Small cell lung cancer Cancer Malignant neoplasm of lung
Conditions
Interventions
Patients will be randomised to receive either olaparib or placebo 200 mg orally (per os [po]) twice a day (bis in die [bd]) for up to 2 years.
Sponsors
Sheffield Teaching Hospitals NHS Foundation Trust (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 23/01/2019: 1. Pathologically confirmed SCLC (limited or extensive stage) 2. Completed at least 3 cycles of first-line chemotherapy or chemo-radiotherapy with cisplatin + etoposide or carboplatin + etoposide 3. Complete Response (CR) or Partial Response (PR) to first-line chemotherapy (RECIST criteria) 4. ECOG performance status 0-2 5. Resolution of all treatment toxicity to grade 1 or better 6. Adequate physiological function: 6.1. Renal: 6.1.1. Calculated or measured creatinine clearance =50 ml/min 6.1.2. Serum creatinine =1.5 x institutional upper limit of normal (ULN) 6.2. Haematological: 6.2.1. Haemoglobin =9.0 g/dL 6.2.2. White blood cells (WBC) =3x109/L 6.2.3. Absolute Neutrophil Count (ANC) =1.5 x 109/L 6.2.4. Platelet count = 100 x 109/L 6.2.5. International Normalized Ratio (INR) =1.2 6.3. Hepatic: 6.3.1. Aspartate Aminotransferase (AST)/Alanine Aminotransferase (ALT) =2.5 x institutional ULN unless liver metastases are present in which case it must be =5x ULN 6.3.2. Bilirubin within normal range 7. Negative pregnancy test and agrees to comply with contraceptive measures 8. Provision of written informed consent 9. Able to swallow oral medication 10. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations Previous inclusion criteria: 1. Pathologically confirmed SCLC (limited or extensive stage) 2. Completed at least 3 cycles of first-line chemotherapy with cisplatin or carbopatin + etoposide 3. Complete Response (CR) or Partial Response (PR) to first-line chemotherapy (RECIST criteria) 4. ECOG performance status 0-2 5. Resolution of all treatment toxicity to grade 1 or better 6. Adequate physiological function: 6.1. Renal: 6.1.1. Calculated or measured creatinine clearance =50 ml/min 6.1.2. Serum creatinine =1.5 x institutional upper limit of normal (ULN) 6.2. Haematological: 6.2.1. Haemoglobin =9.0 g/dL 6.2.2. White blood cells (WBC) =3 x 10e9/L 6.2.3. Absolute Neutrophil Count (ANC) = 1.5 x 10e9/L 6.2.4. Platelet count =100 x 109/L 6.2.5. International Normalized Ratio (INR) =1.2 6.3. Hepatic: 6.3.1. Aspartate Aminoransferase (AST)/Alanine Aminotransferase (ALT) =2.5 x institutional ULN unless liver metastases are present in which case it must be =5x ULN 6.3.2. Bilirubin within normal range 7. Negative pregnancy test and agrees to comply with contraceptive measures 8. Provision of written informed consent 9. Able to swallow oral medication 10. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 23/01/2019: 1. Age =18 years 2. Interval from last anticancer treatment to the start of the study treatment: 2.1. Radiotherapy =21 days 2.2. Chemotherapy =42 days 3. Symptomatic brain metastases 4. Interstitial lung disease 5. Previous malignancies (except curatively treated non-melanoma skin cancer or carcinoma in situ of the cervix or breast) within the past 3 years 6. History of malabsorption or major gastrointestinal tract resection likely to affect study drug absorption. 7. Treatment with any investigational product during the last 14 days (or a longer period depending on the defined characteristics of the agents used) 8. Any previous treatment with a PARP inhibitor, including olaparib 9. Patients receiving the following classes of inhibitors of CYP3A4; azole antifungals; macrolide antibiotics; protease inhibitors 10. Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent. 11. Breastfeeding women 12. Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV) 13. Patients with known active hepatic disease (i.e., Hepatitis B or C) 14. Patients with a known hypersensitivity to Olaparib or any of the excipients of the product 15. Patients with uncontrolled seizures 16. Patients with myelodysplastic syndrome (MDS) / acute myeloid leukaemia (AML) 17. Major surgery within 14 days of starting trial treatment and patients must have recovered from any effects of any major surgery Previous exclusion criteria: 1. Age =18 years 2. Interval from last anticancer treatment to the start of the study treatment: 2.1. Radiotherapy =21 days 2.2. Chemotherapy =42 days 3. Symptomatic brain metastases 4. Active infection on the day of enrollment 5. Interstitial lung disease 6. Previous malignancies (except curatively treated non-melanoma skin cancer or carcinoma in situ of the cervix or breast) within the past 3 years 7. History of malabsorption or major gastrointestinal tract resection likely to affect study drug absorption. 8. Treatment with any investigational product during the last 14 days (or a longer period depending on the defined characteristics of the agents used) 9. Any previous treatment with a PARP inhibitor, including olaparib 10. Patients receiving the following classes of inhibitors of CYP3A4; azole antifungals; macrolide antibiotics; protease inhibitors 11. Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining informed consent. 12. Breastfeeding women 13. Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV) 14. Patients with known active hepatic disease (i.e., Hepatitis B or C) 15. Patients with a known h
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome as of 23/01/2019: Progression-free survival time Previous primary outcome: Progression-free survival rate at 4 months from randomisation | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcomes as of 23/01/2019: 1. Progression-free survival rate at 4 months from randomisation 2. Overall survival time 3. Overall survival rate at 6 months 4. Changes in performance status 5. Quality of life 6. Adverse events 7. Biomarkers: blood and biopsy samples will be collected for analysis of PARP and DNA repair pathways Previous secondary outcomes: 1. Progression-free survival time 2. Overall survival time 3. Overall survival rate at 6 months 4. Changes in performance status 5. Quality of life 6. Adverse events 7. Biomarkers: blood and biopsy samples will be collected for analysis of PARP and DNA repair pathways | — |
Countries
England, United Kingdom
Outcome results
None listed