(TESSERACT): Phase I/II Trial in ES-SCLC to Enhance Response to Atezolizumab Plus Chemotherapy With Total Body Irradiation (TBI)
This phase I/II trial studies the side effects, safety, and effectiveness of low dose radiation to the entire body (total body irradiation \[TBI\]) and higher dose radiation to known areas of cancer (hypofractionated radiation therapy \[H-RT\]) combined with atezolizumab and chemotherapy (carboplatin \& etoposide) in treating patients with small cell lung cancer that has spread to disease sites outside of the lung (extensive stage). Extensive stage disease has historically been treated with chemotherapy alone with consideration of chest (thoracic) radiation therapy for those with response to chemotherapy, as well as consideration of preventative radiation therapy to the head (prophylactic cranial irradiation). Emerging evidence supports the synergistic interactions between immunotherapy and radiation therapy. 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. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair and may kill tumor cells. Combining TBI and H-RT with atezolizumab and chemotherapy may improve response to treatment.
• Age ≥ 18 years at time of informed consent
• Histologically documented or cytologically confirmed diagnosis of extensive stage small-celllung cancer with evaluable disease per RECIST v1.1 criteria. Patients may be considered extensive-stage based on M1 disease per AJCC 8th edition, OR may be clinically staged as extensive-stage disease based on anatomical extent that would preclude the use of standard radiotherapy fields as assessed by the treating radiation oncologist.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L
• Platelet count ≥ 100 x 10\^9/L
• Lymphocyte count ≥ 0.5 x 10\^9/L
• Hemoglobin ≥ 9 g/dL
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) ≤ 2.5 x ULN, alanine aminotransferase (ALT) ≤ 2.5 x ULN and alkaline phosphatase ≤ 2.5 x ULN
• Creatinine ≤ 1.5 x ULN or calculated creatinine clearance (CrCl) ≥ 50 mL/min if creatinine (Cr) \> 1.5 x ULN. GFR can also be utilized. If no local calculation guidance on CrCl, should be calculated according to Cockcroft-Gault Method
• International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 x ULN and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless participant is receiving anticoagulation therapy. For patients receiving therapeutic anticoagulation: stable anticoagulant regimen.
• Negative HIV test at screening, with the following exception: patients with positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy, have a CD4 count ≥ 200, and have an undetectable viral load
• Negative Hepatitis B surface antigen at screening
• Presence of brain metastases allowed (should undergo management with surgery and/or radiation therapy if symptomatic prior to TESSERACT radiation regimen; upfront cranial irradiation not mandatory on protocol if asymptomatic)
• Contraceptive use should be initiated or continued per guidance in labeling for approved chemotherapies
• Female patients must be non-pregnant and not breastfeeding
• Women of childbearing potential (WOCBP) 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. A woman is considered to be of childbearing potential if she is post-menarchal, has not reached a post-menopausal state (12 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, symptomthermal or postovulation methods) and withdrawal are not adequate methods of contraception.
⁃ With a female partner of childbearing potential who is not pregnant, men who are not surgically sterile must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of \< 1% per year during the treatment period and for 5 months after the final dose of atezolizumab. Men must refrain from donating sperm during this same period.
⁃ With a pregnant female partner, men must remain abstinent or use a condom during the treatment period and for 5 months after the final dose of atezolizumab 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 (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal.
• Eligible for immunotherapy-based systemic regimens per judgment of patient's study physician
• Able to submit written informed consent