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Extensive Stage Lung Small Cell CarcinomaPhase 1NCT04631029

Testing the Addition of an Anti-cancer Drug, Entinostat, to the Usual Chemotherapy and Immunotherapy Treatment (Atezolizumab, Carboplatin and Etoposide) for Previously Untreated Aggressive Lung Cancer That Has Spread

A Phase 1 study testing Atezolizumab, Carboplatin and Entinostat in people with Extensive Stage Lung Small Cell Carcinoma and Malignant Solid Neoplasm, 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
Search all trials

Trial summary

This phase I trial seeks to find out the best dose, possible benefits and/or side effects of entinostat in combination with atezolizumab, carboplatin and etoposide for the treatment of previously untreated aggressive lung cancer that has spread (extensive-stage small cell lung cancer). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Atezolizumab, Carboplatin and Entinostat
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
5 sitesUnited States
Study dates
27 Apr 2021to 11 Jul 2023
Phase
Phase 1
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 extensive stage SCLC (ES-SCLC) or other solid tumors for which carboplatin and etoposide are considered appropriate therapy
  • No prior systemic therapy for extensive-stage, metastatic disease. Patients with prior limited stage disease who were treated with chemotherapy and concurrent radiation will be permitted to enroll as long as their previous treatment was 12 months or more prior to study enrollment
  • Patients with treated brain metastases are eligible if they have stable symptoms and no ongoing requirement for corticosteroids as therapy for brain metastases
  • Patients with untreated or progressive brain metastases (active brain metastases) are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first cycle of therapy. There must be no ongoing requirement for corticosteroids as therapy for brain metastases
  • Previous radiation, including whole brain radiation, is allowed >= 7 days of study registration. Stereotactic radiation therapy within 7 days is permitted
  • Patients must have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. At least one measurable lesion should be extra-cranial and outside of any portal of irradiation
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  • Archival tissue must be available, or patients must be willing to undergo a new biopsy to provide pre-treatment tumor sample (no intervening chemotherapy treatment, tissue must be from current extensive-stage/metastatic diagnosis)
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Absolute neutrophil count >= 1,500/mcL
  • Hemoglobin >= 9.0 g/dL
  • Platelets >= 100,000/mcL
  • International normalized ratio (INR) < 1.5
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN). (This does not apply to patients with confirmed Gilbert's syndrome)
  • Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional ULN, (if liver metastases present, can be up to 5 x ULN)
  • Creatinine =< institutional ULN OR glomerular filtration rate (GFR) >= 60 mL/min/1.73 m^2 (by the Cockcroft-Gault equation)
  • Serum sodium >= 130 mmol/L
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better
  • The effects of entinostat on the developing human fetus are unknown. For this reason and because histone deacetylase inhibitor (HDACi) agents as well as other therapeutic agents used in this trial are known to be teratogenic, 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, for the duration of study participation, up to 5 months after the last dose of study treatment. 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. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 5 months after completion of study treatment
  • Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity (IDMC) who have a legally-authorized representative (LAR) and/or family member available will also be eligible

Who cannot join

  • Patients with evidence of leptomeningeal metastases (either by imaging or central nervous system [CNS] fluid findings)
  • Patients who are receiving any other investigational agents
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to entinostat or other agents used in study
  • Patients with uncontrolled intercurrent illness
  • Patients with psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because entinostat is HDACi agent with the potential for teratogenic or abortifacient effects and because of known teratogenic and abortifacient effects of cisplatin and etoposide. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with entinostat, and known risks with cisplatin and etoposide, breastfeeding should be discontinued if the mother is treated with entinostat. These potential risks may also apply to other agents used in this study
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  • Patients with a history of autoimmune disease (notable exceptions include hypothyroidism on thyroid replacement medication, type I diabetes, psoriasis or other cutaneous disease controlled with topical agents and without flare in 12 months requiring other treatment, celiac disease controlled with diet alone)
  • Patients with a history of pulmonary fibrosis (history of radiation pneumonitis/fibrosis in the treatment field is permitted if stable and not requiring supplemental oxygen or corticosteroid use)
  • Patients with prior history of allogeneic bone marrow or solid organ transplant
  • Ongoing use of systemic corticosteroids or immunosuppressive agents within 14 days (inhaled corticosteroids, < 7 day course of prednisone for asthma/chronic obstructive pulmonary disease [COPD] exacerbation, or chronic low-dose supplemental steroids for adrenal insufficiency permitted)
  • Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents.
  • Patients who have received prior treatment with anti-CTLA-4 may be enrolled, provided the following requirements are met:
  • Minimum of 12 weeks from the first dose of anti-CTLA-4 and > 6 weeks from the last dose
  • No history of severe immune-related adverse effects from anti-CTLA-4 (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] grade 3 and 4)
  • Treatment with systemic immunostimulatory agents (including, but not limited to, interferon [IFN]-alpha or interleukin [IL]-2) within 6 weeks prior to study registration
  • Patients taking bisphosphonate therapy for symptomatic hypercalcemia. Use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed
  • Patients requiring treatment with a receptor activator of nuclear factor kappa-Β ligand (RANKL) inhibitor (e.g. denosumab) who cannot discontinue it before treatment with atezolizumab
  • Patients requiring treatment with strong CYP3A inhibitors and inducers who cannot discontinue it before treatment with etoposide
  • Because the list of these agents are constantly changing, it is important to regularly consult a frequently updated list such as Facts and Comparisons or Lexicompt; medical reference texts such as the Physicians' Desk Reference may also provide this information
  • Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  • Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
  • Patients with active tuberculosis (TB) are excluded
  • Suspected or confirmed active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19).
  • Those with a history of COVID-19 are eligible if they meet all of the above eligibility criteria after clearance of COVID-19 by one of the following criteria:
  • 14 days have elapsed since symptom onset, the patient is afebrile, and symptoms are improving for at least 72 hours
  • Have 2 negative specimens collected at least 24 hours apart
  • Severe infections within 2 weeks prior to study registration, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
  • Received oral or intravenous (IV) antibiotics within 1 week prior to study registration. Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible
  • Major surgical procedure within 4 weeks prior to study registration or anticipation of need for a major surgical procedure during the course of the study. Common procedures such as biopsies, port insertions, and thoracenteses are allowed
  • Administration of a live, attenuated vaccine within 4 weeks before study registration or anticipation that such a live, attenuated vaccine will be required during the study or up to 5 months after the last dose of atezolizumab

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • University of Virginia Cancer Center

    Charlottesville, Virginia, 22908

  • University of Wisconsin Carbone Cancer Center

    Madison, Wisconsin, 53792

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • University of Pittsburgh Cancer Institute (UPCI)

    Pittsburgh, Pennsylvania, 15232

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

Other trials in United States

About this study

Official title: A Phase 1 Study of Entinostat in Combination With Atezolizumab / Carboplatin / Etoposide in Previously Untreated Extensive-Stage Small Cell Lung Cancer

This phase I trial seeks to find out the best dose, possible benefits and/or side effects of entinostat in combination with atezolizumab, carboplatin and etoposide for the treatment of previously untreated aggressive lung cancer that has spread (extensive-stage small cell lung cancer). Entinostat and etoposide may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Carboplatin is a chemotherapy drug that attaches to deoxyribonucleic acid (DNA) and may kill tumor cells. Giving entinostat in combination with atezolizumab, carboplatin and etoposide may work better than atezolizumab, carboplatin and etoposide alone.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximum tolerated dose (MTD) of entinostat in combination with carboplatin, etoposide, and atezolizumab.

II. To determine safety and tolerability of adding entinostat to carboplatin / etoposide / atezolizumab for extensive-stage small cell lung cancer (ES-SCLC).

III. To determine the feasibility of administering entinostat concomitantly with atezolizumab, carboplatin, and etoposide as determined by the proportion of patients who receive 3 or more cycles of the combination.

SECONDARY OBJECTIVES:

  1. To observe and record anti-tumor activity. II. To determine the proportion of patients who are alive and without disease progression at 9 months (9 month progression free survival [PFS]) after starting entinostat, carboplatin, etoposide, and atezolizumab.

EXPLORATORY OBJECTIVES:

  1. To estimate the clinical activity of entinostat plus carboplatin/etoposide/atezolizumab as determined by response rate (RR), progression free survival (PFS), and overall survival (OS).

II. To explore the prevalence of cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) binding protein (CREBBP)/ histone acetyltransferase p300 (EP300) mutations in newly diagnosed ES-SCLC population.

III. To explore the relationship between CREBBP/EP300 mutations and clinical outcomes.

IV. To explore immune biomarkers that may predict response to atezolizumab and entinostat and changes in these biomarkers over the course of study treatment.

  1. To explore entinostat exposure-response relationships with toxicity and clinical outcomes (PFS and OS).

VI. To evaluate baseline atezolizumab clearance as an early biomarker for OS and to assess the relationship between atezolizumab time-varying clearance, cachexia and clinical outcomes (PFS and OS).

OUTLINE: This is a dose-escalation study of entinostat.

INDUCTION THERAPY: Patients receive carboplatin intravenously (IV) over 30-60 minutes on day 1, etoposide IV over 60 minutes on days 1-3, atezolizumab IV over 30-60 minutes on day 1, and entinostat orally (PO) on days 1, 8, and 15. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients receive atezolizumab IV over 30 minutes on day 1 and entinostat PO on days 1, 8, and 15. Treatment repeats every 21 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, every 3 months for 2 years, then every 6 months for 3 years.

Being tested
Atezolizumab, Carboplatin, Entinostat, Etoposide
Medical subject headings
Brain Neoplasms

What participants receive

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

  • AtezolizumabBiological

    Also called MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A

    Given IV

  • CarboplatinDrug

    Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino

    Given IV

  • EntinostatDrug

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

    Given PO

  • EtoposideDrug

    Also called Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar

    Given IV

Study groups in NCT04631029
Study groupRoleWhat they receive
Treatment (carboplatin, etoposide, atezolizumab, entinostat)ExperimentalINDUCTION THERAPY: Patients receive carboplatin IV over 30-60 minutes on day 1, etoposide IV over 60 minutes on days 1-3, atezolizumab IV over 30-60 minutes on day 1, and entinostat PO on days 1, 8, and 15. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive atezolizumab IV over 30 minutes on day 1 and entinostat PO on days 1, 8, and 15. Treatment repeats every 21 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity.
Receives: Biological: Atezolizumab; Drug: Carboplatin; Drug: Entinostat; Drug: Etoposide

What is being measured

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

  1. Number of Participants With Dose Limiting Toxicities

    The Bayesian optimal interval (BOIN) design will be used to find the MTD based on safety as determined by dose limiting toxicities.

    Measured: Up to 21 days

  2. Number of Participants Experiencing Grade 3 and 4 Adverse Events

    Defined by Common Terminology Criteria for Adverse Events version 5.0. Will be summarized by frequency and magnitude.

    Measured: Up to 30 days

  3. Number of Participants Who Received 3 or More Cycles of the Combination of Entinostat, Atezolizumab, Carboplatin, and Etoposide

    The proportion of participants who received 3 or more cycles of the combination, will be calculated with a 90% confidence interval.

    Measured: Up to cycle 4 (1 cycle = 21 days)

Secondary outcomes (1)

  1. Progression Free Survival (PFS) Rate

    Defined as the proportion of patients alive and without disease progression. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), 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. Will be estimated with a 90% confidence interval. The Kaplan Meier estimator will be used to estimate survival curves.

    Measured: Up to 2 months

Timeline

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

  1. First posted17 Nov 2020
  2. Study start27 Apr 2021
  3. Primary completion30 Dec 2021
  4. Study completion11 Jul 2023

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04631029
Sponsor's protocol ID
NCI-2020-09916
Other IDs
NCI-2020-09916, 10399, 10399, UM1CA186691
Status last verified
Sep 2025
First submitted
14 Nov 2020
Last updated
3 Oct 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Publications

  • Gentzler RD, Villaruz LC, Rhee JC, Horton B, Mock J, Hanley M, Kim K, Rudek MA, Phelps MA, Carducci MA, Piekarz R, Park KS, Bullock TN, Rudin CM. Phase I Study of Entinostat, Atezolizumab, Carboplatin, and Etoposide in Previously Untreated Extensive-Stage Small Cell Lung Cancer, ETCTN 10399. Oncologist. 2023 Nov 2;28(11):1007-e1107. doi: 10.1093/oncolo/oyad221.

    PubMed 37555284

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Atezolizumab, Carboplatin and Entinostat in people with Extensive Stage Lung Small Cell Carcinoma and Malignant Solid Neoplasm, 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 23 inclusion and 31 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 3 Oct 2025. 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 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.

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 27 Jun 2023). 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?

Number of Participants With Dose Limiting Toxicities (time frame: Up to 21 days). The study lists 3 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 NCT04631029, 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 3 Oct 2025.

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