Trial Evaluating Maintenance Olaparib in Patients With Platinum-sensitive Advanced Non-small Cell Lung Cancer (PIPSeN)

This is an interventional treatment trial for Non Small Cell Lung Cancer Read More

For inclusion in the study subjects should fulfill the following criteria:

1. Provision of written informed consent to treatment and companion translational studies prior to any study specific procedures
2. Patients must be > 18 years of age.
3. Affiliation to an health insurance
4. Histological diagnosis of NSCLC
5. Advanced or metastatic disease (stage IIIB/IV)
6. Access to the original tumor biopsy or planning of a fresh tumor biopsy before start the platinium based chemotherapy
7. Chemonaive for NSCLC or patient having received adjuvant chemotherapy at least 2 years before trial enrolment or patient currently receiving his/her first platinum-based chemotherapy for advanced NSCLC (first line or second line only if the first line was an anti-PD-1 or anti-PD-L1 agent monotherapy)
8. No other cancer in the previous 3 years, except cervical cancer or cutaneous cancer
9. Absence of EGFR-sensitising mutation or ALK translocation
10. ECOG Performance Status of 0-1
11. Fit to receive 6 cycles or currently receiving of platinum-based induction chemotherapy

12. At the start of the platinium based induction chemotherapy measurable lesions by RECIST v1.1 criteria, i.e. at least one lesion, not previously irradiated, that can be accurately measured at baseline as ≥ 10mm in the longest diameter (except lymph nodes that must have short axis ≥ 15mm) with computed tomography (CT), magnetic resonance imaging (MRI) or clinical examination and which is suitable for accurate repeated measurements.

    Inclusion criteria 13 is only for patients registered before starting the platinum-based induction chemotherapy:

13. Patients must have normal organ and bone marrow function measured within 14 days prior to administration of the platinum based treatment

    • Haemoglobin ≥ 10.0 g/dL
    • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
    • Platelet count ≥ 100 x 109/L
    • Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
    • 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 > 60mL/min as calculated by Cockroft-Gault formula for cisplatin administration; creatinine clearance >/= 51mL/min by Cockroft-Gault formula for carboplatin administration

14. Evidence of non-childbearing status for women of childbearing potential: negative serum pregnancy test within 14 days of study treatment.

    Postmenopausal is defined as:

    • Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments,
    • LH and FSH levels in the post-menopausal range for women under 50,
    • Radiation-induced oophorectomy with last menses >1 year ago,
    • Chemotherapy-induced menopause with >1 year interval since last menses,
    • Or surgical sterilisation (bilateral oophorectomy or hysterectomy).
15. Both men and women (of childbearing potential) who are sexually active should accept to use adequate contraception, during and for at least 6 months post-treatment
16. 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.
17. Previous surgery (in the adjuvant setting) for NSCLC, radiotherapy (with a curative intent for local or locally-advanced disease) or immunotherapy by anti- PD-1 or anti-PD-L1 agent in the metastatic setting are allowed

Non-inclusion criteria:

1. Uncontrolled or symptomatic brain metastases. Controlled brain metastases are defined as stable for 1 month. A scan to confirm the absence of brain metastases is not required. Corticosteroids therapy will be allowed if administered at a stable dose for at least one month before entering the trial.
2. Previous enrolment (or randomisation) in the present study Any previous systemic treatment for cancer in the previous 3 years.
3. Any previous systemic treatment for cancer in the previous 3 years except for NSCLC.
4. Patients receiving any radiotherapy or considering to require radiotherapy to the lung at the time of study entry or in the near future, except for palliative reasons. The patient can receive a stable dose of bisphosphonates for bone metastases, before and during the study as long as these were started at least 4 weeks prior to inclusion.

5. Patients receiving the following classes of inhibitors of CYP3A4 (see Section 6.5 for guidelines and wash out periods).

   • Azole antifungals
   • Macrolide antibiotics
   • Protease inhibitors
6. Major surgery within 14 days before to start the induction chemotherapy and patients who have not recovered from any effects of any major surgery.
7. 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, coronary artery disease, cardiomyopathy, uncontrolled hypertension, myocardial infarction in the last 3 months, unstable spinal cord compression (untreated and unstable for at least 28 days prior to start the induction chemotherapy), superior vena cava syndrome, extensive bilateral lung disease on HRCT scan or any psychiatric disorder that prohibits obtaining informed consent.
8. Pregnant and/or breast-feeding women.
9. Patients who are known to be serologically positive for human immunodeficiency virus (HIV) and/or are receiving antiviral therapy. Systematic serologies to confirm the absence of this disease are not required.
10. Patients with known active hepatic disease (i.e., Hepatitis B or C) Systematic serologies to confirm the absence of these diseases are not required.
11. Patients with a known hypersensitivity to olaparib/placebo, cisplatin, carboplatin, or other platinum containing compounds, or any of the excipients of the product.
12. Concomitant yellow fever vaccine
13. Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of olaparib/placebo.
14. Symptomatic peripheral neuropathy ≥ grade 2
15. Patients with uncontrolled seizures
16. Patients with myelodysplastic syndrome/acute myeloid leukaemia.
17. Enrolment in another clinical trial (except observational study).