States
facility: Mahonig Valley Hematology Oncology Associates
state: Ohio
city: Kettering
country: United States
facility: Dayton Oncology & Hematology
state: Ohio
city: Eugene
country: United States
facility: Oncology Associates of Oregon
state: Oregon
city: Amarillo
country: United States
facility: Texas Oncology
state: Texas
city: Austin
country: United States
facility: Texas Oncology
state: Texas
city: Bedford
country: United States
facility: Texas Oncology
state: Texas
city: Dallas
country: United States
facility: Texas Oncology, Sammons Cancer Center
state: Texas
city: Dallas
country: United States
facility: Texas Oncology
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology
state: Texas
city: Garland
country: United States
facility: Texas Oncology
state: Texas
city: Longview
country: United States
facility: Texas Oncology
state: Texas
city: Midland
country: United States
facility: Texas Oncology
state: Texas
city: Odessa
country: United States
facility: Texas Oncology
state: Texas
city: Tyler
country: United States
facility: Texas Oncology
state: Texas
city: Fairfax
country: United States
facility: Fairfax Northern Virginia Hematology-Oncology
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Burien
country: United States
facility: Highline Medical Oncology
state: Washington
city: Spokane
country: United States
facility: Cancer Care Northwest
state: Washington
city: Yakima
country: United States
facility: Yakima Valley Memorial Hospital/North Star Lodge
state: Washington
Study officials:
affiliation: Rocky Mountain Cancer Centers
name: Samir Witta, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Texas Oncology - Sammons Cancer Center
name: Kartik Konduri, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dayton Oncology
name: Robert Raju, MD
role: PRINCIPAL_INVESTIGATOR
References: