Safety and Efficacy of Buparlisib (BKM120) in Patients With Untreated Squamous Non-small Cell Lung Cancer

Overview[ - collapse ][ - ]

Purpose The Phase Ib part of the study aims 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 is 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.
ConditionNon-Small Cell Lunch Cancer
InterventionDrug: BKM120
Drug: placebo
Drug: Carboplatin
Drug: Paclitaxel
PhasePhase 1/Phase 2
SponsorNovartis Pharmaceuticals
Responsible PartyNovartis
ClinicalTrials.gov IdentifierNCT01820325
First ReceivedMarch 25, 2013
Last UpdatedFebruary 17, 2014
Last verifiedFebruary 2014

Tracking Information[ + expand ][ + ]

First Received DateMarch 25, 2013
Last Updated DateFebruary 17, 2014
Start DateSeptember 2013
Estimated Primary Completion DateDecember 2016
Current Primary Outcome Measures
  • Number of Total Dose-limiting Toxicity (DLT) During Dose Escalation to Determine Maximum Tolerated Dose (MTD) [Time Frame: Cycle 1 (21 days)] [Designated as safety issue: Yes]Determine the MTD and/or RP2D of daily buparlisib in combination with paclitaxel and carboplatin in patients with advanced or metastatic squamous NSCLC.
  • Progression Free Survival (PFS) as measured using RECIST 1.1 [Time Frame: Randomization, every 6 weeks to the date of first document progression for up to 3 years] [Designated as safety issue: No]Progression-free survival is defined as the time from randomization to the date of the first documented progression or death from any cause. The Kaplan-Meier estimate of the PFS survival function was contructed.
Current Secondary Outcome Measures
  • Number of Participants With Best Overall Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) [Time Frame: Every 6 weeks from randomization until first documented progression for up to 3 years] [Designated as safety issue: No]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 criteria. Per RECIST: CR, all detectable tumor has disappeared; PR, a >=30% decrease in the sum of the longest dimensions of the target lesions (TLs) taking as a reference the baseline sum, no worsening of non-TLs, and no new lesions; Progressive disease (PD), a >=20% increase in TLs, clearly worsening of non-TLs, or emergence of new lesions; Stable Disease (SD), small changes that do not meet previously given criteria.
  • Overall Survival Time [Time Frame: Every 6 weeks from randomization until first documented progression for up to 3 years] [Designated as safety issue: No]Overall survival (OS) time was measured from the start of study drug to the date of death due to any cause. If a patient was not known to have died, survival was censored at the date of last contact. Data was collected post treatment every 6 weeks until approximately 75% of patients have reached the survival endpoint (Phase I + Phase II).
  • Time to overall response [Time Frame: Every 6 weeks from randomization until first documented progression for up to 3 years] [Designated as safety issue: No]Time to overall response (TTR) 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. TTR will primarily be listed.
  • The Overall Safety and Tolerability of buparlisib (BKM120) [Time Frame: Screening, Until 30 days after last dose] [Designated as safety issue: Yes]Assessments consisted of recording all AEs and serious adverse events (SAEs), the regular monitoring of hematology, blood chemistry, vital signs, physical condition and body weight.
  • Change From Baseline in Quality of Life Measured by the Functional Assessment of EORTC QLQ- C-30 and lung cancer module (QLQ-LC-13) [Time Frame: Screening, Every 6 weeks until disease progression for up to 3 years] [Designated as safety issue: Yes]Quality of life (QoL) is evaluated using EORTC QLQ-C30 and QLQ-LC-13 scale. QLQ-L30 is composed of 30 items, whose responses range from 0 to 4. The QLQ-LC13 is used in conjucntion with the QLQ-C30 and provides information on an additional 13 items specifically relating to lung cancer. It incorporates one multi-item scale to assess dyspnea and a series of single-item scale to assess pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and haemoptysis. All the multi-item scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / QoL represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems.
  • Time to deterioration by the Functional Assessment of EORTC QLQ- C-30 and lung cancer module (QLQ-LC-13) [Time Frame: Screening, Every 6 weeks until disease progression for up to 3 years] [Designated as safety issue: Yes]Time to definitive 10% deterioration in the global health status / QoL, physical functioning, emotional functioning, social functioning, and lung cancer symptoms scales will be assessed in the two treatment arms.
  • Buparlisib concentrations [Time Frame: Cycle 1 day 8 and 15, Cycle 2 day 1, Cycle 7-Cycle n, day 1] [Designated as safety issue: No]Pharmacokinetics of buparlisib will be investigated in order to investigate any unexpected impact of carboplatin and paclitaxel therapy on the pharmacokinetics of buparlisib. For this purpose, plasma samples will be collected during phase II of the trial. In one set of the population (N=40) samples will be collected according to a sparse sampling strategy over the entire course of the treatment, to allow a proper estimate of the pharmacokinetic parameters. In addition, trough samples should be collected, for the whole population, for measurement of buparlisib/placebo. These additional samples will allow investigating potential PK/PD relationships for various therapeutic or adverse outcome in the whole study population.
  • Duration of overall response [Time Frame: Every 6 weeks from randomization until first documented progression for up to 3 years] [Designated as safety issue: No]Duration of overall response (DR) 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. DR will primarily be listed. DR may be described using Kaplan-Meier curves and any related statistics if relevant and will be presented by treatment group in phase II. These analyses will be performed on the responder subset, i.e. patients with a confirmed complete response (CR) or partial response (PR).
  • Characterize the PK of buparlisib under alternative dosing regimen when combined with paclitaxel and carboplatin in the target population [Time Frame: cycle 1 to 6 in Phase Ib portion] [Designated as safety issue: No]Buparlisib concentrations and model-based PK derived parameters

Descriptive Information[ + expand ][ + ]

Brief TitleSafety and Efficacy of Buparlisib (BKM120) in Patients With Untreated Squamous Non-small Cell Lung Cancer
Official TitleA 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
Brief Summary
The Phase Ib part of the study aims 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 is 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 DescriptionNot Provided
Study TypeInterventional
Study PhasePhase 1/Phase 2
Study DesignAllocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
ConditionNon-Small Cell Lunch Cancer
InterventionDrug: BKM120
Drug: placebo
Placebo + Carboplatin + Paclitaxel
Drug: Carboplatin
Drug: Paclitaxel
Study Arm (s)
  • Experimental: Buparlisib + Carboplatin + Paclitaxel
    Buparlisib + Carboplatin + Paclitaxel (100 patients)
  • Placebo Comparator: Placebo + Carboplatin + Paclitaxel
    Placebo + Carboplatin + Paclitaxel (100 patients)

Recruitment Information[ + expand ][ + ]

Recruitment StatusRecruiting
Estimated Enrollment220
Estimated Completion DateDecember 2016
Estimated Primary Completion DateDecember 2016
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.
GenderFemale
Ages18 Years
Accepts Healthy VolunteersNo
ContactsContact: Novartis Pharmaceuticals
1-888-669-6682
Location CountriesUnited States, Argentina, Australia, Belgium, Brazil, Canada, Czech Republic, France, Germany, Hungary, Italy, Russian Federation, South Africa, Spain, Taiwan, Turkey, United Kingdom

Administrative Information[ + expand ][ + ]

NCT Number NCT01820325
Other Study ID NumbersCBKM120D2204
Has Data Monitoring CommitteeYes
Information Provided ByNovartis
Study SponsorNovartis Pharmaceuticals
CollaboratorsNot Provided
Investigators Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Verification DateFebruary 2014

Locations[ + expand ][ + ]

Highlands Oncology Group SC-1
Fayetteville, Arkansas, United States, 72703
Contact: Tia Hesington | 479-936-9900 | thesington@hogonc.com
Principal Investigator: Eric S. Schaefer
Recruiting
USC Norris Cancer Center LAC USC Medical Center
Los Angeles, California, United States, 90033
Contact: Eduardo Mejia | 323-865-3962 | mejia_e@med.usc.edu
Principal Investigator: Barbara J. Gitlitz
Not yet recruiting
Rocky Mountain Cancer Centers Rocky Mountain Cancer Centers
Greenwood Village, Colorado, United States
Contact: Roxanne Riggs | 303-388-4876 | roxanne.riggs@usoncology.com
Principal Investigator: Robert M. Jotte
Recruiting
Georgetown University/Lombardi Cancer Center Georgetown Univ. Medical Ctr.
Washington, District of Columbia, United States, 20007
Contact: Rebecca Eberle | 202-687-5791 | ree28@georgetown.edu
Principal Investigator: Giuseppe Giaccone
Not yet recruiting
H. Lee Moffitt Cancer Center & Research Institute H Lee Moffitt
Tampa, Florida, United States, 33612
Contact: Jeff L. Jorski | 813-745-6895 | jeff.jorski@moffitt.org
Principal Investigator: Jhanelle Gray
Not yet recruiting
Rush University Medical Center Rush University
Chicago, Illinois, United States, 60612
Contact: Dawn Paulsen | 312-563-4593 | dawn_paulsen@rush.edu
Principal Investigator: Mary J Fidler
Not yet recruiting
University of Kansas Cancer Center Medical Pavilion
Kansas City, Kansas, United States, 66160
Contact: Collins Julie | +1 913 588 0545 | jcollins4@kumc.edu
Principal Investigator: Chao Hui Huang
Not yet recruiting
Reliant Medical Group Reliant Medical Group
Worchester, Massachusetts, United States, 01608
Contact: Sonia Martinath | sonia.martinath@reliantmedicalgroup.org
Principal Investigator: Saleem Khanani
Recruiting
Montefiore Medical Center SC BKM120 D2204 / D2205
Bronx, New York, United States, 10461
Contact: Srkantha Gajavelli | 718-405-8539 | sgajavel@montefiore.org
Principal Investigator: Bilal Piperdi
Not yet recruiting
Roswell Park Cancer Institute Rosewell
Buffalo, New York, United States, 14263
Contact: Carol Skelly | 716-845-4886 | carl.skelly@roswellpark.org
Principal Investigator: Grace Dy
Not yet recruiting
Sanford Research/USD-Fargo
Fargo, North Dakota, United States, 58122
Withdrawn
Northwest Cancer Specialists Compass Oncology -BKM
Portland, Oregon, United States, 97210
Contact: Denise M. Hill | 360-449-6522 | denise.hill@usoncology.com
Principal Investigator: David A. Smith
Recruiting
Medical University of South Carolina MUSC
Charleston, South Carolina, United States, 29425
Withdrawn
Sanford Research Alick Building
Sioux Falls, South Dakota, United States, 57104
Contact: Tammy A Hein | 605-328-1376 | Tammy.A.Hein@Sanfordhealth.org
Principal Investigator: Miroslaw Mazurczak
Not yet recruiting
Tennessee Cancer Specialists Center for Biomedical Research
Knoxville, Tennessee, United States, 37909
Contact: Erica Cox | 865-934-2675 | ecox@biomed-research.com
Principal Investigator: Russell F DeVore
Not yet recruiting
Sarah Cannon Research Institute BKM120D2204/BKM120D2205
Nashville, Tennessee, United States, 37203
Contact: Emily Angarole | 615-524-4086 | Emily.angarole@scresearch.net
Principal Investigator: David R. Spigel
Not yet recruiting
Vanderbilt Ingram Cancer Center SC (CTSR)
Nashville, Tennessee, United States, 37203
Contact: BJ Broome | 615-875-0060 | barbara.j.broome@vanderbilt.edu
Principal Investigator: Leora Horn
Not yet recruiting
US Oncology Central Monitoring
Dallas, Texas, United States, 75246
Withdrawn
Texas Oncology, P.A.
Fort Worth, Texas, United States, 76104
Contact: Ron Schoenfeldt | 817-850-2000 | Ron.schoenfeldt@McKesson.com
Principal Investigator: Stephen L. Richey
Recruiting
University of Texas Health Science Center Univ.TX Memorial Herman Cancer
Houston, Texas, United States, 77030
Contact: Susan Cooper | 832-325-7308 | susan.cooper@uth.tmc.edu
Principal Investigator: Shan Guo
Not yet recruiting
Institute of Oncology Hematology
Laredo, Texas, United States, 78041
Contact: Noe Garcia | 956-753-7839 | ngarcia@stexresearch.com
Principal Investigator: Eduardo Miranda
Not yet recruiting
Virginia Oncology Associates BKM120D2205/BKM120D2204
Norfolk, Virginia, United States, 23502
Contact: Gabrielle Whalen | 757-213-5658 | gabrielle.whalen@usocology.com
Principal Investigator: Paul Conkling
Recruiting
Novartis Investigative Site
Bahía Blanca, Buenos Aires, Argentina, B8001HXM
Not yet recruiting
Novartis Investigative Site
Mar del Plata, Buenos Aires, Argentina, B7600CTO
Not yet recruiting
Novartis Investigative Site
Rosario, Santa Fe, Argentina, S2000KZE
Not yet recruiting
Novartis Investigative Site
Capital Federal, Argentina, 1417
Withdrawn
Novartis Investigative Site
Clayton, Victoria, Australia, 3168
Not yet recruiting
Novartis Investigative Site
Brussel, Belgium, 1090
Not yet recruiting
Novartis Investigative Site
Liege, Belgium, 4000
Not yet recruiting
Novartis Investigative Site
Liège, Belgium, 4000
Not yet recruiting
Novartis Investigative Site
Belo Horizonte, MG, Brazil, 30150-270
Not yet recruiting
Novartis Investigative Site
Recife, PE, Brazil, 50070-550
Not yet recruiting
Novartis Investigative Site
Rio de Janiero, RJ, Brazil, 20231-050
Not yet recruiting
Novartis Investigative Site
Ijuí, RS, Brazil, 98700-000
Not yet recruiting
Novartis Investigative Site
Porto Alegre, RS, Brazil, 90610-000
Not yet recruiting
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Barretos, SP, Brazil, 14784-400
Not yet recruiting
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São Paulo, SP, Brazil, 01246-000
Not yet recruiting
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Edmonton, Alberta, Canada, T6G 1Z2
Not yet recruiting
Novartis Investigative Site
Ottawa, Ontario, Canada, KIH 7W9
Withdrawn
Novartis Investigative Site
Toronto, Ontario, Canada, M5G 1Z6
Recruiting
Novartis Investigative Site
Brno, Czech Republic, 65653
Not yet recruiting
Novartis Investigative Site
Prague 8, Czech Republic, 180 00
Not yet recruiting
Novartis Investigative Site
Creteil, France, 94000
Not yet recruiting
Novartis Investigative Site
Villejuif Cedex, France, 94805
Not yet recruiting
Novartis Investigative Site
Freiburg, Germany, 79106
Recruiting
Novartis Investigative Site
Ulm, Germany, 89081
Recruiting
Novartis Investigative Site
Budapest, Hungary, 1121
Withdrawn
Novartis Investigative Site
Gyor, Hungary, 9023
Withdrawn
Novartis Investigative Site
Nyiregyhaza, Hungary, 4400
Not yet recruiting
Novartis Investigative Site
Pecs, Hungary, 7624
Withdrawn
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Veszprém, Hungary, 8200
Not yet recruiting
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Zalaegerszeg-Pózva, Hungary, 8900
Not yet recruiting
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Catanzaro, CZ, Italy, 88100
Not yet recruiting
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Genova, GE, Italy, 16132
Not yet recruiting
Novartis Investigative Site
Monza, MB, Italy, 20900
Recruiting
Novartis Investigative Site
Milano, MI, Italy, 20141
Not yet recruiting
Novartis Investigative Site
Milano, MI, Italy, 20133
Not yet recruiting
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Rozzano, MI, Italy, 20089
Not yet recruiting
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Padova, PD, Italy, 35100
Not yet recruiting
Novartis Investigative Site
Napoli, Italy, 80131
Recruiting
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Nizhniy Novgorod, Russia, Russian Federation
Not yet recruiting
Novartis Investigative Site
Chelyabinsk, Russian Federation, 454087
Not yet recruiting
Novartis Investigative Site
Sankt-Peterburg, Russian Federation, 197022
Not yet recruiting
Novartis Investigative Site
St. Petersburg, Russian Federation, 197758
Not yet recruiting
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Bloemfontein, South Africa, 9300
Not yet recruiting
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Pretoria, South Africa, 0027
Not yet recruiting
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Pretoria, South Africa, 0002
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Barcelona, Cataluña, Spain, 08035
Recruiting
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Madrid, Spain, 28046
Recruiting
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Kuei-Shan Chiang, Taoyuan/ Taiwan ROC, Taiwan, 33305
Not yet recruiting
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Niaosong Township, Taiwan, 83301
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Taichung, Taiwan, 40447
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Gaziantep, Turkey, 27070
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Istanbul, Turkey, 34303
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Izmir, Turkey, 35040
Not yet recruiting
Novartis Investigative Site
Sihhiye/Ankara, Turkey, 06100
Not yet recruiting
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Birmingham, United Kingdom, B9 5SS
Not yet recruiting
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Leicester, United Kingdom, LE1 5WW
Not yet recruiting
Novartis Investigative Site
Wirral, United Kingdom, CH63 3JY
Suspended