Chemotherapy and Immunotherapy in Extensive-Stage Small-Cell Lung Cancer With Thoracic Radiotherapy

This is a prospective, multi-centre, single arm, phase 2, open label clinical trial of patients with untreated extensive-stage small-cell lung cancer (ES-SCLC) suitable for first-line platinum-based chemotherapy. The aim of the trial is to assess safety, feasibility and describe efficacy of the addition of concurrent thoracic radiotherapy to usual treatment of chemotherapy and immunotherapy (durvalumab) in patients with ES-SCLC.


Eligibility Criteria:
Inclusion Criteria:

* Provided written informed consent
* Histologically or cytologically documented ES-ECLC
* Thoracic disease deemed suitable for radiation therapy following initial systemic therapy
* If brain metastases present, then they are to be;

  1. asymptomatic without steroid therapy may be included or
  2. have required treatment (radiotherapy and/or surgery) and are clinically stable and patient is on a stable or reducing steroid dose of no more than dexamethasone 4mg/day (or equivalent)
* Patients must be considered suitable to receive platinum-based chemotherapy regimen as first-line treatment for ES-SCLC
* ECOG performance-status score of 0 or 1 at registration
* Life expectancy ≥ 12 weeks at registration
* Body weight \> 30 kg
* No prior exposure to immune-mediated therapy including, but not limited to, other anti-cytotoxic T-lymphocyte-associated antigen-4, anti-programmed cell death-1, anti-programmed cell death ligand-1, and anti-programmed cell death ligand-2 antibodies, excluding therapeutic anticancer vaccines
* Adequate organ and marrow function as defined in the Protocol
* Female patients who;

  1. are willing to use adequate contraceptive measures until 90 days after the final dose of trial treatment
  2. are not breast feeding
  3. have a negative pregnancy test prior at registration if of child bearing potential or have evidence of non-child bearing potential by fulfilling the criteria as stated in the Protocol at screening

Exclusion Criteria:

* Treatment with any of the following:

  1. Concurrent chemotherapy (not relevant to patients registered prior to cycle 2 who will have received a cycle of platinum/etoposide chemotherapy), investigational product, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable
  2. An investigational product during the last 4 weeks
  3. High dose radiotherapy to the chest prior to systemic therapy precluding further thoracic radiation therapy. Radiation therapy outside of the chest for palliative care (i.e., bone metastasis) is allowed but must be completed before first dose of the trial medication
  4. Immunosuppressive medication within 14 days before the first dose of durvalumab. Some exceptions apply
  5. Live, attenuated vaccine within 30 days prior to the first dose of durvalumab
  6. Major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of Durvalumab. Surgical procedures to obtain a lung cancer diagnosis or for palliation are allowed
* Medical contraindication to, known allergy or hypersensitivity to durvalumab, etoposide, carboplatin (patients with allergy/hypersensitivity to carboplatin may receive cisplatin), cisplatin, or any of their excipients
* History of allogeneic organ transplantation
* Has a para-neoplastic syndrome (PNS) of autoimmune nature, requiring systemic treatment (systemic steroids or immunosuppressive agents) or has a clinical symptomatology suggesting worsening of PNS. Patients with hyponatraemia considered due to SIADH syndrome are eligible
* Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis. Some exceptions apply
* Interstitial lung disease/pulmonary fibrosis. Patients with emphysema and associated limited areas of pulmonary fibrosis are eligible
* Uncontrolled intercurrent illness
* History of another primary malignancy. Some exceptions apply
* History of leptomeningeal carcinomatosis
* History of active primary immunodeficiency
* Patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab