Safety and Efficacy of BKM120 in Patients With Metastatic Non-small Cell Lung Cancer

Non-small Cell Lung Cancer Clinical Trial

— BASALT-1  

Official title:

An Open Label Two-stage Study of Orally Administered BKM120 in Patients With Metastatic Non-small Cell Lung Cancer With Activated PI3K Pathway

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01297491
• Other study ID #: CBKM120D2201
• Secondary ID: 2010-024011-14
• Status: Completed
• Phase: Phase 2
• First received: February 11, 2011
• Last updated: March 10, 2016
• Start date: May 2011
• Est. completion date: October 2014

Study information

• Verified date: March 2016
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaBelgium: Federal Agency for Medicinal Products and Health ProductsBrazil: National Health Surveillance AgencyCanada: Health CanadaFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesHungary: National Institute of PharmacyItaly: National Institute of HealthJapan: Pharmaceuticals and Medical Devices AgencySingapore: Health Sciences AuthoritySpain: Spanish Agency of MedicinesTaiwan: Department of HealthThailand: Food and Drug AdministrationTurkey: Ministry of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

The purpose of this two-stage phase II study is to assess the efficacy of BKM120, as measured by determining the progression free survival (PFS), in patients with pretreated metastatic Non-small Cell Lung Cancer (NSCLC) that exhibits PI3K pathway activation. BKM120 will be investigated in two groups of NSCLC patients according to the histology of the cancer: squamous and non-squamous.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed NSCLC with activated PI3K pathway

• Progressive disease after prior systemic antineoplastic treatment(s) for advanced NSCLC

• Archival or fresh tumor biopsy must be available for profiling

• Measurable and/or non-measurable disease as per RECIST 1.1 criteria

• Eastern Cooperative Oncology Group (ECOG) performance status = 2

• Adequate organ function as assessed by laboratory tests

Exclusion Criteria:

• Patient has received previous treatment with PI3K inhibitors

• Patient with squamous NSCLC has received more than one line of chemotherapy treatment for metastatic disease; patient with non-squamous NSCLC has received more than two lines of systemic antineoplastic treatment for metastatic disease

• Uncontrolled or symptomatic CNS metastases

• Concurrent use of any other approved or investigational antineoplastic agent

• Radiotherapy = 28 days prior to starting study drug

• Major surgery within 28 days prior to starting study drug

• History of clinically significant cardiac dysfunction, mood disorders, or poorly controlled diabetes mellitus

• Current treatment with medication that has a known risk to prolong the QT interval or inducing Torsades de Pointes

• Impairment of gastrointestinal (GI) function

• Chronic treatment with steroids or another immunosuppressive agent.

• Concurrent severe and/or uncontrolled medical condition

• Currently receiving Warfarin or another coumarin derivative

• Known history of HIV infection

• Sensory neuropathy with functional impairment (CTC grade 2 neuropathy, regardless of causality)

• Pregnancy, lactation, or breastfeeding

• Woman of child-bearing potential

Other protocol-defined inclusion/exclusion criteria may apply

Study Design

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Drug:
• BKM120
Buparlisib was supplied as 10mg or 50mg capsules. It was administered on a continuous once daily dosing schedule at a dose of 100 mg. The patient was dosed on a flat scale of mg/day and not adjusted to body weight or body surface area.

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Cordoba
Argentina	Novartis Investigative Site	Rio Negro	Viedma
Belgium	Novartis Investigative Site	Brussel
Belgium	Novartis Investigative Site	Charleroi
Belgium	Novartis Investigative Site	Genk
Belgium	Novartis Investigative Site	Leuven
Belgium	Novartis Investigative Site	Libramont
Brazil	Novartis Investigative Site	Barretos	SP
Brazil	Novartis Investigative Site	Florianopolis	SC
Brazil	Novartis Investigative Site	Rio de Janeiro	RJ
Brazil	Novartis Investigative Site	Salvador	BA
Brazil	Novartis Investigative Site	São Paulo	SP
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Vancouver	British Columbia
France	Novartis Investigative Site	Caen Cedex
France	Novartis Investigative Site	Creteil
France	Novartis Investigative Site	Marseille cedex 20
France	Novartis Investigative Site	Rennes
France	Novartis Investigative Site	Villejuif Cedex
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Gauting
Germany	Novartis Investigative Site	Grosshansdorf
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Koeln
Germany	Novartis Investigative Site	Nuernberg
Germany	Novartis Investigative Site	Oldenburg
Germany	Novartis Investigative Site	Recklinghausen
Hong Kong	Novartis Investigative Site	Hongkong
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Deszk
Hungary	Novartis Investigative Site	Mátraháza
Hungary	Novartis Investigative Site	Szolnok
Italy	Novartis Investigative Site	Avellino	AV
Italy	Novartis Investigative Site	Genova	GE
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Parma	PR
Italy	Novartis Investigative Site	Udine	UD
Japan	Novartis Investigative Site	Koto	Tokyo
Japan	Novartis Investigative Site	Kurashiki	Okayama
Netherlands	Novartis Investigative Site	Maastricht
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Alicante	Comunidad Valenciana
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Mataro	Cataluña
Spain	Novartis Investigative Site	Sabadell	Barcelona
Taiwan	Novartis Investigative Site	Tainan 704	Taiwan ROC
Taiwan	Novartis Investigative Site	Taipei	Taiwan ROC
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Chiang Mai
Turkey	Novartis Investigative Site	Altunizade
Turkey	Novartis Investigative Site	Izmir
United Kingdom	Novartis Investigative Site	Leicester
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Manchester
United Kingdom	Novartis Investigative Site	Northwood	Middlesex
United States	Virginia Oncology Associates VOA - Lake Wright (2)	*see Various Departments*	Virginia
United States	Emory University School of Medicine/Winship Cancer Institute Emory 2	Atlanta	Georgia
United States	University of Colorado Univ CO	Aurora	Colorado
United States	Massachusetts General Hospital Mass General	Boston	Massachusetts
United States	Roswell Park Cancer Institute Rosewell	Buffalo	New York
United States	Ironwood Cancer and Research Centers SC	Chandler	Arizona
United States	Medical University of South Carolina MUSC	Charleston	South Carolina
United States	Rush University Medical Center SC	Chicago	Illinois
United States	University of Chicago Medical Center Unvi Chi	Chicago	Illinois
United States	MetroHealth Medical Center Dept.ofMetroHealthMedCtr.(2)	Cleveland	Ohio
United States	Baylor Health Care System/Sammons Cancer Center Baylor Texas Oncology	Dallas	Texas
United States	Texas Oncology South Texas Oncology	Dallas	Texas
United States	U of TX Southwestern Medical Center - SimmonsCompCancerCtr Clinical Research Office	Dallas	Texas
United States	Karmanos Cancer Institute Wayne St Karmanos	Detroit	Michigan
United States	Duke University Medical Center Duke 2	Durham	North Carolina
United States	Highlands Oncology Group Dept of Highlands Oncology Grp	Fayetteville	Arkansas
United States	Rocky Mountain Cancer Centers Dept. of Rocky Mountain Cancer	Greenwood Village	Colorado
United States	University of Kansas Cancer Center Univ of KS	Kansas City	Kansas
United States	Cedars Sinai Medical Center Dept.of Cedars-Sinai Med. Ctr.	Los Angeles	California
United States	University of Wisconsin Univ WIsc 2	Madison	Wisconsin
United States	Hematology Oncology Associates of Northern New Jersey PA DeptofHem-OncofNorthern NJ (2)	Morristown	New Jersey
United States	Memorial Sloan Kettering Cancer Center Sloan Kettering	NY	New York
United States	University of Oklahoma Health Sciences Center Dept. of Oklahoma Univ. HSC	Oklahoma City	Oklahoma
United States	Arizona Oncology Associates Tucson (Rudasill & La Cholla)	Phoenix	Arizona
United States	University of Pittsburgh Medical Center SC-2	Pittsburgh	Pennsylvania
United States	Northwest Cancer Specialists Compass Oncology -BKM	Portland	Oregon
United States	University of California at San Diego, Moores Cancer Ctr SC	San Diego	California
United States	Mayo Clinic - Arizona Mayo Scottsdale AZ	Scottsdale	Arizona
United States	Washington University School of Medicine Washington University (16)	St. Louis	Missouri
United States	Overlook Hospital - Carol G Simon Cancer Center Carol G Simon	Summit	New Jersey
United States	H. Lee Moffitt Cancer Center & Research Institute H Lee Moffitt	Tampa	Florida
United States	Fallon Clinic at Worcester Medical Center Fallon Clinic Worcester Med	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Canada,  France,  Germany,  Hong Kong,  Hungary,  Italy,  Japan,  Netherlands,  Singapore,  Spain,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

References & Publications (1)

Vansteenkiste JF, Canon JL, Braud FD, 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS) Rate as Per Investigator Local Review Measured Using RECIST 1.1 of Patients at Week 12	PFS rate was defined as the percentage of participants who were progression free at 12 weeks. Participants were considered as a "success" for PFS rate evaluated at 12 weeks if they presented an overall response at their 2nd post-baseline tumor assessment.The enrollment into the study in either histology group would stop for futility if a PFS rate <50% at 12 weeks was observed.; No statistical analysis was planned for this primary outcome. The results of the primary objective was based on the data from the interim analysis that took place at the cut off dates: 10-Apr-2013 for non-squamous and 08-Jan-2014 for squamous group.	Week 12	No
Secondary	Overall Survival (OS) Using Kaplan-Meier Estimates	OS was defined as the time from start of study drug (Stage 1) until death from any cause. If a patient was not known to have died, survival was censored at the date of last contact.	Every 8 weeks up to 24 months	No
Secondary	Overall Response Rate (ORR) Based on Investigator Assessment	ORR was defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR). Complete response was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm. Partial response was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Analyses of response rates were performed based on investigators' assessments (as per RECIST 1.1 criteria). ORR included all patients with and without measurable disease at baseline.	Every 6 weeks up to 24 months	No
Secondary	Disease Control Rate (DCR)	DCR defined as the percentage of participants with best overall response of CR or PR or stable disease (SD). Complete response was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm. Partial response was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD.; Analyses of response rates were performed based on investigators' assessments (as per RECIST 1.1 criteria). DCR included all participants with and without measurable disease at baseline.	Every 6 weeks up tp 24 months	No
Secondary	Time to Response (TTR)	TTR for a participant was defined as the time from the first treatment date to the date of first documented confirmed CR or PR evaluation. The date of event was defined as the date of response that was first determined and not using the date the response was confirmed.	Every 6 weeks up to 24 months	No
Secondary	Duration of Response (DoR)	DoR was defined as the elapsed time between the date of first documented CR or PR response (not the date of confirmed response) and the following date of event defined as the first documented progression or death due to underlying cancer.	Every 6 weeks up to 24 months	No