BKM120 for Patients With PI3K-activated Tumors (SIGNATURE)

Modular Phase II Study to Link Targeted Therapy to Patients With Pathway Activated Tumors: Module 1 - BKM120 for Patients With PI3K-activated Tumors

The purpose of this signal seeking study was is to determine whether treatment with BKM120 demonstrates sufficient efficacy in select pathway-activated solid tumors and/or hematologic malignancies to warrant further study.

Study Overview

• Status: Completed
• Conditions: PI3K Pathway Activated Tumors
• Intervention / Treatment: Drug: BKM120

• Study Type: Interventional
• Enrollment (Actual): 146
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States
      • Arizona Oncology Associates HOPE Division
    • Sedona, Arizona, United States, 86336
      • Arizona Oncology Associates PC- HAL
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Highlands Oncology Group
  • California
    • Santa Monica, California, United States, 90403
      • Sarcoma Oncology Center
  • Colorado
    • Greenwood Village, Colorado, United States
      • Rocky Mountain Cancer Centers RMCC - Aurora
  • Connecticut
    • Norwalk, Connecticut, United States, 06856
      • Whittingham Cancer Center Norwalk Hospital
    • Norwich, Connecticut, United States, 06360
      • Eastern Connecticut Hematology & Oncology Associates The Norwich Cancer Center
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialists Dept of Oncology (2)
    • Orlando, Florida, United States, 32804
      • Florida Hospital Cancer Institute FL Hosp. Cancer Instit.
    • West Palm Beach, Florida, United States, 33401
      • Florida Cancer Specialists
  • Georgia
    • Athens, Georgia, United States, 30607
      • University Cancer & Blood Center, LLC
    • Newnan, Georgia, United States, 30265
      • Southeastern Regional Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Lurie Children's Hospital of Chicago Developmental Therapeutics
    • Decatur, Illinois, United States, 62526
      • Cancer Care Specialists of Central Illinois
    • Peoria, Illinois, United States, 61615-7828
      • Illinois Cancer Care P.C. IL. Cancer Care
    • Peoria, Illinois, United States, 61615-7828
      • Illinois Cancer Care P.C.
    • Schaumburg, Illinois, United States, 60173
      • Cancer Treatment Centers of America Southwestern Regional Med. Ctr
  • Indiana
    • South Bend, Indiana, United States, 46617
      • Northern Indiana Cancer Research Consortium No. Indiana Cancer Res.
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals & Clinics Regulatory Contact 2
  • Maine
    • Bangor, Maine, United States, 04401
      • Eastern Maine Medical Center Research Center SC
  • Massachusetts
    • Cambridge, Massachusetts, United States, 02138
      • Mount Auburn Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109 5271
      • Michigan Medicine University of Michigan Int. Medicine Oncology
    • Grand Rapids, Michigan, United States, 49546
      • Cancer and Hematology Centers of West Michigan Dept. of Oncology
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Minnesota Oncology Hematology, P.A. Minnesota Oncology Hematology
  • Nebraska
    • Omaha, Nebraska, United States, 68154
      • Nebraska Cancer Specialists Oncology Hematology West
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Comprehensive Cancer Centers
  • New Jersey
    • Morristown, New Jersey, United States, 07962
      • Hematology Oncology Associates of Northern New Jersey PA Regional Cancer Care Assoc.
  • New Mexico
    • Albuquerque, New Mexico, United States
      • Cancer Center at Presbyterian
  • New York
    • Albany, New York, United States, 12208
      • New York Oncology Hematology NY Onc Hem
  • North Carolina
    • Cary, North Carolina, United States, 27518
      • Waverly Hematology Oncology
    • Chapel Hill, North Carolina, United States, 27599-7600
      • University of N C at Chapel Hill Physician Office Building
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center Seeley G. Mudd Bldg.
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation Cleveland Clinic (19)
    • Columbus, Ohio, United States, 43219
      • Mid Ohio Oncology/Hematology Mark H. Zangmeister Center
  • Oregon
    • Bend, Oregon, United States, 97701
      • Bend Memorial Clinic Bend Mem. Clinic
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University Oregon Health & Science U (56)
    • Portland, Oregon, United States, 97210
      • Northwest Cancer Specialists Compass Oncology (36)
    • Salem, Oregon, United States, 97309
      • SALEM Health
  • Pennsylvania
    • Gettysburg, Pennsylvania, United States, 17325
      • Gettysburg Cancer Center
    • Natrona Heights, Pennsylvania, United States, 15065
      • West Penn Allegheny Oncology Network
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center UPMC
    • Willow Grove, Pennsylvania, United States, 19090
      • Abington Hematology Oncology Associates, Inc Abington Hem Onc Assoc (5)
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57104
      • Sanford University of South Dakota Medical Center Sanford Health
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Chattanooga Oncology and Hematology Assoicates, PC Chattanooga Oncology
    • Memphis, Tennessee, United States, 38120
      • West Cancer Clinic
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Dallas, Texas, United States, 75251
      • Texas Oncology P A Round Rock
    • Dallas, Texas, United States, 78246
      • Texas Oncology Sammons Cancer Center Sammons Cancer Center (10)
    • Fort Worth, Texas, United States, 76104
      • Texas Oncology, P.A. Texas Oncololgy, P.A. (8)
    • Houston, Texas, United States, 77024
      • Oncology Consultants Oncology Group
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center/University of Texas MD Anderson Cancer Center (3)
    • San Antonio, Texas, United States, 78229
      • Cancer Care Centers of South Texas HOAST CCC of So. TX-San Antonio (3)
    • Tyler, Texas, United States, 75702
      • Tyler Cancer Center
  • Utah
    • Murray, Utah, United States, 84157
      • Intermountain Medical Center Intermountain Healthcare
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists Virginia Cancer Specialists
    • Roanoke, Virginia, United States, 24018
      • Blue Ridge Research Center at Roanoke Neurological Center McKesson Specialty Care
  • Washington
    • Kennewick, Washington, United States, 99336
      • Kadlec Clinic Hematology and Oncology Kadlec Clinic Hematology & Onc
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties Hematology/Oncology
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient had a confirmed diagnosis of a solid tumor or hematological malignancy with the exception of endometrial cancer, glioblastoma, nonsmall cell lung cancer, prostate cancer or breast cancer.
• Patient's tumor was evaluated and pre-identified to have activation of the PI3K pathway, at a CLIA certified laboratory
• Patient must have received at least one prior treatment for recurrent metastatic and /or locally advanced disease and for whom no standard therapy options was anticipated to result in a durable remission.
• Patient must have had progressive and measurable disease as per RECIST 1.1. or other appropriate hematological guidelines
• Patient had an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1

Exclusion Criteria:

Patient had received previous treatment with BKM120 Patient had symptomatic CNS metastases Patient had mood disorder as outlined in Section 5 Patient had received chemotherapy or other anticancer therapy ≤ 4 weeks (6 weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug.

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: BKM120; BKM120 100 mg (oral gelatine capsules) was administered orally once daily starting from cycle 1 day 1 and will be dosed continuously every day for each 28- day cycle	Drug: BKM120; BKM120 100 mg (oral gelatine capsules) was administered orally once daily starting from cycle 1 day 1 and will be dosed continuously every day for each 28-day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participant Clinical Benefit Response Rate	Clinical benefit rate for patients with solid tumors will be assessed using RECIST 1.1 and will include responses of Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) at >=16 weeks. For hematologic tumors other appropriate hematological response criteria was applied. Response criteria: CR=Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm., PR=At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study, PD= At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline	Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response of Partial Response (PR) or Greater. PR=at Least a 30% Decrease in the Sum of Diameters of Target Lesions, Taking as Reference the Baseline Sum Diameters	Overall Response (OR) of Partial Response (PR) or greater is based on local investigator assessment. For patients with solid tumors, the assessment criteria will be RECIST 1.1 and will include responses of CR and/or PR. For hematologic tumors other appropriate hematological response criteria apply	baseline and every 8 weeks until disease progression or end of treatment, assessed up to 24 months
Progression-Free Survival - Number of Participants With an Event	Progression free survival (PFS) is defined as the time from the date of first dose to the date of first documented disease progression or relapse or death due to any cause	Every 8 Weeks until death, assessed up to 24 months
Progression-Free Survival (PFS)- Kaplan-Meier Estimates of PFS Timing in Months	Progression free survival (PFS) is defined as the time from the date of first dose to the date of first documented disease progression or relapse or death due to any cause	baseline up to 24 months
Progression-Free Survival (PFS)- Kaplan-Meier Estimates of PFS Rate in Percentages	Progression free survival (PFS) is defined as the time from the date of first dose to the date of first documented disease progression or relapse or death due to any cause.	baseline up to 24 months
Overall Survival - Number of Participants With an Event	Overall survival (OS) is defined as the time from the date of first dose to the date of death due to any cause. If a patient is not known to have died, survival time will be censored at the date of the last contact	Every 8 Weeks until death, assessed up to 24 months
Overall Survival (OS)- Kaplan-Meier Estimates of OS Timing in Months	Overall survival (OS) is defined as the time from the date of first dose to the date of death due to any cause. If a patient is not known to have died, survival time will be censored at the date of the last contact	baseline up to 24 months
Overall Survival (OS)- Kaplan-Meier Estimates of OS Rate in Percentages	Overall survival (OS) is defined as the time from the date of first dose to the date of death due to any cause. If a patient is not known to have died, survival time will be censored at the date of the last contact	baseline up to 30 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2013
• Primary Completion (Actual): September 26, 2016
• Study Completion (Actual): September 26, 2016

Study Registration Dates

• First Submitted: April 5, 2013
• First Submitted That Met QC Criteria: April 15, 2013
• First Posted (Estimate): April 16, 2013

Study Record Updates

• Last Update Posted (Actual): October 19, 2018
• Last Update Submitted That Met QC Criteria: October 18, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: AML; hematologic malignancy; ovarian; Solid tumor; malignancy; cervical; acute myelogenous leukemia; BKM120; signature; buparlisib; hepatobiliary; PI3K pathway activation; P13K activated tumors
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: CBKM120ZUS40