lung cancer
Conditions
Interventions
Patients will receive standard of care: radiotherapy alone (1), sequential
chemoradiotherapy (2) or concurrent chemoradiotherapy (3). In addition patients
will receive the experimental treatment wit
Sponsors
Antoni van Leeuwenhoek Ziekenhuis
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. >=18 years of age 2. Histologically or cytologically confirmed diagnosis of NSCLC 3. For chemoradiotherapy patients only: stage II/III non-operable disease, without malignant pleural effusion 4. For (sequential chemo-)radiotherapy patients only: indication for radical locoregional radiotherapie 5. Acceptable pulmonary function as defined by a Fev1 of >=30% and a DLCO of >= 40% of predicted, 6. NYHA I-II functional status 7. Expected risk of radiation-induced pulmonary toxicity is modest: MLD = 6.2 mmol/l b. Leucocytes > 3.0 x 109/l c. Absolute neutrophil count > 1.5x109/l d. Platelet count > 100 x 109/l e. Total bilirubin = 70 ml/min; creatinine clearance >= 50 ml/min in patients not receiving concurrent cisplatin; measured using a 24-hours urine sample or calculated using the Cockcroft-Gault formula i. Urine dipstick for proteinuria = 2, 24 hour urine must demonstrate = 2 (CTCAE) 12. Patients of reproductive potential must agree to practice two effective medically approved contraceptive method during the trial and 3 months afterwards 13. Signed written informed consent.
Exclusion criteria
Exclusion criteria: 1. Concurrent active malignancy other than localized, non-melanoma skin cancer or carcinoma-in-situ of the cervix (unless definitive treatment was completed 1 year or more before study entry and the patient has remained disease free) 2. Anti-cancer therapy including chemotherapy, radiotherapy, endocrine therapy, immunotherapy or use of other investigational agents within the 3 weeks prior to start of therapy (or a longer period depending on the defined characteristics of the agents used e.g. 6 weeks for mitomycin or nitrosourea). Patients may continue the use of LHRH agonists for cancer; bisphosphonates for bone disease and corticosteroids. 3. Patients, selected for sequential chemoradiotherapy, are excluded if no disease control (all responses except progression) is obtained after induction chemotherapy. 4. Prior: o Ipsilateral radiotherapy to the chest; o Chemotherapy within the last year 5. History of interstitial pneumonitis (to include diffuse alveolar damage, non-malignant causes of pneumonitis, ARDS, alveolitis, cryptogenic organising pneumonia, obliterative bronchiolitis, non-malignant causes of pulmonary fibrosis, eligibility based on the judgement of the primary investigator), active infection on day of enrollment 6. Significant cardiovascular disease as defined by: o History of congestive heart failure requiring therapy; o History of unstable angina pectoris or myocardial infarction up to 6 months prior to trial entry; o Presence of severe valvular heart disease; o Presence of a ventricular arrhythmia requiring treatment; o Uncontrolled hypertension 7. Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be assessed with the patient before registration in the trial. 8. Participation in other trial with investigational drug or treatment modality 9. Co-existing serious active infection requiring parenteral antibiotics 10. Patients with hepatic disease e.g. patients with known serologically positive Hepatitis B or Hepatitis C as they may be more at risk of toxicity from Olaparib 11. Immunocompromised patients e.g. human immunodeficiency virus (HIV) 12. Myelodysplastic syndrome/acute myeloid leukaemia or features suggestive of MDS/AML on peripheral blood smear 13. Any co-existing medical condition that in the investigator*s judgement will substantially increase the risk associated with the patient*s participation in the study 14. Gastrointestinal disorders that may interfere with absorption of the study drug or patients who are not able to take oral medication 15. Concomitant medications: a. Any previous treatment with a PARP inhibitor, including Olaparib b. Patients receiving the following classes of inhibitors of CYP3A4 (see Section 7.4 for guidelines and wash out periods) - Azole antifungals - Macrolide antibiotics - Protease inhibitors 16. Persistent grade 2 or greater toxicities, from any cause 17. Pregnant or breast-feeding women
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The incidence of dose limiting toxicities (DLTs) including severe late esophageal toxicity (sLET). | — |
Secondary
| Measure | Time frame |
|---|---|
| o Additional safety variables: (S)AE*s, Laboratory parameters, Vital signs, Lung function, Long term toxicity (toxicity related to treatment, occurring or persisting from 3 months after the last irradiation day until 5 years after treatment) o PK variables (AUC, Cmax, Cmin) o Pd variables (PARP inhibition; γH2AXfoci formation) o Objective tumor response o Surrogate biomarkers for antitumor response: metabolic response determined by FDG-PET/CT-imaging), change in circulating tumor cells, molecular/biological parameters (tumor markers) o Locoregional control rate (LRCR) at one year o Localisation of recurrences with respect to different dose levels administered (inside or outside Planning Target Volume) o Progression free survival | — |
Countries
Netherlands
Outcome results
None listed