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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
27
Highlands Oncology Group SC-1
Fayetteville, Arkansas, United States
H. Lee Moffitt Cancer Center & Research Institute H Lee Moffitt
Tampa, Florida, United States
Phase Ib: Incidence of Dose Limiting Toxicities (DLTs) in Cycle 1
To determine the maximum tolerated dose/recommended phase ll dose (MTD/RP2D) of buparlisib in combination with docetaxel by assessing the incidence of DLTs in Cycle 1; Cycle 1 = 21 days
Time frame: Day 21
Phase II: Progression Free Survival (PFS)
PFS as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. To estimate the treatment effect of docetaxel and buparlisib or placebo on PFS in patients with advanced or metastatic squamous NSCLC.
Time frame: After 70 PFS events have been observed at 9 months after patient enrollment
Number of patients with at least one adverse event.
Time frame: Up to 30 days after the last dose
Number of patients with laboratory abnormalities.
Time frame: Up to 30 days after the last dose
Overall Survival (OS)
Overall survival (OS) time is measured from the start of study drug to the date of death due to any cause. If a patient is not known to have died, survival will be censored at the date of last contact. Data will be collected post treatment every 6 weeks until approximately 75% of patients have reached the survival endpoint (Phase I + Phase II)
Time frame: Treatment start (phase Ib)/randomization (phase II), every 6 weeks to the date of first document progression for up to 3 years
Overall response rate (ORR)
Overall response is the number of participants who had a complete response (CR) or a partial response (PR) based on local investigator's assessment of RECIST 1.1 criteria.
Time frame: Every 6 weeks from randomization until first documented progression for up to 3 years
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Reliant Medical Group Reliant Medical Group
Worcester, Massachusetts, United States
Virginia Oncology Associates Virginia Oncology Assoc. (2)
Norfolk, Virginia, United States
Novartis Investigative Site
Charleroi, Belgium
Novartis Investigative Site
Mons, Belgium
Novartis Investigative Site
Créteil, France
Novartis Investigative Site
Saint-Herblain, France
Novartis Investigative Site
Frankfurt, Germany
Novartis Investigative Site
Heidelberg, Germany
...and 6 more locations
Time to response (ToR)
Time to overall response is defined as the time from the date of first drug intake in Phase Ib and from the date of randomization in Phase II to the date of first documented response.
Time frame: Every 6 weeks from randomization until first documented progression for up to 3 years
Duration of response (DR)
Duration of overall response is defined as the elapsed time between the date of first documented response and the following date of event defined as the first documented progression or death due to underlying cancer.
Time frame: Every 6 weeks from randomization until first documented progression for up to 3 years
Change in electrocardiogram (ECG) and cardiac imaging
Time frame: Up to 30 days after the last dose
Changes in vital signs
Time frame: Up to 30 days after the last dose
Shift in ECOG performance status
cycle = 21 days; end of treatment is defined as 15 days after treatment discontinuation; There is no treatment duration as patients continue to receive drug till toxicity or they withdraw consent
Time frame: Baseline, worst post-baseline result at day 1 of every cycle and at end of study treatment (3 years)
Change in Mood scales
Time frame: Up to 30 days after the last dose
Time to definitive 10% deterioration in the global health status/quality of life (QOL) scale score of the EORTC QLQ-C30
Date of event is defined as at least 10% relative to baseline worsening of the corresponding scale score or death due to any cause
Time frame: Baseline, Every 6 weeks until disease progression for up to 3 years
Change in the global health status/quality of life (QOL) scale score of the EORTC QLQ-C30
Change in the domain scores
Time frame: Baseline, Every 6 weeks until disease progression for up to 3 years
Docetaxel and buparlisib plasma concentrations
Time frame: Cycle 1 day 8 and 15, Cycle 2-Cycle n day 1
PFS Phase Ib
PFS as per RECIST 1.1
Time frame: at 3 months after patient enrollment, every 6 weeks until disease progression for up to 3 years