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

Syndax Pharmaceuticals

Status and phase: Completed; Phase 2; Phase 1

Conditions: Non-Small-Cell Lung Carcinoma; Carcinoma, Non-Small Cell Lung

Treatments: Drug: Entinostat; Drug: Placebo; Drug: Erlotinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT00602030

SNDX-275-0401

Details and patient eligibility

About

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).

Enrollment: 141 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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141 participants in 5 patient groups, including a placebo group

Lead-in Phase: Erlotinib + Entinostat 5 mg

Experimental group

Description:

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.

Treatment:

Drug: Erlotinib

Drug: Entinostat

Lead-in Phase: Erlotinib + Entinostat 10 mg

Experimental group

Description:

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.

Treatment:

Drug: Erlotinib

Drug: Entinostat

Double-blind Phase: Erlotinib + Entinostat 10 mg

Experimental group

Description:

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.

Treatment:

Drug: Erlotinib

Drug: Entinostat

Double-blind Phase: Erlotinib + Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Erlotinib

Drug: Placebo

Crossover Phase: Erlotinib + Entinostat 10 mg

Experimental group

Description:

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.

Treatment:

Drug: Erlotinib

Drug: Entinostat