Azacitidine and Entinostat in Treating Patients With Recurrent Advanced Non-Small Cell Lung Cancer

NCT00387465 | Completed Phase 1 Results

• 7 other identifiers: NCI-2009-00220CDR0000504083NA_00003114J06587759P30CA006973U01CA070095
• Study Type: interventional
• Target: 94
• Locations: 1 country
• Sites: 5

Brief Summary

This phase I/II trial is studying the side effects and best dose of azacitidine when given together with entinostat and to see how well they work in treating patients with recurrent advanced non-small cell lung cancer. Azacitidine and entinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving azacitidine together with entinostat may kill more tumor cells.

Conditions

Recurrent Non-Small Cell Lung Carcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• (Phase I) Maximum Tolerated Dose (MTD) of Azacitidine When Given Together With Entinostat as Determined by Number of Participants Experiencing Dose-limiting Toxicity (DLT)

  DLT is defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0

  Up to 28 days

• (Phase II) Objective Response Rate After Treatment With Azacitidine and Entinostat as Assessed by Number of Participants With Response After at Least One Cycle of Therapy

  Number of participants with progressive disease (PD), stable disease (SD), complete response (CR), or partial response (PR), as defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.0), after completing at least one cycle of therapy. Per RECIST 1.0, progression is defined as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; PR is defined as \>=30% decrease in the sum of the longest diameter of target lesions, CR is defined as the disappearance of all target lesions.

  Up to 8 years

Secondary Outcomes (9)

• Effect of Entinostat and Azacitidine on DNA Methylation and Response

  Baseline and days 10 and 29

• Major Objective Response After Immediate Subsequent Therapy as Measured by Number of Participants With PR, SD, PD After at Least 1 Cycle of Subsequent Chemotherapy

  Up to 8 years

• Overall Survival

  Up to 1 year

• Pharmacokinetic Profile of Azacytidine as Measured by Tmax

  Day 1

• Progression-free Survival

  Up to 1 year

Study Arms (3)

Phase I - 30mg/m2 Azacitidine

EXPERIMENTAL

Patients receive Azacitidine 30mg/m2 SQ and entinostat 7mg PO on days 3 and 10 of each cycle.

Drug: Azacitidine 30mg/m2; Drug: Entinostat

Phase I - 40mg/m2 Azacitidine

EXPERIMENTAL

Patients receive azacitidine 40mg/m2 SQ and entinostat 7mg PO on days 3 and 10 of each cycle.

Drug: Entinostat; Drug: Azacitidine 40mg/m2

Phase II Arm

EXPERIMENTAL

Patients receive azacitidine 40mg/m2 subcutaneously (SQ) on days 1-6 and 8-10 and entinostat 7mg PO on days 3 and 10. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Entinostat; Drug: Azacitidine 40mg/m2

Interventions

Azacitidine 30mg/m2 DRUG

Azacitidine 30mg/m2 subcutaneously (SQ)

Also known as: 5 AZC, 5-AC, 5-Azacytidine, 5-AZC, AZACITIDINE, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, U-18496, Vidaza

Phase I - 30mg/m2 Azacitidine

Entinostat DRUG

7mg by mouth (PO) on days 3 and 10 of each cycle

Also known as: HDAC inhibitor SNDX-275, MS 27-275, MS-275, SNDX-275

Phase I - 30mg/m2 Azacitidine; Phase I - 40mg/m2 Azacitidine; Phase II Arm

Azacitidine 40mg/m2 DRUG

Azacitidine 40mg/m2 SQ

Also known as: 5 AZC, 5-AC, 5-Azacytidine, 5-AZC, AZACITIDINE, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, U-18496, Vidaza

Phase I - 40mg/m2 Azacitidine; Phase II Arm

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or cytologically confirmed metastatic or unresectable NSCLC
• Patient must have failed at least one previous chemotherapy regimen
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>= 20 mm with conventional techniques or as \>= 10 mm with spiral computed tomography (CT) scan
• Life expectancy of greater than 12 weeks
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) =\< 2 (Karnofsky \>= 60%)
• Leukocytes \>= 3,000/mcL
• Absolute neutrophil count \>= 1,500/mcL
• Platelet count \>= 100,000/mcL
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\] and alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase \[SGPT\]) =\< 2.5 x upper limit of normal
• Creatinine within normal institutional limits OR creatinine clearance \>= 60 mL/min/1.73m\^2 for patients with creatinine levels above institutional normal
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Ability to understand and the willingness to sign a written informed consent document
• Patients who have a major objective response to treatment on this protocol, and who experience progression of disease at least 1 year after completion of protocol consent and therapy, may be re-treated at the previously effective dose and schedule

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Patients may not be receiving any other investigational agents
• Patients with uncontrolled brain metastases; patients with brain metastases must have stable neurologic status following local therapy (surgery or radiation) for at least 4 weeks, and must be without neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
• Patients with liver metastases that replace greater than 30% of the liver parenchyma
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to entinostat, 5-AZA, mannitol or other agents used in the study
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated on this protocol
• Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (5)

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Sidney Kimmel Cancer Center

San Diego, California, 92121, United States

Location

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, 21224, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital

Baltimore, Maryland, 21231, United States

Location

Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21287, United States

Location

Related Publications (1)

• Juergens RA, Wrangle J, Vendetti FP, Murphy SC, Zhao M, Coleman B, Sebree R, Rodgers K, Hooker CM, Franco N, Lee B, Tsai S, Delgado IE, Rudek MA, Belinsky SA, Herman JG, Baylin SB, Brock MV, Rudin CM. Combination epigenetic therapy has efficacy in patients with refractory advanced non-small cell lung cancer. Cancer Discov. 2011 Dec;1(7):598-607. doi: 10.1158/2159-8290.CD-11-0214. Epub 2011 Nov 9.

  PMID: 22586682 RESULT

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Azacitidine; entinostat

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: John Wrangle, MD
• Organization: SKCCC

wrangle@musc.edu

843-792-7789

Study Officials

• John Wrangle

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2006
• First Posted: October 13, 2006
• Study Start: August 1, 2006
• Primary Completion: May 1, 2014
• Study Completion: November 1, 2014
• Last Updated: May 9, 2019
• Results First Posted: May 9, 2019

Record last verified: 2019-04

Locations

US (5)