non-small-cell lung cancer (NSCLC) MedDRA version: 21.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Olaparib
Product Code: [D0810000000]
Pharmaceutical Form: Tablet
Current Sponsor code: Olaparib
Other descriptive name: Olaparib
Concentration unit: mg milligram(s)
Concentration type: e
Sponsors
FONDAZIONE RICERCA TRASLAZIONALE (FORT)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria: 1. Body weight >30kg 2. Recurrent or metastatic NSCLC relapsed during or after completion of chemoradiotherapy with curative intent and maintenance durvalumab for stage III disease. Patients are eligible if they receive at least two cycles of platinum based chemotherapy or radical radiotherapy 3. Tumor tissue available for biomarker testing. 4. Evidence of disease progression during durvalumab maintenance or at the end of planned treatment. Patients who have interrupted planned durvalumab treatment after at least 6 months for reasons other than toxicity or progression (e.g. patient’s choice, logistic reasons, intercurrent acute illnesses) are eligible. Patients progressing during the first three months of Durvalumab are not eligible 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 6. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up 7. Age >18 years at time of study entry 8. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations. 9. Life expectancy of at least 16 weeks 10. Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:: ¿ Haemoglobin =10.0 g/dL with no blood transfusion in the past 28 days ¿ Absolute neutrophil count (ANC) =1.5 × 109 /L ¿ Platelet count =100 × 109/L ¿ Serum bilirubin =1.5 x institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician. ¿ AST (SGOT)/ALT (SGPT) =2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be =5x ULN ¿ creatinine clearance estimated of =51 mL/min using the Cockcroft-Gault equation or based on a 24 hour urine test: Males: Creatinine CL (mL/min) = Weight (kg) x (140 – Age) 72 x serum creatinine (mg/dL) Females: Creatinine CL (mL/min) = Weight (kg) x (140 – Age) x 0.85 72 x serum creatinine (mg/dL) 11. Female patients should be using adequate contraceptive measures (highly effective method of contraception are present in table 3 of protocol “Highly Effective Methods of Contraception (<1% Failure Rate)”), should not be breastfeeding, from the time of screening throughout the total duration of the drug treatment and the drug washout period (90 days after the last dose of durvalumab monotherapy) or for at least 1 month after last dose of olaparib, or they must totally/truly abstain from any form of sexual intercourse. Females of childbearing potential are defined as those who are not surgically sterile (ie, bilateral salpingectomy, bilateral oophorectomy, or complete hysterectomy) or post-menopausal. 12. Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1. 13. Male patients must use a condo
Exclusion criteria
Exclusion criteria: 1. No evidence of disease progression 2. Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment 3. Patients not pretreated with durvalumab with curative intent 4. Patients treated with non-radical radiotherapy or with non conventional radiotherapy 5. More than 4 cycles of platinum-based chemotherapy 6. Rapid progressors. Progressors within first 3 month of treatment will be excluded from this trial 7. Any clinical reason that makes the patient ineligible to receive any investigator’s choice single-agent chemotherapy regimen (for patients enrolled in cohorts A and B) 8. Any clinical reason that makes the patient ineligible to receive any investigator’s choice platinum-based doublet chemotherapy regimen (for patients enrolled in cohorts C and D) 9. Persistent toxicities (>Common Terminology Criteria for Adverse Event (CTCAE) grade 2) caused by previous cancer therapy, excluding alopecia. 10. Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MDS/AML. 11. Disease progression within the first three months of Durvalumab therapy 12. Tumor tissue not available 13. Evidence of EGFR mutations or ALK or ROS1 rearrangements 14. Performance status >1 (ECOG) 15. Brain metastases are allowed if asymptomatic and pretreated. 16. Diagnosis of another cancer in the last 3 years, except for in situ carcinoma of cervix, breast and bladder or skin carcinoma ( 17. Patient with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days prior to enrolment.. 18. Leptomeningeal disease. 19. Resting ECG indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (, or patients with congenital long QT syndrome. 20. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Patients with indwelling catheters (e.g., PleurX) are allowed. 21. Malignancies other than NSCLC within 5 years prior to enrollment, with the exception of those with a negligible risk of metastasis or death (e.g., expected 5-year OS> 90%) treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent, grade 1 endometrial carcinoma) 22. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins and patient with a known hypersensitivity to olaparib or any of the excipient of the product. 23. Known hypersensitivity or allergy to any component of the Durvalumab formulation 24. History of autoimmune disease 25. Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. 26. Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication. 27. History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted. 28. Positive test for
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The co-primary objectives of the study are as follows: 1) to investigate whether durvalumab prolongs survival when added to single agent chemotherapy (arm A) versus single agent chemotherapy (arm B) in patients progressing during durvalumab given as maintenance therapy in stage III disease; 2) whether, after chemoimmunotherapy, the addition of olaparib to durvalumab (arm C) improves survival over durvalumab (arm D) in patients relapsing after completing durvalumab maintenance therapy for stage III disease.;Secondary Objective: NA;Primary end point(s): Primary Endpoint: Overall survival (OS) in arm A versus B and in arm C versus D;Timepoint(s) of evaluation of this end point: Secondary Endpoint(s): The secondary endpoints are as follows: •Progression-free survival (PFS) in arm A versus B and in arm C versus D; •objective response rate (ORR) in arm A versus B and in arm C versus D; •safety and incidence of AEs in each arm according to treatment; •PFS and overall survival (OS) according to biomarkers (i.e., PD-L1, ERCC1, SLFN11, STK11, KEAP1, p53 expression, DNA repair genes [including BRCA 1-2 mutations] and tumor mutational burden). | — |
Countries
Italy
Contacts
Public ContactClinical Operations
Clinical Research Technology
Outcome results
None listed