Azacitidine and Entinostat Before Chemotherapy in Treating Patients With Advanced Non-small Cell Lung Cancer

Stage IV Non-Small Cell Lung Cancer Clinical Trial

Official title:

A Randomized Phase II Trial of Cytotoxic Chemotherapy With or Without Epigenetic Priming in Patients With Advanced Non-Small Cell Lung Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01935947
• Other study ID #: NCI-2013-00949
• Secondary ID: NCI-2013-00949NA
• Status: Terminated
• Phase: Phase 2
• Start date: May 2013
• Est. completion date: April 2017

Study information

• Verified date: June 2018
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized phase II trial studies how well azacitidine and entinostat before chemotherapy works in treating patients with non-small cell lung cancer that has spread to other places in the body. Drugs used in chemotherapy, such as azacitidine, irinotecan hydrochloride, gemcitabine hydrochloride, docetaxel, and pemetrexed disodium, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Entinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving azacitidine and entinostat before chemotherapy may work better in treating patients with non-small cell lung cancer.

Description:

PRIMARY OBJECTIVES:

I. Percentage of patients progression-free at 6 months from time of randomization.

SECONDARY OBJECTIVES:

I. Progression-free survival (PFS). II. Overall survival (OS).

OUTLINE: Patients are randomized to 1 of 3 treatment arms.

ARM A: Patients receive azacitidine subcutaneously (SC) on days 1-6 and 8-10 and entinostat orally (PO) on days 3 and 10. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or progressive disease receive chemotherapy of the treating oncologist's choice comprising irinotecan hydrochloride intravenously (IV) on day 1, docetaxel IV on day 1, pemetrexed disodium IV on day 1, or gemcitabine hydrochloride IV on days 1 and 8. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive azacitidine PO on days 1-21 and entinostat PO on days 3 and 10. Treatment repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or progressive disease receive chemotherapy of the treating oncologist's choice as in Arm A.

ARM C: Patients receive chemotherapy of the treating oncologist's choice as in Arm A.

After completion of treatment, patients are followed up every 3-6 months for 24 months and then yearly thereafter.

Other known NCT identifiers

• NCT01846897

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 17
• Est. completion date: April 2017
• Est. primary completion date: April 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients must have histologically or cytologically proven non-small cell lung cancer; tumor tissue must be available from all patients prior to initiation of protocol therapy, either from original diagnostic biopsy, or biopsy performed prior to initiation of protocol therapy

• 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 for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam

• Patients must have received 1 prior platinum containing doublet regardless of mutation status

• Patients with targetable mutation i.e. epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK), must have been treated with at least 1 prior tyrosine kinase inhibitor (TKI)

• Prior immunotherapy is allowed

• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Karnofsky >= 70%)

• Life expectancy of greater than 12 weeks

• Leukocytes >= 3,000/mcL

• Absolute neutrophil count >= 1,500/mcL

• Platelets >= 100,000/mcL

• Total bilirubin within normal institutional limits

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transferase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transferase [SGPT]) =< 2.5 X institutional upper limit of normal

• Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^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 she or her partner is participating in this study, she should inform her treating physician immediately

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• 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 who are 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 may be treated with steroids as clinically indicated

• 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, azacitidine, mannitol, irinotecan, docetaxel, pemetrexed, or gemcitabine, or other agents used in the study

• Uncontrolled inter-current illness including, but not limited to, ongoing or active infection, New York Heart Association (NYHA) class 3-4 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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Azacitidine
Given SC
• Azacitidine
Given PO
• Docetaxel
Given IV
• Entinostat
Given PO
• Gemcitabine Hydrochloride
Given IV
• Irinotecan Hydrochloride
Given IV

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Pemetrexed Disodium
Given IV

Locations

Country	Name	City	State
United States	Johns Hopkins Bayview Medical Center	Baltimore	Maryland
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	Medical University of South Carolina	Charleston	South Carolina
United States	USC / Norris Comprehensive Cancer Center	Los Angeles	California
United States	USC Norris Oncology/Hematology-Newport Beach	Newport Beach	California

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Genome-wide Techniques, Including Expression Array and Methylation Array	Expression array and methylation array will be compared to response.	After 1 month of therapy
Other	Predictive and Prognostic Value of the Previously Defined Epigenetic Signature, Comprised of Promoter Methylation Analysis of 4 Target Genes		After 1 month of therapy
Other	Response to Therapy Compared to Genetic and Epigenetic Factors and Tested for Association		After 1 month of therapy
Primary	Percentage of Patients Progression-free at 6 Months From the Time of Randomization	The final analysis will be by Fisher's Exact test, with percentage of patients who have not progressed as the outcome variable. Using Fisher's Exact test for analysis with 55 patients per treatment group will provide 88% power to detect an increase from 40% (chemotherapy alone) to 65% (epigenetic therapy followed by chemotherapy) in the number of patients who are progression free at six months.	At 6 months
Secondary	Overall Survival (OS)		From the time of enrollment to trial until death, assessed up to 2 years
Secondary	Progression Free Survival	From the time of randomization until radiologic or clinical progression is noted, assessed up to 2 years.	up to 2 years