| Eligibility |
Inclusion Criteria:
1. Written informed consent and HIPAA authorization for release of personal health
information prior to registration. NOTE: HIPAA authorization may be included in the
informed consent or obtained separately.
2. Age = 18 years with ability and willingness to provide informed consent.
3. ECOG Performance Status of 0-2.
4. Histological confirmation of Small Cell Lung Cancer- Extensive Stage (SCLC) per
Veterans Administration Lung Study Group (VALG).
5. At least one untreated asymptomatic brain metastasis that is measurable by RECIST 1.1
that has not been previously irradiated.
6. No prior treatment for metastatic disease. EXCEPTION: A single cycle of chemotherapy
(platinum/etoposide) with or without atezolizumab is allowed within 30 days prior to
enrollment.
7. Treatment-free for at least 6 months since last chemo/radiotherapy, among those
treated (with curative intent) with prior chemo/radiotherapy for limited-stage SCLC.
8. Any prior cancer treatment must be completed at least 6 months prior to registration
and the subject must have recovered from all reversible acute toxic effects of the
regimen (other than alopecia) to Grade = 1 or baseline. NOTE: a single cycle of
chemotherapy (platinum/etoposide) with or without atezolizumab is allowed within 30
days prior to enrollment. NOTE: Extracranial radiation is allowed.
9. A concurrent diagnosis of a separate malignancy is allowed if clinically stable and
does not require tumor-directed therapy.
10. Demonstrate adequate organ function as defined in the table below
- Absolute Neutrophil Count (ANC) = 1.5K/mm3 without GCSF
- Hemoglobin (Hgb) = 9 g/dL (without transfusion)
- Lymphocyte Count: = 500/µL
- Platelet Count: = 100,000/µL without transfusion
- Calculated creatinine clearance = 50 cc/min OR Serum Cr < 1.5 x institutional ULN
- Bilirubin = 1.5 × upper limit of normal (ULN)
- Aspartate aminotransferase (AST) = 2 × ULN without liver metastasis = 5 × ULN
with liver metastasis
- Alanine aminotransferase (ALT) = 2 × ULN without liver metastasis = 5 × ULN with
liver metastasis
11. Females of childbearing potential must have a negative serum pregnancy test within 3
days (72 hours) prior to enrollment. NOTE: Females are considered of childbearing
potential unless they are surgically sterile (have undergone a hysterectomy or
bilateral oophorectomy) or they are naturally postmenopausal for at least 12
consecutive months.
12. Females of childbearing potential and males must be willing to abstain from
heterosexual activity or to use 2 forms of effective methods of contraception,
including at least one method with a failure of < 1% per year, from the time of
informed consent until 150 days (5 months) after treatment discontinuation.
13. Negative hepatitis B surface antigen (HBsAg) test, negative total hepatitis B core
antibody (HBcAb) test, or positive total HBcAb test followed by a negative hepatitis B
virus (HBV) DNA test. The HBV DNA test will be performed only for patients who have a
positive total HBcAb test. Testing required at screening only if results are not
known.
14. Negative hepatitis C virus (HCV) antibody test, or positive HCV antibody test followed
by a negative HCV RNA test. The HCV RNA test will be performed only for patients who
have a positive HCV antibody test. A positive HCV RNA test is sufficient to diagnose
active HCV infection in the absence of an HCV antibody test.
15. As determined by the enrolling physician or protocol designee, ability of the subject
to understand and comply with study procedures.
Exclusion Criteria:
1. Known active CNS metastases which are symptomatic. CNS metastases are considered
asymptomatic if the patient does not require high dose or escalating corticosteroids
or anticonvulsant therapy. Steroid dose must be equivalent to 2 mg of dexamethasone or
less daily.
- Prior steroid use as part of an anti-emetic regimen with chemotherapy is allowed.
- Patients must be on a stable dose of corticosteroid. No tapering or decreasing
dose within 7 days of enrollment.
2. Leptomeningeal disease. Discrete dural-based metastases will be allowed without
evidence of leptomeningeal disease.
3. Radiation therapy within 14 days prior to Day 1 of Cycle 1 Day 1. NOTE: Extracranial
radiation is allowed.
4. Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium > 12
mg/dL or corrected serum calcium > ULN)
5. Known auto-immune conditions requiring systemic immune suppression therapy other than
prednisone < 10 mg daily (or equivalent).
6. History of interstitial pneumonitis from any cause.
7. Concurrent severe and/or uncontrolled medical conditions which may compromise
participation in the study as assessed by site investigator.
8. Current active infectious disease requiring systemic antibiotics, antifungal, or
antiviral treatment on Cycle 1 Day 1. Patients receiving prophylactic antibiotics
(e.g., for prevention of urinary tract infection or chronic obstructive pulmonary
disease) are eligible. NOTE: Subjects with active tuberculosis are NOT eligible.
9. Current use of medications specified by the protocol as prohibited for administration
in combination with the study drugs. This includes patients with a condition requiring
systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents)
or other immunosuppressive medications within 14 days prior to Cycle 1 Day 1. Inhaled
or topical steroids and adrenal replacement doses >10 mg daily prednisone equivalents
are permitted in the absence of active autoimmune disease. Patients who are receiving
denosumab prior to enrollment must be willing and eligible to receive a bisphosphonate
instead.
10. History of myocardial infarction, NYHA class II or greater congestive heart failure,
or unstable angina, cardiac or other vascular stenting, angioplasty, or surgery within
6 months prior to study enrollment.
11. Known history of HIV seropositivity or known acquired immunodeficiency syndrome
(AIDS), Testing not required at screening.
12. Requirement for ongoing anticoagulation with heparin, low molecular weight heparin, or
other oral anticoagulant (coumadin, DOAC).
13. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
drainage procedures (once monthly or more frequently). NOTE: Patients with indwelling
catheters (e.g., PleurX®) are allowed.
14. History of severe allergic, anaphylactic, or other hypersensitivity reactions to
chimeric or humanized antibodies or fusion proteins.
15. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster
ovary cells or any component of the atezolizumab formulation.
16. History of allergic reactions to carboplatin or etoposide.
17. Intolerance of atezolizumab or other PD-1/PD-L1 axis drug(s), or any other antibody or
drug specifically targeting T-cell co-stimulation or immune checkpoint pathways,
including prior therapy with anti-tumor vaccines or other immune-stimulatory
anti-tumor agents.
18. Active or history of autoimmune disease or immune deficiency, including, but not
limited to, myasthenia gravis, myositis, autoimmune hepatitis, inflammatory bowel
disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome,
Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions:
- Patients with a history of autoimmune-related hypothyroidism who are on
thyroid-replacement hormone are eligible for the study.
- Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen
are eligible for the study.
- Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with
dermatologic manifestations only (e.g., patients with psoriatic arthritis are
excluded) are eligible for the study provided all of following conditions are
met:
- Rash must cover < 10% of body surface area
- Disease is well controlled at baseline and requires only low-potency topical
corticosteroids
- There has been no occurrence of acute exacerbations of the underlying
condition requiring psoralen plus ultraviolet A radiation, methotrexate,
retinoids, biologic agents, oral calcineurin inhibitors
19. Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study
treatment, or anticipation of need for such a vaccine during atezolizumab treatment or
within 5 months after the final dose of atezolizumab.
20. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the
mother is being treated on study).
21. Treatment with any investigational drug within 28 days prior to Cycle 1 Day 1.
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