A Phase II Trial of Atezolizumab + Carboplatin + Etoposide With Liver-Directed Radiotherapy (RT) in Extensive Stage Small Cell Lung Cancer (ES-SCLC) Patients With Liver Metastases
The purpose of this study is to evaluate whether radiation treatment directed at liver metastases can be safely added to standard of care treatment for extensive stage small cell lung cancer (ES-SCLC). The current standard treatment for people who have ES-SCLC is chemotherapy including drugs called carboplatin and etoposide, that is combined with a type of immunotherapy called atezolizumab. However, patients with liver involvement of their ES-SCLC don't respond as well to this treatment. The study aims to answer whether adding radiation directed at liver metastases can improve responses to standard chemo-immunotherapy in this patient population. All study participants will get the same study intervention, which will be chemo-immunotherapy and radiation therapy.
• Age≥ 18 years
• Histologically or cytologically confirmed ES-SCLC (per the Veterans Administration Lung Study Group (VALG) staging system)
• No prior treatment for ES-SCLC
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Patients with a history of treated, asymptomatic CNS metastases are eligible providing they meet the following criteria
‣ Only supratentorial and cerebellar metastases allowed (i.e., no metastases to midbrain, pons, medulla or spinal cord)
⁃ No ongoing requirement for corticosteroids as therapy for CNS disease
⁃ No stereotactic brain radiation within 7 days
⁃ No evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study
⁃ Patients with new asymptomatic Central Nervous System (CNS) metastases detected at the screening scan must receive radiation therapy and/or surgery for CNS metastases. Following treatment, these patients may then be eligible without the need for an additional brain scan prior to randomization, if all other criteria are met.
• At least one liver metastasis measuring 1 cm.
• Measurable disease, as defined by RECIST v1.1, in addition to the liver lesion(s) to which SBRT is planned.
• Patients must submit a pre-treatment tumor tissue sample from a liver metastasis. Tumor tissue must be obtained prior to the start of treatment.
• Adequate hematologic and end organ function, defined by the following laboratory results:
‣ Absolute neutrophil count (ANC) ≥1500 cells/μL without granulocyte colony-stimulating factor support
⁃ Lymphocyte count ≥500/μL
⁃ Platelet count ≥100,000/μL without transfusion
⁃ Hemoglobin ≥9.0 g/dL Patients may be transfused to meet this criterion.
⁃ International Normalized Ratio (INR) or Activated Partial Thromboplastin Time (aPTT) ≤1.5×upper limit of normal (ULN) This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose.
⁃ Aspartate aminotransferase (AST), Alanine Aminotransferase (ALT), and alkaline phosphatase ≤5×ULN
⁃ Serum bilirubin ≤1.25×ULN (Patients with known Gilbert disease who have serum bilirubin level ≤3×ULN may be enrolled)
⁃ Serum creatinine ≤1.5×ULN
⁃ For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods 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 6 months after the final dose of carboplatin and etoposide
‣ A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (≥12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). The definition of childbearing potential may be adapted for alignment with local guidelines or requirements.
‣ 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, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception
⁃ For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, as defined below:
∙ With female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom during treatment with chemotherapy (i.e., carboplatin and etoposide) and for at least 6 months after the last dose of chemotherapy to avoid exposing the embryo.
‣ 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 and withdrawal are not acceptable methods of contraception.
⁃ Negative HIV test at screening, with the following exception: patients with a positive HIV test at screening are eligible, provided they are stable on anti-retroviral therapy, have a CD4 count3 200/µL, and have an undetectable viral load
⁃ Ability to understand and the willingness to sign a written informed consent document.
⁃ Ability to comply with the study protocol, in the investigator's judgment.