A Study of the Experimental Drug BKM120 With Paclitaxel in Patients With HER2 Negative, Locally Advanced or Metastatic Breast Cancer, With or Without PI3K Activation
- Conditions
- Breast Cancer
- Interventions
- Registration Number
- NCT01572727
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
This study evaluated whether the addition of daily BKM120 to weekly paclitaxel was effective and safe in treating patients with HER2- locally advanced or metastatic breast cancer.
- Detailed Description
Based on the efficacy results at the time of the interim analyses, the DMC recommended stopping the study at Phase II during the interim as it met the protocol pre-specified futility criteria. Consequently, the Phase III portion of the study was not conducted.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 416
- Breast cancer that is locally advanced or metastatic
- HER2 negative disease, and a known hormone receptor status - ER/PgR (common breast cancer classification tests)
- A tumor sample must be shipped to a central lab for identification of biomarkers (PI3K activation status) before randomization
- Adequate bone marrow and organ function
- Measurable or non-measurable disease
- Prior chemotherapy for locally advanced or metastatic disease
- Previous treatment with PI3K or AKT inhibitors
- Patient has symptomatic CNS metastases
- Concurrent malignancy or malignancy within 3 years of study enrollment
- Hematopoietic colony-stimulating growth factors or radiation within 2-4 weeks prior to starting study drug
- Increasing or chronic treatment (> 5 days) with corticosteroids or another immunosuppressive agent
- Active heart (cardiac) disease as defined in the protocol
- Known hypersensitivity or contraindications to use paclitaxel
- Pregnant or nursing (lactating) woman
- Certain scores on an anxiety and depression mood questionaire given at screening
- Other protocol defined criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description BKM120 and paclitaxel BKM120 Adult females with histologically confirmed, inoperable, locally advanced or metastatic HER2- BC who received study drug plus paclitaxel. Placebo and paclitaxel Paclitaxel Adult females with histologically confirmed, inoperable, locally advanced or metastatic HER2- BC who received placebo plus paclitaxel. Placebo and paclitaxel BKM120 matching placebo Adult females with histologically confirmed, inoperable, locally advanced or metastatic HER2- BC who received placebo plus paclitaxel. BKM120 and paclitaxel Paclitaxel Adult females with histologically confirmed, inoperable, locally advanced or metastatic HER2- BC who received study drug plus paclitaxel.
- Primary Outcome Measures
Name Time Method Progression-free Survival (PFS)Assessed by Local Investigator's Assessment (Phase ll) Every 8 weeks from randomization until disease progression up to 10 months after futility was analyzed PFS was defined as the time from the date of randomization to the date of the event, defined as the first radiologically documented disease progression or death due to any cause. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), 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.
- Secondary Outcome Measures
Name Time Method Overall Survival by Kaplan-Meier Estimate (Phase ll) every 3 months until death, lost to follow-up, or withdrawal of consent to survival follow-up, up to 10 months after futility was analyzed Overall survival (OS) was defined as the time from date of randomization to date of death due to any cause. If a patient was not known to have died by the date of analysis cut-off, OS was censored at the date of last contact.
Overall Response Rate (Phase ll) every 8 weeks after randomization Up to 3 months after end of Treatment Percentage of patients with best overall response of complete response (CR) or partial response (PR) based on local investigator's assessment according to RECIST v1.1. According to this criteria, CR = at least two determinations of CR at least 4 weeks apart before progression; PR = at least two determinations of PR or better at least 4 weeks apart before progression (and not qualifying for a CR). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) 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.
Duration of Response (Phase Lll) every 8 weeks after randomization Up to 3 months after end of Treatment time from the date of the first documented response (CR or PR, which had to be confirmed subsequently) to the date of the first radiologically documented disease progression or death due to disease
Time to Response (Phase Lll) every 8 weeks after randomization Up to 3 months after end of Treatment time from date of randomization until first documented response (CR or PR, which has to be confirmed subsequently).
Clinical Benefit Rate (CBR) (Phase ll) every 8 weeks after randomization Up to 3 months after end of Treatment CBR was defined as the percentage of patients with an overall response of CR or PR or SD or non-CR/non-PD lasting more than 24 weeks based on local Investigator's assessment according to RECIST v1.1.
Plasma Concentration-time Profiles of BKM120 - Pharmacokinetics (PK) (Phase Lll) Cycle 1 day 1, 15, 16, 22 and Cycle 2 day 1. Summary statistics for PK: plasma concentration-time profiles of BKM120 and appropriate individual PK parameters based on population PK model , if deemed appropriate; each cycle = 28 days
Time to Definitive Deterioration of ECOG Performance Status (Phase Lll) every 4 weeks Time to definitive deterioration of the ECOG performance status from baseline
Trial Locations
- Locations (22)
Baylor Health Care System/Sammons Cancer Center Baylor Texas Oncology
🇺🇸Dallas, Texas, United States
University of Texas Southwestern Medical Center Harry Hines
🇺🇸Dallas, Texas, United States
Cancer Care Centers of South Texas / HOAST CCC of So. TX- San Antonio
🇺🇸San Antonio, Texas, United States
Arizona Oncology Associates Dept of Oncology
🇺🇸Phoenix, Arizona, United States
Rocky Mountain Cancer Centers RMCC Hale Pkwy
🇺🇸Greenwood Village, Colorado, United States
Ironwood Cancer and Research Centers SC
🇺🇸Chandler, Arizona, United States
Novartis Investigative Site
🇬🇧Wirral, United Kingdom
Northwest Georgia Oncology Center NW Georgia Onc
🇺🇸Marietta, Georgia, United States
Norton Healthcare, Inc.
🇺🇸Louisville, Kentucky, United States
California Cancer Care Marian Speciality
🇺🇸Greenbrae, California, United States
H. Lee Moffitt Cancer Center & Research Institute SC
🇺🇸Tampa, Florida, United States
Emory University School of Medicine/Winship Cancer Institute Dept.of WinshipCancerInst. (2)
🇺🇸Atlanta, Georgia, United States
University of Nebraska Medical Center Unv Nebraska Med Ctr (2)
🇺🇸Omaha, Nebraska, United States
University of Kansas Cancer Center Univ Kansas 2
🇺🇸Kansas City, Kansas, United States
Washington University School of Medicine Regulatory
🇺🇸St. Louis, Missouri, United States
New York Oncology Hematology, P.C. Dept. of New York Oncology. PC
🇺🇸Troy, New York, United States
Medical Oncology & Hematology Associates of Northern VA Med Onc Hem Northern VA
🇺🇸Reston, Virginia, United States
Highlands Oncology Group Dept of Highlands Oncology Grp
🇺🇸Fayetteville, Arkansas, United States
University of New Mexico Cancer Research Center Dept of Univ New Mexico
🇺🇸Albuquerque, New Mexico, United States
Northwest Cancer Specialists Vancouver Loc
🇺🇸Portland, Oregon, United States
Ohio State Comprehensive Cancer Center/James Cancer Hospital SC-1
🇺🇸Columbus, Ohio, United States
University of Oklahoma Health Sciences Center OUHSC 2
🇺🇸Oklahoma City, Oklahoma, United States