This phase II trial studies the effect of lamivudine in combination with standard of care chemoimmunotherapy in treating patients with extensive stage small cell lung cancer. Even though small cell lung cancer is initially highly responsive to first-line chemotherapy treatment, treatment resistance inevitably emerges; treatment resistance is when tumor cells stop responding to a drug treatment that they had previously responded to. Lamivudine is an oral antiviral a drug that may be able to reduce the ability of tumors to develop drug resistance. Chemotherapy drugs, such as carboplatin and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. 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. Giving lamivudine together with the usual standard of care chemoimmunotherapy may help prevent the growth and spread of the tumor cells to other parts of the body.
PRIMARY OBJECTIVE: I. To evaluate the 6-month progression-free survival (PFS) rate of lamivudine in combination with platinum-based chemotherapy in patients with extensive stage small cell lung cancer (SCLC). SECONDARY OBJECTIVES: I. To evaluate the 12-month survival and overall survival (OS) of patients with extensive stage SCLC receiving study treatment. II. To assess the toxicity of the combination of lamivudine with platinum-based chemotherapy in this population. EXPLORATORY OBJECTIVE: I. To study tissue and blood-based biomarkers as potential predictors of treatment outcomes. OUTLINE: INDUCTION: Patients receive lamivudine orally (PO) once daily (QD) on days 1-28. Patients also receive carboplatin intravenously (IV) over 30-60 minutes and atezolizumab IV on day 1, and etoposide IV over 60-120 minutes on days 1-3. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive lamivudine PO QD on days 1-28 and atezolizumab IV on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. NOTE: Patients who are not eligible for atezolizumab as outlined in exclusion criteria or who refuse to receive atezolizumab may still be treated in this study with carboplatin and etoposide as the IV drug component, in addition to lamivudine orally administered. After completion of study treatment, patients are followed up for 30 days and then every 60 days thereafter.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
28
Roswell Park Cancer Institute
Buffalo, New York, United States
RECRUITINGProgression-free survival
The primary test of efficacy will be carried out using an exact binomial test of a proportion. Descriptive analyses will be carried out using the Kaplan-Meier product-limit estimator. Patients who are treated beyond RECIST progression and subsequently had tumor response while on study (and no other intervening treatment) will be classified as pseudoprogression and not counted as progression event.
Time frame: From the date of registration to the date of first confirmed progression or death, whichever occurred first, assessed at 6 months
Overall survival
Descriptive analyses will be carried out using the Kaplan-Meier product-limit estimator.
Time frame: From registration to death from any cause or 5 years from time of enrollment, whichever occurs first
Incidence of toxicities
Per National Cancer Institute Common Terminology Criteria for Adverse Events version 5, the term toxicity is defined as adverse events that are classified as either possibly, probably, or definitely related to study treatment. The maximum grade for each type of toxicity will be recorded for each patient and will be used for reporting. Frequency tables will be reviewed to determine toxicity patterns. In addition, all adverse event data graded as 3, 4, or 5 and classified as either "unrelated or unlikely to be related" to study treatment in the event of an actual relationship developing will be reviewed.
Time frame: Up to 30 days after the end of all treatment
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