None listed
Conditions
Brief summary
This trial aims to determine the safety, feasibility, and efficacy of a combination of chemotherapy, immunotherapy, and chest radiation therapy in extensive stage small cell lung cancer. Who is it for? You may be eligible for this study if you are 18 or above and have untreated extensive stage small cell lung cancer. Study details Participants will be given durvalumab (an immunotherapy drug) concurrently with 4 cycles of cisplatin/carboplatin and etoposide chemotherapy, which is given as in injection every three weeks over approx. 12 weeks. Maintenance treatment with durvalumab alone will continue every 4 weeks after the completion of the chemotherapy cycles until there is evidence of disease progression. Participants will also receive 10 chest radiotherapy sessions, which will take approx. 2 weeks to complete (given either concurrently with cycle 3 or 4 of chemotherapy (called concurrent radiotherapy) or within 6 weeks of finishing chemotherapy (called consolidation radiotherapy). Fractions are expected to be delivered daily. When RT is to start depends on the location and size of the area to be treated). Throughout the study, participants will be monitored regularly for any adverse effects, and for progression of disease using a number of imaging techniques. It is hoped that this study may demonstrate that chest radiation is safe and beneficial when given in combination with chemotherapy and immunotherapy for the treatment of extensive stage small cell lung cancer.
Interventions
Radiation: Thoracic Radiotherapy
Participants will receive thoracic radiotherapy to a dose of 30 Gray (Gy) in 10 fractions (3 Gy per day) concurrently with cycle 3 or 4 of chemo-immunotherapy (Group 1).
Participants who are unsuitable for concurrent radiotherapy may receive consolidation radiotherapy. Consolidation thoracic radiotherapy will be administered to a dose of 30 Gy in 10 fractions, following 4 cycles of chemo-immunotherapy (Group 2).
Treatment fractions will be delivered daily, where
Radiation: Thoracic Radiotherapy Participants will receive thoracic radiotherapy to a dose of 30 Gray (Gy) in 10 fractions (3 Gy per day) concurrently with cycle 3 or 4 of chemo-immunotherapy (Group 1). Participants who are unsuitable for concurrent radiotherapy may receive consolidation radiotherapy. Consolidation thoracic radiotherapy will be administered to a dose of 30 Gy in 10 fractions, following 4 cycles of chemo-immunotherapy (Group 2). Treatment fractions will be delivered daily, where treatment should be completed within 15 days (9-10 fractions a fortnight). Drug: Etoposide with Carboplatin or Cisplatin (Chemotherapy) The chemotherapy in this study is a standard treatment for extensive-stage small-cell lung cancer (EC-SCLC). The combination of chemotherapy (etoposide + carboplatin or etoposide + cisplatin) which the participant will receive is dependent on what is standard at the treatment centre. Chemotherapy will be administered via an intravenous infusion every 3 weeks (21 days) for 4 cycles. Drug: Durvalumab (Immunotherapy) The immunotherapy in this study is a standard treatment for ES-SCLC. Participants will receive a dose of 1500 mg of Durvalumab via an intravenous infusion every 3 weeks (21 days) for 4 cycles, concurrently with chemotherapy. A 1500 mg maintenance dose of Durvalumab will be administered every 4 weeks after completion of chemotherapy (monotherapy).
Sponsors
Trans Tasman Radiation Oncology Group
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
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; a. asymptomatic without steroid therapy may be included or b. 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 greater than or equal to 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; a. are willing to use adequate contraceptive measures until 90 days after the final dose of trial treatment b. are not breast feeding c. 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: a. Concurrent chemotherapy (not relevant to patients registered prior to cycle 2who 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 b. An investigational product during the last 4 weeks c. 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 d. Immunosuppressive medication within 14 days before the first dose of Durvalumab. Some exceptions apply e. Live, attenuated vaccine within 30 days prior to the first dose of Durvalumab f. 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
Outcome results
None listed