Clinical trial NCT01820325: Safety and Efficacy of Buparlisib (BKM120) in Patients With Untreated Squamous Non-small Cell Lung Cancer
Official title: A Dose-finding Phase Ib Study Followed by a Randomized, Double-blind Phase II Study of Carboplatin and Paclitaxel With or Without Buparlisib in Patients With Previously Untreated Metastatic Non-small Cell Lung Cancer (NSCLC) of Squamous Histology
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Non-Small Cell Lunch Cancer
Keywords: Squamous non-small cell lung cancer
NSCLC
stage IV
BKM120
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2013-03-28
Enrollment: 6
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The Phase Ib part of the study aimed to determine the maximum tolerated dose/recommended Phase II dose (MTD/RP2D) of once daily buparlisib in combination with every-three-week carboplatin and paclitaxel in patients with previously untreated metastatic squamous NSCLC.

The purpose of the Phase II portion of the study was to assess the treatment effect of adding buparlisib versus buparlisib-matching placebo to every-three-week carboplatin and paclitaxel on progression free survival (PFS) in patients with previously untreated metastatic squamous NSCLC.

Detailed description: Based on the observation of DLTs and AEs, the safety profile of this investigational treatment was considered challenging requiring dose reductions/interruptions and even the evaluation of an alternative schedule of buparlisib administration. The study was early terminated, and the primary objective was not met. Therefore the phase ll portion of the study was never initiated.

Eligibility criteria: Inclusion Criteria:

* Patient has histologically and/or cytologically confirmed diagnosis of squamous NSCLC. Diagnosis of mixed squamous with a squamous component will be acceptable for enrollment.
* Patient has archival or new tumor tissue for the analysis of PI3K biomarkers
* Tumor is Stage IV 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

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 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.

Primary outcomes:
measure: Number of Total Dose-limiting Toxicity (DLT) During Dose Escalation to Determine Maximum Tolerated Dose (MTD)
timeFrame: Cycle 1 (21 days)
measure: Progression Free Survival (PFS) as measured using RECIST 1.1
timeFrame: Randomization, every 6 weeks to the date of first document progression for up to 3 years
Secondary outcomes:
measure: Number of Participants With Best Overall Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST)
timeFrame: Every 6 weeks from randomization until first documented progression for up to 3 years
measure: Overall Survival Time
timeFrame: Every 6 weeks from randomization until first documented progression for up to 3 years
measure: Time to overall response
timeFrame: Every 6 weeks from randomization until first documented progression for up to 3 years
measure: The Overall Safety and Tolerability of buparlisib (BKM120)
timeFrame: Screening, Until 30 days after last dose
measure: Change From Baseline in Quality of Life Measured by the Functional Assessment of EORTC QLQ- C-30 and lung cancer module (QLQ-LC-13)
timeFrame: Screening, Every 6 weeks until disease progression for up to 3 years
measure: Time to deterioration by the Functional Assessment of EORTC QLQ- C-30 and lung cancer module (QLQ-LC-13)
timeFrame: Screening, Every 6 weeks until disease progression for up to 3 years
measure: Buparlisib concentrations
timeFrame: Cycle 1 day 8 and 15, Cycle 2 day 1, Cycle 7-Cycle n, day 1
measure: Duration of overall response
timeFrame: Every 6 weeks from randomization until first documented progression for up to 3 years
measure: Characterize the PK of buparlisib under alternative dosing regimen when combined with paclitaxel and carboplatin in the target population
timeFrame: cycle 1 to 6 in Phase Ib portion
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Portland
country: United States
facility: Northwest Cancer Specialists Compass Oncology -BKM
state: Oregon
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Ulm
country: Germany
facility: Novartis Investigative Site
city: Napoli
country: Italy
facility: Novartis Investigative Site
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Madrid
country: Spain
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Vansteenkiste JF, Canon JL, De Braud F, Grossi F, De Pas T, Gray JE, Su WC, Felip E, Yoshioka H, Gridelli C, Dy GK, Thongprasert S, Reck M, Aimone P, Vidam GA, Roussou P, Wang YA, Di Tomaso E, Soria JC. Safety and Efficacy of Buparlisib (BKM120) in Patients with PI3K Pathway-Activated Non-Small Cell Lung Cancer: Results from the Phase II BASALT-1 Study. J Thorac Oncol. 2015 Sep;10(9):1319-1327. doi: 10.1097/JTO.0000000000000607.