A study to evaluate the potential benefit of the addition of buparlisib to standard therapy (carboplatin and paclitaxel) in the treatment of lung cancer

Phase 1

Conditions: squamous non small cell lung cancer
MedDRA version: 14.1Level: PTClassification code 10029522Term: Non-small cell lung cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.1Level: PTClassification code 10029521Term: Non-small cell lung cancer stage IIIBSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.1Level: PTClassification code 10059515Term: Non-small cell lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.1Level: PTClassification code 10001254Term: Adenosquamous cell lung cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.1Level: LLTClassification code 10001253Term: Adenosquamous cell lung cancer stage IIIBSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2012-005541-21-FR

Lead Sponsor: ovartis Pharma Services AG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 220

Inclusion Criteria

-Patient has histologically and/or cytologically confirmed diagnosis of squamous NSCLC. Diagnosis of mixed squamous and non-squamous or adenosquamous NSCLC will be acceptable for enrollment.
- Patient has archival or fresh tumor tissue for the exploratory
analysis of biomarkers related to sensitivity to PI3K
inhibitors.
- Tumor is Stage IV or Stage IIIb (with malignant pleural or pericardial effusion) at the time of signed informed consent (UICC/AJCC version 7)
-Patient has measurable or non-measurable disease according to
RECIST v1.1 criteria (for the Phase II portion, the patient must have measurable disease according to RECIST 1.1 criteria)
- Patient has an Eastern Cooperative Oncology
Group (ECOG) performance status = 1 that the investigator
believes is stable at the time of screening
- Patient has adequate bone marrow and organ function
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

- Patient has received any prior systemic therapies for metastatic NSCLC. Study treatment in this clinical trial must be the patient’s first systemic treatment for metastatic NSCLC. Patients are eligible if they received neo-adjuvant or adjuvant systemic therapy followed by a disease-free interval exceeding 12 months.
- Patient has symptomatic CNS metastases [patients with asymptomatic CNS metastases may participate in this trial. The patient must have completed any prior local treatment for CNS
metastases = 28 days prior to the start of study treatment
(including radiotherapy and/or surgery, or =14 days for
stereotactic radiosurgery)].
- Patient is currently receiving warfarin or other coumadin derived anticoagulant for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed.
- Patient is currently receiving treatment with drugs known to be moderate or strong inhibitors or inducers of isoenzyme CYP3A. The patient must have discontinued strong inducers for at least one week and must have discontinued strong inhibitors before the treatment is initiated. Switching to a different medication prior to
randomization is allowed.
- Patient has a medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (e.g. risk of doing harm to self or others) or patients with active severe personality disorders (defined according to DSM- IV) are not eligible. Note: for patients
with psychotropic treatments ongoing at baseline, the dose and the schedule should not be modified within the previous 6 weeks prior to start of study drug
- Patient has = CTCAE grade 3 anxiety
- Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL) -Patient who does not apply highly effective
contraception during the study and through the duration as
defined below after the final dose of study treatment.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Timepoint(s) of evaluation of this end point: Timepoint for DLT: Cycle 1 (21 days)<br>Timepoint for PFS: at randomization, every 6 weeks to the date of first document progression for up to 3 years;Main Objective: To determine the MTD/RP2D of buparlisib when administered orally in combination with every-3-week carboplatin and paclitaxel to adult patients with previously untreated Stage IIIb (with malignant pleural or pericardial effusion) or Stage IV NSCLC of<br>squamous histology;Secondary Objective: - Assess safety and tolerability<br>- Assess preliminary activity;Primary end point(s): - Number of Total Dose-limiting Toxicity (DLT) during dose escalation to determine Maximum Tolerated Dose (MTD)<br>- Progression Free Survival (PFS) as measured using RECIST 1.1

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1. Number of participants with best overall response rate (ORR) according to RECIST<br>2. Overall Survival Time<br>3. Time to overall response<br>4. Overall Safety and Tolerability of buparlisib (BKM120)<br>5. Change from baseline in QoL measured bu the functional assessment of EORTC QLQ-C-30 and lung cancer module (QLQ-LC-13)<br>6. Time to deterioration by the functional assessment of EORTC QLQ-C-30 and lung cancer module (QLQ-LC-13)<br>7. Buparlisib concentrations<br>8. Duration of overall response;Timepoint(s) of evaluation of this end point: Endpoints 1, 2, 3 and 8: every 6 weeks from randomization until first documented progression for up to 3 years<br>Endpoint 4: untill 30 days after last dose<br>Endpoints 5 and 6: screening, every 6 weeks until disease progression for up to 3 years<br>Endpoint 7: cycle 1 day 8 and day 15, cycle 2 day 1, cycle 7-cycle n day 1

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