BKM120 as Second-line Therapy for Advanced Endometrial Cancer

A Phase II, Single-arm Study of Orally Administered BKM120 as Second-line Therapy in Patients With Advanced Endometrial Carcinoma

This is a prospective multi-center, open-label, single arm, Phase II study to investigate the safety and efficacy of BKM120 in patients with advanced endometrial carcinoma whose disease progressed on or after a first-line antineoplastic treatment. Patients will receive BKM120 orally at a dose of 100 mg/day. Availability of tumor specimen (either archival tissue or a fixed fresh biopsy) is mandatory for assessment of the PI3K (Phosphatidylinositol 3 Kinase (PI3K) pathway activation status.

Study Overview

• Status: Completed
• Conditions: Advanced Endometrial Cancer
• Intervention / Treatment: Drug: BKM120

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Parkville, Victoria, Australia, 3050
      • Novartis Investigative Site
• Belgium
  • Leuven, Belgium, 3000
    • Novartis Investigative Site
  • Liege, Belgium, 4000
    • Novartis Investigative Site
  • Wilrijk, Belgium, 2610
    • Novartis Investigative Site
• Brazil
  • RJ
    • Rio de Janeiro, RJ, Brazil, 20220410
      • Novartis Investigative Site
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • Novartis Investigative Site
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M5G 2M9
      • Novartis Investigative Site
  • Quebec
    • Montreal, Quebec, Canada, H2L 4M1
      • Novartis Investigative Site
• France
  • Le Mans Cedex, France, 72015
    • Novartis Investigative Site
  • Lyon Cedex, France, 69373
    • Novartis Investigative Site
  • Nice Cedex 2, France, 06189
    • Novartis Investigative Site
  • Toulouse Cedex 9, France, 31059
    • Novartis Investigative Site
• Germany
  • Berlin, Germany, 10367
    • Novartis Investigative Site
  • Berlin, Germany, 13353
    • Novartis Investigative Site
  • Köln, Germany, 50937
    • Novartis Investigative Site
  • Mainz, Germany, 55131
    • Novartis Investigative Site
• Italy
  • Bologna, Italy, 40138
    • Novartis Investigative Site
  • Napoli, Italy, 80131
    • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20141
      • Novartis Investigative Site
  • PN
    • Aviano, PN, Italy, 33081
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00168
      • Novartis Investigative Site
• Japan
  • Aichi
    • Nagoya, Aichi, Japan, 464-8681
      • Novartis Investigative Site
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • Novartis Investigative Site
    • Minato-ku, Tokyo, Japan, 105-8471
      • Novartis Investigative Site
• Poland
  • Warszawa, Poland, 00973
    • Novartis Investigative Site
• Russian Federation
  • St. Petersburg, Russian Federation, 198255
    • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 229899
    • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28046
    • Novartis Investigative Site
  • Madrid, Spain, 28033
    • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08036
      • Novartis Investigative Site
  • Comunidad Valenciana
    • Valencia, Comunidad Valenciana, Spain, 46026
      • Novartis Investigative Site
    • Valencia, Comunidad Valenciana, Spain, 46009
      • Novartis Investigative Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • St. Joseph's Hospital & Medical Center St Joseph's
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Highlands Oncology Group Dept of Highlands Oncology Grp
  • New Jersey
    • Morristown, New Jersey, United States, 07962
      • Morristown Memorial Hospital MMH
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Carolinas HealthCare Systems Blumenthal Cancer Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center OU Health
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute SCRI (2)
  • Texas
    • Bedford, Texas, United States, 76022
      • Texas Oncology, P.A. Austin
    • San Antonio, Texas, United States, 78258
      • South Texas Oncology and Hematology, PA South Tex Onc
  • Washington
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest CC Northwest- Spokane South(3)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• ECOG (Eastern Cooperative Oncology Group) performance status ≤ 2
• histologically confirmed diagnosis of advanced endometrial carcinoma with available tissue specimen for identification of PI3K pathway activation (archival tissue or a fixed fresh biopsy)
• one prior line of antineoplastic treatment with a cytotoxic agent
• objective progression of disease after prior treatment and at least one measurable lesion as per RECIST criteria
• adequate bone marrow and organ function

Exclusion Criteria:

• previous treatment with PI3K and/or mTOR inhibitors
• symptomatic CNS metastases
• concurrent malignancy or malignancy within 3 years of study enrollment
• Active mood disorder as judged by investigator or medically documented history of mood disorder (e.g. major depressive episode, bipolar disorder, obsessive-compulsive disorder, schizophrenia, etc.), ≥ CTCAE grade 3 anxiety
• pelvic and/or para-aortic radiotherapy ≤ 28 days prior to enrollment in the study
• poorly controlled diabetes mellitus (HbA1c > 8 %)
• history of cardiac dysfunction or active cardiac disease as specified in the protocol
• impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKM120

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: All Patients	Drug: BKM120; Other Names: Buparlisib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Overall Response Rate (BORR) According to PI3K Activation Pathway Status	BOR was determined based on investigator assessment of overall lesion response using RECIST criteria guidelines. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) According to PI3K Activation Pathway Status	PFS is defined as the time from start of treatment to the date of first documented progression or death due to any cause. If a patient has not had an event, PFS will be censored at the date of last adequate tumor assessment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.	24 months
Overall Survival (OS) According to PI3K Activation Pathway Status	Overall survival (OS) was defined as the time from start of treatment to the date of death due to any cause. If a patient is not known to have died, survival was censored at the last date of contact. From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 10 months	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 10 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: January 26, 2011
• First Submitted That Met QC Criteria: February 2, 2011
• First Posted (Estimate): February 3, 2011

Study Record Updates

• Last Update Posted (Actual): May 30, 2019
• Last Update Submitted That Met QC Criteria: May 20, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: second-line treatment; PI3K pathway; Advanced endometrial cancer
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Endometrial Neoplasms
• Other Study ID Numbers: CBKM120C2201; 2010-022015-19 (EudraCT Number)