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

NCT00602030 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: SNDX-275-0401
• Study Type: interventional
• Target: 141
• Locations: 1 country
• Sites: 30

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).

Conditions

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

Keywords

lung cancer; NSCLC; lung neoplasms; respiratory

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (14)

• Objective Response Rate (ORR) in the Double-blind Phase

  Month 6

• 6-Month PFS Rate in the Double-blind Phase

  Month 6

• 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)

• 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)

• 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)

Study Arms (5)

Lead-in Phase: Erlotinib + Entinostat 5 mg

EXPERIMENTAL

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.

Drug: Entinostat; Drug: Erlotinib

Lead-in Phase: Erlotinib + Entinostat 10 mg

EXPERIMENTAL

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.

Drug: Entinostat; Drug: Erlotinib

Double-blind Phase: Erlotinib + Entinostat 10 mg

EXPERIMENTAL

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.

Drug: Entinostat; Drug: Erlotinib

Double-blind Phase: Erlotinib + Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo; Drug: Erlotinib

Crossover Phase: Erlotinib + Entinostat 10 mg

EXPERIMENTAL

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.

Drug: Entinostat; Drug: Erlotinib

Interventions

Entinostat DRUG

Entinostat tablets on Days 1 and 15 of a 28-day cycle.

Also known as: SNDX-275

Crossover Phase: Erlotinib + Entinostat 10 mg; Double-blind Phase: Erlotinib + Entinostat 10 mg; Lead-in Phase: Erlotinib + Entinostat 10 mg; Lead-in Phase: Erlotinib + Entinostat 5 mg

Placebo DRUG

Placebo-matching entinostat tablets on Days 1 and 15 of a 28-day cycle.

Double-blind Phase: Erlotinib + Placebo

Erlotinib DRUG

Erlotinib 150 mg tablets once daily.

Also known as: Tarceva

Crossover Phase: Erlotinib + Entinostat 10 mg; Double-blind Phase: Erlotinib + Entinostat 10 mg; Double-blind Phase: Erlotinib + Placebo; Lead-in Phase: Erlotinib + Entinostat 10 mg; Lead-in Phase: Erlotinib + Entinostat 5 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Syndax Pharmaceuticals: lead

Study Sites (30)

HOPE (Hematology Oncology Physicians & Extenders)

Tucson, Arizona, United States

Location

Rocky Mountain Cancer Center

Denver, Colorado, United States

Location

Advanced Medical Specialties

Miami, Florida, United States

Location

Ocala Oncology Center

Ocala, Florida, United States

Location

Cancer Centers of Florida

Ocoee, Florida, United States

Location

Hematology Oncology Associates of Illinois

Chicago, Illinois, United States

Location

Central Indiana Cancer Centers

Indianapolis, Indiana, United States

Location

Kansas City Cancer Centers

Overland Park, Kansas, United States

Location

Alliance Hematology Oncology

Westminster, Maryland, United States

Location

St Joseph Oncology

Saint Joseph, Missouri, United States

Location

The Center for Cancer Care & Research

St Louis, Missouri, United States

Location

Mahonig Valley Hematology Oncology Associates

Boardman, Ohio, United States

Location

Dayton Oncology & Hematology

Kettering, Ohio, United States

Location

Oncology Associates of Oregon

Eugene, Oregon, United States

Location

Texas Oncology

Amarillo, Texas, United States

Location

Texas Oncology

Austin, Texas, United States

Location

Texas Oncology

Bedford, Texas, United States

Location

Texas Oncology, Sammons Cancer Center

Dallas, Texas, United States

Location

Texas Oncology

Dallas, Texas, United States

Location

Texas Oncology

Fort Worth, Texas, United States

Location

Texas Oncology

Garland, Texas, United States

Location

Texas Oncology

Longview, Texas, United States

Location

Texas Oncology

Midland, Texas, United States

Location

Texas Oncology

Odessa, Texas, United States

Location

Texas Oncology

Tyler, Texas, United States

Location

Fairfax Northern Virginia Hematology-Oncology

Fairfax, Virginia, United States

Location

Virginia Oncology Associates

Norfolk, Virginia, United States

Location

Highline Medical Oncology

Burien, Washington, United States

Location

Cancer Care Northwest

Spokane, Washington, United States

Location

Yakima Valley Memorial Hospital/North Star Lodge

Yakima, Washington, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

entinostat; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Michael Meyers, MD, PhD, Chief Medical Officer
• Organization: Syndax Pharmaceuticals, Inc.

mmeyers@syndax.com

+1-646-690-7620

Study Officials

• Samir Witta, MD

  Rocky Mountain Cancer Centers

  PRINCIPAL INVESTIGATOR

• Kartik Konduri, MD

  Texas Oncology - Sammons Cancer Center

  PRINCIPAL INVESTIGATOR

• Robert Raju, MD

  Dayton Oncology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2008
• First Posted: January 28, 2008
• Study Start: January 8, 2008
• Primary Completion: February 4, 2010
• Study Completion: February 1, 2012
• Last Updated: August 22, 2022
• Results First Posted: June 28, 2022

Record last verified: 2022-08

Locations

US (30)