NRG-LU007 - RAndomized Phase 2/3 Trial Of Consolidation Radiation + Immunotherapy for ES-SCLC: RAPTOR trial

This study is being done to answer the following question: Can we extend the time without your extensive small cell lung cancer growing or spreading by adding radiation therapy to the usual treatment for this type of cancer (an immunotherapy drug called atezolizumab)? We are doing this study because we want to find out if this approach is better or worse than the usual approach for your type of cancer. The usual approach is defined as care most people get for extensive stage small cell lung cancer.

8081 Innovation Park Drive

Fairfax, VA 22031

• 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. Patients must be randomized within 9 weeks of last dose of etoposide/platinum (if not receiving PCI) or 6 weeks from completion of 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 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.
• Age ≥ 18
• ECOG Performance Status of 0-2
• 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.

• Metastatic disease invading the liver (>3 metastases), heart or >10 metastatic sites detectable after induction systemic therapy.
• 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. 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 are eligible.
    • Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA. 
  • Known immunosuppressive disease, for example history of bone marrow transplant or CLL;
  • Chronic obstructive pulmonary disease (COPD) requiring chronic oral steroid therapy of > 10 mg prednisone daily or equivalent. 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.
• History of allogeneic organ transplant.
• Patients who have had immunotherapy-induced pneumonitis.