Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical Trial Summary
This phase II/III trial compares the effect of adding radiation therapy to the usual
maintenance therapy with atezolizumab versus atezolizumab alone in patients who have already
received atezolizumab plus chemotherapy for the treatment of small cell lung cancer that has
spread outside of the lung or to other parts of the body (extensive stage). 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. Radiation
therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving radiation
therapy in addition to atezolizumab may extend the time without extensive small cell lung
cancer growing or spreading compared to atezolizumab alone.
Phase
Phase 2/Phase 3
Funding Agency/Sponsor
National Cooperative Group
Disease
Thoracic Oncology
Enrollment Eligibility
Inclusion Criteria:
- Any confirmation (cytologic, histologic, or pathologic) of extensive stage small cell
lung cancer at any site, either primary or metastases
- Partial response (PR) or stable disease (SD) after 4-6 cycles of etoposide/platinum
(E/P) doublet plus atezolizumab by re-staging scans (positron emission tomography
[PET]/computed tomography [CT] scan, diagnostic CT scan, magnetic resonance imaging
[MRI] optional per treating physician); atezolizumab should continue through
randomization. Patients must be randomized within 9 weeks of last dose of
etoposide/platinum (if not receiving PCI) or 6 weeks from completion of prophylactic
cranial irradiation (PCI)
- NOTE: Patients must have at least 3 cycles of E/P plus atezolizumab. They can
have one cycle of induction E/P without concurrent atezolizumab if unable to
receive concurrent E/P combined with atezolizumab for all cycles of induction
therapy
- Patients must have measurable disease (per Response Evaluation Criteria in Solid
Tumors [RECIST]) and 3 or fewer observable liver metastases and no evidence of
progressive disease (per RECIST) at time of enrollment
- At time of enrollment after induction E/P chemotherapy and atezolizumab, if there is a
pleural effusion, patients will be eligible if thoracentesis is cytologically negative
or if pleural fluid is too small a volume to effectively sample by thoracentesis and
does not show increased metabolic activity on CT/PET imaging
- Appropriate stage for study entry based on the following diagnostic workup:
- History/physical examination within 14 days prior to registration;
- Imaging within 42 days prior to registration to include:
- MRI brain with contrast or CT brain with contrast
- CT chest, abdomen and pelvis or whole body PET/CT scan any time after the
fourth cycle of chemotherapy and prior to registration
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 within 14 days
prior to registration
- Absolute neutrophil count (ANC) >= 1,000/cells/mm^3 (within 14 days prior to
registration)
- Platelets >= 75,000 cells/mm^3 (within 14 days prior to registration)
- Hemoglobin >= 8 g/dL (within 14 days prior to registration)
- Total bilirubin =< 1.5 x upper limit of normal (ULN) (within 14 days prior to
registration)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and
alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3.0 x
ULN (AST and/or ALT =< 5 ULN for patients with liver involvement) (within 14 days
prior to registration)
- Alkaline phosphatase =< 2.5 x ULN (=< 5 ULN for patients with documented liver
involvement or bone metastases) (within 14 days prior to registration)
- Adequate renal function = Creatinine clearance >=40 mL/min by the Cockcroft-Gault
(C-G) equation: (within 14 days prior to registration)
- Upfront radiation therapy of symptomatic metastatic site is permissible if causing
symptoms such as pain or impending fracture
- Patients with brain metastases are eligible after receiving whole brain radiation
before enrollment (anytime during induction systemic therapy). Whole brain radiation
can be delivered with hippocampal sparing or 3-D conformal technique. Patients with
irradiated brain metastases are eligible if they are clinically stable from a
neurological standpoint after completing radiotherapy (e.g. not having uncontrolled
seizures) and do not require use of steroids above a dose of 10 mg of prednisone daily
- For women of childbearing potential, a negative serum or urine pregnancy test within
14 days prior to registration.
- Note: Women will be considered post-menopausal if they have been amenorrheic for
12 months without an alternative medical cause. The following age-specific
requirements apply:
- Women < 50 years of age would be considered post-menopausal if they have
been amenorrheic for 12 months or more following cessation of exogenous
hormonal treatments and if they have luteinizing hormone and
follicle-stimulating hormone levels in the post-menopausal range for the
institution or underwent surgical sterilization (bilateral oophorectomy or
hysterectomy)
- Women >= 50 years of age would be considered post-menopausal if they have
been amenorrheic for 12 months or more following cessation of all exogenous
hormonal treatments, had radiation-induced menopause with last menses > 1
year ago, had chemotherapy-induced menopause with last menses > 1 year ago,
or underwent surgical sterilization (bilateral oophorectomy, bilateral
salpingectomy or hysterectomy)
- Patients positive for human immunodeficiency virus (HIV) on effective anti-retroviral
therapy with undetectable viral load within 6 months and a stable regimen of highly
active anti-retroviral (HAART) HIV-positive patients must have no requirement for
concurrent antibiotics or antifungal agents for the prevention of opportunistic
infections
- The patient or a legally authorized representative must provide study-specific
informed consent prior to study entry
Exclusion Criteria:
- Metastatic disease invading the liver (> 3 metastases), heart or > 10 metastatic sites
detectable after induction systemic therapy. Each visible bone metastasis on
radiographic scan counts as one site
- Patients with a concurrent malignancy whose natural history or treatment has the
potential to interfere with the safety or efficacy assessment of the investigational
regimen with atezolizumab or radiation
- Prior radiotherapy in the thorax that would result in overlapping RT fields, unless
the overlapping fields meet acceptable dose constraints for normal tissue
- Active autoimmune disease, including, but not limited to: systemic lupus
erythematosus; rheumatoid arthritis; inflammatory bowel disease (e.g. Crohn's,
ulcerative colitis); vascular thrombosis associated with antiphospholipid syndrome;
Wegener's granulomatosis; Sjogren's syndrome; Guillain-Barre syndrome; multiple
sclerosis; vasculitis; or glomerulonephritis.
- If the autoimmune disease is not active for over 3 years and the patient is not
receiving immunosuppressive treatment such as methotrexate or steroids above a
dose equivalent to 10 mg prednisone daily, the patient is eligible.
- Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid
replacement hormone are eligible
- Patients with controlled type 1 diabetes mellitus on a stable insulin regimen are
eligible
- Patients with eczema, psoriasis, lichen simplex chronicus or vitiligo with
dermatologic manifestations are excluded only if they have active disease with
acute exacerbation and on immunosuppressive medications within the 12 months
prior to enrollment. They are eligible otherwise.
- Severe, active co-morbidity defined as follows:
- Any other diseases, metabolic dysfunction, physical examination finding, or
clinical laboratory finding giving reasonable suspicion of a disease or condition
that contraindicates the use of an investigational drug or that may affect the
interpretation of the results or render the patient at high risk from treatment
complications;
- Active tuberculosis;
- Known clinically significant liver disease, including active viral, alcoholic, or
other hepatitis; cirrhosis; fatty liver; and inherited liver disease
- Patients with past or resolved hepatitis B infection (defined as having a
negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc
[antibody to hepatitis B core antigen] antibody test) are eligible
- Patients positive for hepatitis C virus (HCV) antibody are eligible only if
polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA).
(The HCV RNA test must be performed for patients who have a positive HCV
antibody test)
- Known immunosuppressive disease, for example history of bone marrow transplant or
chronic lymphocytic leukemia (CLL);
- Chronic obstructive pulmonary disease (COPD) requiring chronic oral steroid
therapy of > 10 mg prednisone daily or equivalent at the time of registration.
Inhaled corticosteroids are not exclusionary;
- Unstable angina and/or congestive heart failure requiring hospitalization within
the last 3 months;
- History of recent myocardial infarction within 6 months prior to registration.
- Clinically significant interstitial lung disease
- Pregnancy: Administration of atezolizumab may have an adverse effect on pregnancy and
poses a risk to the human fetus, including embryo-lethality. 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
treatment, and for 5 months (150 days) after the last dose of study agent. 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
- Women who are breastfeeding and unwilling to discontinue
- History of allogeneic organ transplant
- Patients who have had immunotherapy-induced pneumonitis