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

NCT04631029 | Completed Phase 1 Results DMC FDA Drug

• 3 other identifiers: NCI-2020-0991610399UM1CA186691
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 5

Brief 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). 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.

Conditions

Extensive Stage Lung Small Cell Carcinoma; Malignant Solid Neoplasm; Metastatic Malignant Neoplasm in the Brain

Outcome Measures

Primary Outcomes (3)

• 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.

  Up to 21 days

• 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.

  Up to 30 days

• 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.

  Up to cycle 4 (1 cycle = 21 days)

Secondary Outcomes (1)

• Progression Free Survival (PFS) Rate

  Up to 2 months

Study Arms (1)

Treatment (carboplatin, etoposide, atezolizumab, entinostat)

EXPERIMENTAL

INDUCTION 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.

Biological: Atezolizumab; Drug: Carboplatin; Drug: Entinostat; Drug: Etoposide

Interventions

Atezolizumab BIOLOGICAL

Given IV

Also known as: MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, Tecentriq

Treatment (carboplatin, etoposide, atezolizumab, entinostat)

Carboplatin DRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, JM8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Treatment (carboplatin, etoposide, atezolizumab, entinostat)

Entinostat DRUG

Given PO

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

Treatment (carboplatin, etoposide, atezolizumab, entinostat)

Etoposide DRUG

Given IV

Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16, VP 16-213, VP 16213, VP-16, VP-16-213, VP16

Treatment (carboplatin, etoposide, atezolizumab, entinostat)

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 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
• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (5)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States

Location

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

• 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.

  PMID: 37555284 DERIVED

MeSH Terms

Conditions

Brain Neoplasms

Interventions

atezolizumab; Carboplatin; entinostat; Etoposide

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Results Point of Contact

• Title: Grants Administrative Manager
• Organization: Johns Hopkins University

JHCCCRO@jhmi.edu

4439273568

Study Officials

• Ryan D Gentzler

  JHU Sidney Kimmel Comprehensive Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: November 14, 2020
• First Posted: November 17, 2020
• Study Start: April 27, 2021
• Primary Completion: December 30, 2021
• Study Completion: July 11, 2023
• Last Updated: October 3, 2025
• Results First Posted: June 27, 2023

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

US (5)