Clinical Trials /

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

NCT02679963

Description:

This is a multicentre randomised double-blind phase II trial, sponsored by Gustave Roussy and involving one French center as well as the Spanish Lung Cancer Group (≈20 centers of the SLCG). Six hundred patients with diagnosis of stage IIIB/IV NSCLC will initially be registered prior to receiving the first line platinum-based chemotherapy or during or at the end of the first 6 cycles of inducation platinium based chemotherapy and provide consent for retrieving archival tissue collection and providing translational blood samples and tumor biopsies. 1. - Induction chemotherapy phase All patients will initially be treated with 6 cycles of platinum-based induction chemotherapy. Cycle duration will be 21 days. Doublets should either consist of a pemetrexed-platinum (cisplatin or carboplatin) doublet (preferentially for non-squamous NSCLC) or a gemcitabine - or vinorelbine - platinum doublet for squamous NSCLC. Taxanes-platinum doublets will not be accepted. Translational blood samples will be taken at the beginning of induction chemotherapy for all patients. Patients displaying progressive disease or stable disease after induction chemotherapy will be withdrawn and further optimally managed according to local practice. For them, an optional tumour biopsy will be performed at the end of the induction treatment. 2. - Randomisation and maintenance phase Only patients who respond to platinum-based induction chemotherapy will be further randomised between olaparib and placebo. These patients must have been treated with 6 cycles of chemotherapy. However, patients who haven't received 6 cycles of the induction chemotherapy due to severe toxicity (grade 3 or 4, NCI CTCAE v4.0) could be randomized only if they had received 4 chemotherapy cycles at least and if all treatment related toxicities are resolved to a grade ≤ 1 (NCI CTCAE v4.0). Treatment will be administered at a dose of 600 mg daily (2 doses of 300 mg [2 tablets of 150 mg] taken approximately 12 hours apart) and cycle duration will be 28 days. Disease will be assessed every 2 cycles by CTscan (MRI or PET-scan if the scan is not contributive) and treatment will be administered until disease progression or unacceptable toxicity. Patients will then be optimally managed according to local practice. Follow-up will be for a minimum of 15 months from the time of randomization, and until last venue. All randomised patients will be asked to provide translational blood samples at randomization, on treatment and at the end of the treatment. Optional tumour biopsies will be performed at randomization, at the end of the treatment (or at disease progression if available).

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Trial Evaluating Maintenance Olaparib in Patients With Platinum-sensitive Advanced Non-small Cell Lung Cancer
  • Official Title: A Randomized Double-blind Phase II Trial Evaluating Maintenance Olaparib Versus Placebo in Patients With Platinum-sensitive Advanced Non-small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: 2014-005586-75
  • SECONDARY ID: 2014/2204
  • NCT ID: NCT02679963

Conditions

  • Non Small Cell Lung Cancer

Interventions

DrugSynonymsArms
OlaparibMaintenance Olaparib
PlaceboPlacebo

Purpose

This is a multicentre randomised double-blind phase II trial, sponsored by Gustave Roussy and involving one French center as well as the Spanish Lung Cancer Group (≈20 centers of the SLCG). Six hundred patients with diagnosis of stage IIIB/IV NSCLC will initially be registered prior to receiving the first line platinum-based chemotherapy or during or at the end of the first 6 cycles of inducation platinium based chemotherapy and provide consent for retrieving archival tissue collection and providing translational blood samples and tumor biopsies. 1. - Induction chemotherapy phase All patients will initially be treated with 6 cycles of platinum-based induction chemotherapy. Cycle duration will be 21 days. Doublets should either consist of a pemetrexed-platinum (cisplatin or carboplatin) doublet (preferentially for non-squamous NSCLC) or a gemcitabine - or vinorelbine - platinum doublet for squamous NSCLC. Taxanes-platinum doublets will not be accepted. Translational blood samples will be taken at the beginning of induction chemotherapy for all patients. Patients displaying progressive disease or stable disease after induction chemotherapy will be withdrawn and further optimally managed according to local practice. For them, an optional tumour biopsy will be performed at the end of the induction treatment. 2. - Randomisation and maintenance phase Only patients who respond to platinum-based induction chemotherapy will be further randomised between olaparib and placebo. These patients must have been treated with 6 cycles of chemotherapy. However, patients who haven't received 6 cycles of the induction chemotherapy due to severe toxicity (grade 3 or 4, NCI CTCAE v4.0) could be randomized only if they had received 4 chemotherapy cycles at least and if all treatment related toxicities are resolved to a grade ≤ 1 (NCI CTCAE v4.0). Treatment will be administered at a dose of 600 mg daily (2 doses of 300 mg [2 tablets of 150 mg] taken approximately 12 hours apart) and cycle duration will be 28 days. Disease will be assessed every 2 cycles by CTscan (MRI or PET-scan if the scan is not contributive) and treatment will be administered until disease progression or unacceptable toxicity. Patients will then be optimally managed according to local practice. Follow-up will be for a minimum of 15 months from the time of randomization, and until last venue. All randomised patients will be asked to provide translational blood samples at randomization, on treatment and at the end of the treatment. Optional tumour biopsies will be performed at randomization, at the end of the treatment (or at disease progression if available).

Trial Arms

NameTypeDescriptionInterventions
Maintenance OlaparibExperimentalOlaparib (experimental arm): 600 mg daily (2 doses of 300 mg (2*2 tablets of 150 mg) taken approximately 12 hours apart) po, administered until disease progression or toxicity requiring its interruption. Olaparib has to be started no later than 6 weeks after the last administration of induction chemotherapy, and no later than 3 weeks after the CT scan confirming response to induction chemotherapy
  • Olaparib
PlaceboPlacebo ComparatorPlacebo (control arm): 2 doses of 300 mg per day (2*2 tablets of 150 mg) taken approximately 12 hours apart
  • Placebo

Eligibility Criteria

        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).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival
Time Frame:Assessed every 56 days up to 15 months
Safety Issue:
Description:By CT scan, MRI or TEP-scan according to RECIST 1.1 criteria

Secondary Outcome Measures

Measure:Overall Survival
Time Frame:Measured from patient randomization to death or last follow-up for patient alive or consent withdrawal up to 15 months
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Gustave Roussy, Cancer Campus, Grand Paris

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