Inclusion Criteria:
- Written informed consent and Health Insurance Portability and Accountability Act
(HIPAA) authorization for release of personal health information
- NOTE: HIPAA authorization may be included in the informed consent or obtained
separately
- Age >= 18 years at the time of consent
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 28 days
prior to registration
- Have histologically or cytologically-documented diagnosis of extensive stage (i.e.
metastatic and/or recurrent) small cell lung cancer and have progressed or recurred
after platinum-based chemotherapy with immunotherapy. Eligible patients will be
defined as follows:
- "Sensitive" Disease: Patients who had one previous line of chemotherapy and
relapsed after > 90 days of completion of treatment
- "Resistant" Disease: Patients with no response to first-line chemo-immunotherapy
or progression < 90 days after completing treatment
- Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST)
v1.1 within 28 days prior to registration
- Maximum of 1 prior line of therapy is allowed in the setting of metastatic disease.
Patients who recur after treatment for limited state disease, and who receive first
line metastatic treatment with chemo-immunotherapy would be considered eligible upon
progression on chemo-IO in the metastatic setting
- Absolute neutrophil count (ANC) >= 1.5 K/mm^3 (obtained within 28 days prior to
registration)
- Platelets >= 100,000 / mcL (obtained within 28 days prior to registration)
- Serum creatinine =< 2.0 X upper limit of normal (ULN) OR measured or calculated
creatinine clearance (glomerular filtration rate [GFR] can also be used in place of
creatinine or creatinine clearance [CrCl]) >= 50 mL/min as estimated by Cockcroft and
Gault formula for subject with creatinine levels > 2 x institutional ULN (obtained
within 28 days prior to registration)
- Bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin
levels > 1.5 ULN
- Patients with known Gilbert disease: serum bilirubin =< 3 x ULN) (obtained within
28 days prior to registration)
- Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) =< 3 X ULN OR =< 5
X ULN for subjects with liver metastases (obtained within 28 days prior to
registration)
- Albumin > 2.5 mg/dL (obtained within 28 days prior to registration)
- International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN for
patients not receiving therapeutic anticoagulation (obtained within 28 days prior to
registration)
- For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
- Activated partial thromboplastin time (aPTT) =< 1.5 x ULN for patients not receiving
therapeutic anticoagulation (obtained within 28 days prior to registration)
- For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
- Females of childbearing potential must have a negative serum or urine pregnancy test
within 14 days prior to registration
- For women of childbearing potential: agreement to remain abstinent (refrain from
vaginal intercourse) or use contraceptive methods and agreement to refrain from
donating eggs, as defined below:
- Women must remain abstinent or use contraceptive methods with a failure rate of <
1% per year during the treatment period and for 5 months after the final dose of
atezolizumab or temozolomide. Women must refrain from donating eggs during this
same period
- Examples of contraceptive methods with a failure rate of < 1% per year include
bilateral tubal ligation, male sterilization, hormonal contraceptives that
inhibit ovulation, hormone releasing intrauterine devices, and copper
intrauterine devices
- The reliability of sexual abstinence should be evaluated in relation to the
duration of the clinical trial and the preferred and usual lifestyle of the
patient. Periodic abstinence (e.g., calendar, ovulation, sympto-thermal, or post
ovulation methods) and withdrawal are not adequate methods of contraception
- For men able to father a child: agreement to remain abstinent (refrain from vaginal
intercourse) or use a condom, and agreement to refrain from donating sperm, as defined
below:
- With a female partner of childbearing potential or pregnant female partner, men
must remain abstinent or use a condom during the treatment period and for 3
months after the final dose of temozolomide to avoid exposing the embryo. Men
must refrain from donating sperm during this same period
- The reliability of sexual abstinence should be evaluated in relation to the
duration of the clinical trial and the preferred and usual lifestyle of the
patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or
postovulation methods) and withdrawal are not adequate methods of contraception
- As determined by the enrolling physician or protocol designee, ability of the subject
to understand and comply with study procedures for the entire length of the study
- Availability of archival tissue, preferably a recent formalin-fixed, paraffin-embedded
(FFPE) tumor tissue block. A recently obtained archival FFPE tumor tissue block from a
primary or metastatic tumor resection or biopsy can be provided if it was obtained
within 1 year of trial screening. Patients with tumor specimens older than 1 year may
still be eligible if deemed so by study sponsor. For eligibility, only confirmation of
archival tissue is needed. Verification of tumor burden in the biopsy is encouraged.
For optimal biomarker results, tumor content should be > 30% of total tissue area
- Be willing to provide peripheral blood samples at specified time-points during the
study
- Life expectancy greater than 3 months as determined by the enrolling physician or
protocol designee
- Ability to swallow and retain oral medication
Exclusion Criteria:
- Is currently participating and receiving study therapy or has participated in a study
of an investigational agent and received study therapy or used an investigational
device within 4 weeks of the first dose of treatment
- Has received prior temozolomide therapy
- Patients with a prior or concurrent malignancy whose natural history or treatment has
the potential to interfere with the safety or efficacy assessment of the
investigational regimen are not eligible for this trial
- Symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis.
Subjects with asymptomatic lesions will be eligible if considered appropriate by the
treating physician
- NOTE: Subjects who are symptomatic and have not undergone prior brain imaging
must undergo a head computed tomography (CT) scan or brain MRI within 28 days
prior to registration to exclude brain metastases
- NOTE: A subject with prior brain metastasis may be considered if they have
completed their treatment for brain metastasis at least 2 weeks prior to study
registration, have been off corticosteroids for ≥ 2 weeks, and are asymptomatic
- Clinically significant acute infection requiring systemic antibacterial, antifungal,
or antiviral therapy including:
- Tuberculosis (clinical evaluation that includes clinical history, physical
examination, and radiographic findings, and TB testing in line with local
practice)
- Hepatitis B (known positive HBV surface antigen [HBsAg] result)
- Hepatitis C, or
- Human immunodeficiency virus (positive HIV 1/2 antibodies)
- NOTES: Patients with a past or resolved HBV infection (defined as the presence of
hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. In
patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV
viral load must be undetectable on suppressive therapy, if indicated. Patients
positive for hepatitis C (HCV) antibody are eligible only if polymerase chain
reaction is negative for HCV ribonucleic acid (RNA). Subjects with HIV/acquired
immunodeficiency syndrome (AIDS) with adequate antiviral therapy to control viral
load (i.e undetectable) would be allowed if they are stable and have been on
treatment for >= 4 weeks prior to first dose of study drug(s). Subjects with
viral hepatitis with controlled viral load would be allowed while on suppressive
antiviral therapy. Testing not required
- Has had prior chemotherapy, immunotherapy, targeted small molecule therapy, or
radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e.,
=< grade 1 or at baseline) from adverse events due to a previously administered agent
- Note: Subjects with =< grade 2 neuropathy or alopecia due to chemotherapy are an
exception to this criterion and may qualify for the study
- Note: If subject received major surgery, they must have recovered adequately from
the toxicity and/or complications from the intervention prior to starting therapy
- Note: Subjects with irreversible toxicity that in the opinion of the treating
physician is not reasonably expected to be exacerbated by the investigational
product may be included (e.g., hearing loss, hormone deficiency requiring
replacement therapy)
- Active or history of autoimmune disease or immune deficiency, including, but not
limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus
erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid
antibody syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome,
or multiple sclerosis, with the following exceptions:
- Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not
considered a form of systemic treatment
- 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
- No occurrence of acute exacerbations of the underlying condition requiring
psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic
agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids
within the previous 12 months
- History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of
active pneumonitis on screening chest computed tomography (CT) scan. History of
radiation pneumonitis in the radiation field (fibrosis) is permitted
- Significant cardiovascular disease (such as New York Heart Association Class II or
greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3
months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
- Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial
- Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study
treatment
- Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the
mother is being treated on study)
- Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the subject's
participation for the full duration of the trial, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator
