| Eligibility |
Inclusion Criteria:
- 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)
- 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
Exclusion Criteria:
- 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
- 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-?
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
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