Clinical trial NCT01911325: Phase II Study of Buparlisib + Docetaxel in Advanced or Metastatic Squamous Non-small Cell Lung Cancer (NSCLC) Patients
Official title: A Phase Ib/II Study of Docetaxel With or Without Buparlisib as Second Line Therapy for Patients With Advanced or Metastatic Squamous Non-small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Squamous Non-small Cell Lung Cancer
Keywords: Squamous non-small cell lung cancer
NSCLC
Docetaxel
Buparlisib
BKM120
Metastatic
Stage IIIb
Stage IV
PI3K inhibitor
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2013-07-30
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multi-center, open-label Phase Ib dose escalation part followed by a randomized double-blinded placebo controlled Phase II part.

The Phase Ib part will determine the Maximum Tolerated Dose (MTD)/Recommended Phase II Dose (RP2D) of buparlisib in combination with docetaxel. Subsequently the MTD/RP2D will be investigated in a Phase II randomized trial in patients with advanced or metastatic squamous NSCLC.

Detailed description: Based on an overall review of safety and preliminary efficacy data done on 01-Dec-2014 showing marginal anti-tumor activity and newly emerged treatment options, a decision was taken to stop further development of this combination in patients with advanced or metastatic squamous NSCLC and Phase II of the study was not conducted.

Eligibility criteria: Inclusion Criteria:

* Patient is an adult ≥ 18 years old at the time of informed consent
* 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 received one prior approved regimen of platinum-based chemotherapy (excluding a docetaxel-containing regimen) for advanced or metastatic (Stage IIIb or Stage IV) squamous NSCLC, followed by disease progression. A drug provided as maintenance therapy following cytotoxic chemotherapy will be considered to be part of that regimen.

Note: Patients who received paclitaxel therapy are eligible for this trial. •Patient has adequate tumor tissue (either archival or new tumor biopsy) for the analysis of PI3K-related biomarkers.

Enrollment in the Phase II part of the study is contingent on the central laboratory confirming receipt of an adequate amount of tissue including sufficient DNA for analysis.

•Patient has measurable or non-measurable disease according to RECIST version 1.1 criteria.

Phase II only: Patient must have at least one measurable lesion as per RECIST criteria.

* Patient has an ECOG performance status ≤ 1
* Patient has adequate bone marrow and organ function

Exclusion Criteria:

* Patient has received previous treatment with a PI3K or AKT inhibitor
* Patient has symptomatic Central Nervous System (CNS) metastases Patients with asymptomatic CNS metastases may participate in this trial. The patient must have completed prior local treatment, if any, for CNS metastases ≥ 28 days prior to the start of study treatment (including radiotherapy and/or surgery, or ≥ 14 days for stereotactic radiosurgery).
* Patient has a score ≥ 12 on the PHQ-9 questionnaire.
* Patient selects a response of "1, 2 or 3" to question number 9 on the PHQ-9 questionnaire regarding potential for suicidal thoughts or ideation (independent of the total score of the PHQ-9).
* Patient has a GAD-7 mood scale score ≥ 15.
* 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 or patients with active severe personality disorders.
* Patient has ≥ CTCAE grade 3 anxiety

Primary outcomes:
measure: Phase Ib: Incidence of Dose Limiting Toxicities (DLTs) in Cycle 1
timeFrame: Day 21
measure: Phase II: Progression Free Survival (PFS)
timeFrame: After 70 PFS events have been observed at 9 months after patient enrollment
Secondary outcomes:
measure: Number of patients with at least one adverse event.
timeFrame: Up to 30 days after the last dose
measure: Number of patients with laboratory abnormalities.
timeFrame: Up to 30 days after the last dose
measure: Overall Survival (OS)
timeFrame: Treatment start (phase Ib)/randomization (phase II), every 6 weeks to the date of first document progression for up to 3 years
measure: Overall response rate (ORR)
timeFrame: Every 6 weeks from randomization until first documented progression for up to 3 years
measure: Time to response (ToR)
timeFrame: Every 6 weeks from randomization until first documented progression for up to 3 years
measure: Duration of response (DR)
timeFrame: Every 6 weeks from randomization until first documented progression for up to 3 years
measure: Change in electrocardiogram (ECG) and cardiac imaging
timeFrame: Up to 30 days after the last dose
measure: Changes in vital signs
timeFrame: Up to 30 days after the last dose
measure: Shift in ECOG performance status
timeFrame: Baseline, worst post-baseline result at day 1 of every cycle and at end of study treatment (3 years)
measure: Change in Mood scales
timeFrame: Up to 30 days after the last dose
measure: Time to definitive 10% deterioration in the global health status/quality of life (QOL) scale score of the EORTC QLQ-C30
timeFrame: Baseline, Every 6 weeks until disease progression for up to 3 years
measure: Change in the global health status/quality of life (QOL) scale score of the EORTC QLQ-C30
timeFrame: Baseline, Every 6 weeks until disease progression for up to 3 years
measure: Docetaxel and buparlisib plasma concentrations
timeFrame: Cycle 1 day 8 and 15, Cycle 2-Cycle n day 1
measure: PFS Phase Ib
timeFrame: at 3 months after patient enrollment, every 6 weeks until disease progression for up to 3 years
Other outcomes:
Locations:
city: Fayetteville
country: United States
facility: Highlands Oncology Group SC-1
state: Arkansas
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute H Lee Moffitt
state: Florida
city: Worcester
country: United States
facility: Reliant Medical Group Reliant Medical Group
state: Massachusetts
city: Norfolk
country: United States
facility: Virginia Oncology Associates Virginia Oncology Assoc. (2)
state: Virginia
city: Charleroi
country: Belgium
facility: Novartis Investigative Site
city: Mons
country: Belgium
facility: Novartis Investigative Site
city: Creteil
country: France
facility: Novartis Investigative Site
city: Saint Herblain cedex
country: France
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Heidelberg
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Monza
country: Italy
facility: Novartis Investigative Site
state: MB
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Stockholm
country: Sweden
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: