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Recurrent Non-Small Cell Lung CarcinomaPhase 1/2NCT00387465

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

A Phase 1/2 study testing Azacitidine 30mg/m2, Entinostat and Azacitidine 40mg/m2 in people with Recurrent Non-Small Cell Lung Carcinoma and Stage IIIA Non-Small Cell Lung Cancer, run by National Cancer Institute (NCI) at 5 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Azacitidine 30mg/m2, Entinostat and Azacitidine 40mg/m2
Could I receive a placebo?
No, everyone receives an active treatment
How many people
94 participants
Where
5 sitesUnited States
Study dates
Aug 2006to Nov 2014
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 14Show fewer
  • 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

Who cannot join

  • 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

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Johns Hopkins Bayview Medical Center

    Baltimore, Maryland, 21224

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital

    Baltimore, Maryland, 21231

  • Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center

    Baltimore, Maryland, 21287

  • USC Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • Sidney Kimmel Cancer Center

    San Diego, California, 92121

Other trials in United States

About this study

Official title: A Phase I/II Study of Entinostat in Combination With 5-Azacytidine in Patients With Recurrent Advanced Non-Small Cell Lung Cancer

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess safety, characterize toxicities, and determine the maximum tolerated dose of 5-AZA (azacitidine) with a fixed-dose of entinostat in patients with recurrent advanced non-small cell lung cancer (NSCLC). (Phase I) II. To determine the objective response rate of 5-AZA and entinostat in patients with recurrent NSCLC. (Phase II)

SECONDARY OBJECTIVES:

  1. To determine the pharmacokinetic profile of 5-AZA and entinostat in patients with recurrent NSCLC.

II. To assess the pharmacodynamic effects of 5-AZA and entinostat on deoxyribonucleic acid (DNA) methylation, histone acetylation, and gene re-expression in patients with recurrent NSCLC through analysis of blood, sputum and tissue biopsies.

III. To explore the effect of 5-AZA and entinostat on progression-free and overall survival in patients with recurrent advanced non-small cell lung cancer.

IV. To explore the differing response rates and progression-free survivals of two schedules of 5-AZA and entinostat in patients with recurrent advanced non-small cell lung cancer.

OUTLINE: This is a multicenter, phase I, dose-escalation study of azacitidine followed by an open-label, phase II study.

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 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months.

Being tested
Azacitidine 30mg/m2, Entinostat, Azacitidine 40mg/m2
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Azacitidine 30mg/m2Drug

    Also called 5 AZC, 5-AC, 5-Azacytidine, 5-AZC

    Azacitidine 30mg/m2 subcutaneously (SQ)

  • EntinostatDrug

    Also called HDAC inhibitor SNDX-275, MS 27-275, MS-275, SNDX-275

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

  • Azacitidine 40mg/m2Drug

    Also called 5 AZC, 5-AC, 5-Azacytidine, 5-AZC

    Azacitidine 40mg/m2 SQ

Study groups in NCT00387465
Study groupRoleWhat they receive
Phase I - 30mg/m2 AzacitidineExperimentalPatients receive Azacitidine 30mg/m2 SQ and entinostat 7mg PO on days 3 and 10 of each cycle.
Receives: Drug: Azacitidine 30mg/m2; Drug: Entinostat
Phase I - 40mg/m2 AzacitidineExperimentalPatients receive azacitidine 40mg/m2 SQ and entinostat 7mg PO on days 3 and 10 of each cycle.
Receives: Drug: Entinostat; Drug: Azacitidine 40mg/m2
Phase II ArmExperimentalPatients 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.
Receives: Drug: Entinostat; Drug: Azacitidine 40mg/m2

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. (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

    Measured: Up to 28 days

  2. (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.

    Measured: Up to 8 years

Secondary outcomes (9)

  1. Effect of Entinostat and Azacitidine on DNA Methylation and Response

    Number of participants with decrease in DNA methylation ("methylation-signature positive") on Day 10 or Day 29, and either stable disease or objective response (OR) as defined by RECIST 1.0. 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, complete response is defined as disappearance of all target lesions; OR=CR+PR.

    Measured: Baseline and days 10 and 29

  2. 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

    Number of participants with progressive disease (PD), stable disease (SD), or partial response (PR), as defined by Response Evaluation Criteria in Solid Tumors (RECIST 1.0) after at least 1 cycle of subsequent chemotherapy. 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.

    Measured: Up to 8 years

  3. Overall Survival

    Determined by the method determined by Kaplan and Meier. 95% confidence intervals will be estimated.

    Measured: Up to 1 year

  4. Pharmacokinetic Profile of Azacytidine as Measured by Tmax

    Time to maximal concentration of azacitidine in the blood.

    Measured: Day 1

  5. Progression-free Survival

    Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), 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. Determined by the method determined by Kaplan and Meier. 95% confidence intervals will be estimated.

    Measured: Up to 1 year

  6. Pharmacokinetic Profile of Azacitidine as Measured by Cmax

    Maximal concentration (ng/mL) of azacitidine

    Measured: Day 1

  7. Pharmacokinetic Profile of Azacitidine as Measured by AUC (ng*hr/mL)

    Measured: Day 1

  8. Average Steady State Trough Concentration (ng/mL) of Entinostat

    Measured: Day 10 and 17

  9. Pharmacokinetic Profile of Azacitidine as Measured by Half-life

    Measured: Day 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Oct 2006 (estimated)
  2. Study startAug 2006
  3. Primary completionMay 2014
  4. Study completionNov 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
94 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00387465
Sponsor's protocol ID
NCI-2009-00220
Other IDs
NCI-2009-00220, CDR0000504083, NA_00003114, J0658, 7759, P30CA006973, U01CA070095
Status last verified
Apr 2019
First submitted
12 Oct 2006
Last updated
9 May 2019

Publications

  • 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.

    PubMed 22586682

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Azacitidine 30mg/m2, Entinostat and Azacitidine 40mg/m2 in people with Recurrent Non-Small Cell Lung Carcinoma and Stage IIIA Non-Small Cell Lung Cancer, run by National Cancer Institute (NCI) at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 May 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 May 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

(Phase I) Maximum Tolerated Dose (MTD) of Azacitidine When Given Together With Entinostat as Determined by Number of Participants Experiencing Dose-limiting Toxicity (DLT) (time frame: Up to 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00387465, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2019; AzTrials last refreshed its copy on 7 Nov 2026.

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