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A Trial of BKM120 (a PI3K Inhibitor) in Patients With Triple Negative Metastatic Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01629615
Recruitment Status : Completed
First Posted : June 27, 2012
Last Update Posted : April 19, 2018
Novartis Pharmaceuticals
Dana-Farber Cancer Institute
Stand Up To Cancer
Information provided by (Responsible Party):
SOLTI Breast Cancer Research Group

Brief Summary:
The purpose of this study is to evaluate the clinical activity of BKM120 in patients with metastatic triple-negative breast cancer.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: BKM120 Phase 2

Detailed Description:

This is a prospective, non-randomized, open-label, multicenter, single-arm exploratory study of single agent BKM120 in the treatment of metastatic triple negative breast cancer patients.

Patients will first undergo screening, tumor measurement and collection of available tumor block from the primary tumor and/or a metastatic site. Available tumor block is required in all patients per inclusion criteria. Analysis of this tumor block will be used for correlation of predictive markers and clinical response in order to define potential subpopulation that benefit from BKM120.

Following confirmation of eligibility criteria, subjects will be enrolled. BKM120 will then be administered in a 100mg dose, orally, once daily, in a continuous schedule. A treatment cycle is defined as 28 days for the purposes of scheduling procedures and evaluations.

Treatment with BKM120 will continue until disease progression, unacceptable toxicity that precludes any further treatment, and/or discontinuation of the treatment by investigator or patient decision.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Trial of BKM120 (a PI3K Inhibitor) in Patients With Triple Negative Metastatic Breast Cancer
Study Start Date : June 2012
Actual Primary Completion Date : October 2015
Actual Study Completion Date : October 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: BKM120 Drug: BKM120
BKM120 oral capsules. 100 mg daily in cycles of 28 days, until disease progression

Primary Outcome Measures :
  1. Rate of clinical benefit = CR + PR + SD for ≥4 months per RECIST 1.1 [ Time Frame: Rate of clinical benefit for at least 4 months ]

Secondary Outcome Measures :
  1. Progression-free survival [ Time Frame: Every 8 weeks from study entry to up to 2 years ]
  2. Overall survival [ Time Frame: 2 years ]
    From recruiting date until death by any cause.

  3. Frequency and severity of adverse events [ Time Frame: Continuous, until 30 days after treatment stops ]
  4. Molecular alterations in tumor tissue that correlate with clinical activity of BKM120 [ Time Frame: 2 years ]
  5. Change from baseline in expression levels of p-AKT and S6 in tumors [ Time Frame: At day 28 of cycle 1 ]
  6. Change from baseline in glucose metabolism markers [ Time Frame: At day 28 of cycle 1 ]
  7. Rate of clinical benefit = CR + PR + SD for >=4 months per RECIST 1.1 after preselection [ Time Frame: Rate of clinical benefit for at least 4 months ]
    To determine if preselection of patients depending on specific tumor molecular alterations can increase the probability of a clinical response to BKM120

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Pathologically and radiologically confirmed metastatic TNBC (Stage IV disease), previously documented by histological analysis, which is ER-negative and PR-negative by IHC and HER2 negative by IHC or FISH/CISH.
  • Subjects must have received maximum two prior chemotherapy regimens for metastatic breast cancer.
  • Availability of a representative tumor specimen (primary or metastasis, archival tissue or fresh biopsy for patients with biopsiable tumor) at baseline.
  • At least one measurable lesion by RECIST 1.1
  • Age ≥ 18 years at the day of consenting to the study
  • ECOG performance status ≤ 2
  • Adequate bone marrow and organ function as defined by the following laboratory values: ANC ≥ 1.0 x 109/L, platelets ≥ 100 x 109/L, hemoglobin ≥ 9.0 g/dL, INR ≤ 2; serum potassium between 3.0mmol/L and 5.5 mmol/L; Corrected serum calcium between8.0mg/dL and 11.5mg/dL (OR between 1.0mmol/L and 1.5mmol/L of Ionized calcium); serum magnesium between 1.2mg/dL and 3.0 mg/dL; serum creatinine ≤ 1.5 x ULN, ALT and AST within normal range (or ≤ 3.0 x ULN if liver metastases are present); serum bilirubin within normal range (or ≤ 1.5 x ULN if liver metastases are present; or total bilirubin ≤ 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert Syndrome); fasting plasma glucose (FPG) ≤ 140 mg/dL or ≤ 7.8 mmol/L.

Exclusion Criteria:

  • Previous treatment with PI3K inhibitors
  • Symptomatic CNS metastases
  • Patients with controlled and asymptomatic CNS metastases may participate in this trial. As such, the patient must have completed any prior treatment for CNS metastases > 28 days (including radiotherapy and/or surgery) prior to enrollment in this study. Patients with previously treated brain metastases, who are on a stable low dose corticosteroids treatment are eligible
  • Concurrent malignancy or malignancy within 3 years of study enrollment (with the exception of adequately treated basal or squamous cell carcinoma or non-melanomatous skin cancer). An exception to this rule are those patients with documented germline mutations in BRCA1 or 2, who may have previous history of cancer
  • Any of the following mood disorders as judged by the Investigator or a Psychiatrist, or meets the cut-off score of ≥ 10 in the PHQ-9 or a cut-off of ≥ 15 in the GAD-7 mood scale, respectively, or selects a positive response of '1, 2, or 3' to question number 9 regarding potential for suicidal thoughts ideation in the PHQ-9 (independent of the total score of the PHQ-9)

    1. Patients with a history or active episodes of major depression, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, history of suicide attempts or suicidal thoughts (eg. Risk of hurting or harming others) or patients with severe personality disorders (as defined by the DSM-IV) are not eligible. Note: For patients who are treated with psychotropic drugs at baseline, the dose and schedule shall not be changed during the 6 weeks prior to initiation of treatment with the study drug.
    2. ≥ CTCAE v 4.0 grade 3 anxiety
  • Patients on concurrent use of other approved or investigational antineoplastic and / or chemotherapy or any continuous or intermittent treatment with therapeutic agents of low molecular weight (excluding monoclonal antibodies) in ≤ 21 days prior to enrollment in this study or who have not recovered from the effects such therapy will not be eligible.
  • Radiotherapy ≤ 28 days prior to enrollment in this study or failure to recover from side effects of such therapy at the time of initiation of screening procedures.
  • Major surgery within 28 days prior to starting study drug or has not recovered from major side effects of the surgery
  • Poorly controlled diabetes mellitus (HbA1c > 8%)
  • Active cardiac disease including any of the following:

    1. Left Ventricular Ejection Fraction (LVEF) < 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO)Note: ECHO/MUGA is only required at baseline if patient has a history of abnormal cardiac test results
    2. QTc > 480 msec on screening ECG (using the QTcF formula
    3. Angina pectoris that requires the use of anti-anginal medication
    4. Ventricular arrhythmias except for benign premature ventricular contractions
    5. Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication
    6. Conduction abnormality requiring a pacemaker
    7. Valvular disease with documented compromise in cardiac function
    8. Symptomatic pericarditis
  • History of cardiac dysfunction including any of the following;

    1. Myocardial infarction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function
    2. History of documented congestive heart failure (New York Heart Association functional classification III-IV)
    3. Documented cardiomyopathy
  • Treatment with QT prolonging medication known to have a risk to induce Torsades de Pointes, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKM120 (e.g., uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
  • Chronic treatment with steroids or another immunosuppressive agent. Note: Topical applications (e.g., rash), inhaled sprays (e.g., obstructive airways diseases), eye drops or local injections (e.g., intra-articular) are allowed. Patients with previously treated brain metastases, who are on a stable low dose corticosteroids treatment (e.g., dexamethasone 2 mg/day, prednisone 10 mg/day) for at least 14 days before start of study treatment, are eligible
  • Other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment contraindicate her participation in the clinical study (e.g., chronic pancreatitis, active chronic hepatitis etc.)
  • History of non-compliance to medical regimen
  • Current treatment with drugs known to be moderate and strong inhibitors or inducers of isoenzyme CYP3A, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug
  • Known history of HIV (testing not mandatory) infection
  • Pregnant or nursing (lactating) woman
  • Woman of child-bearing potential unwilling to observe total sexual abstinence or to use a double barrier method for birth control throughout the trial. Reliable contraception should be maintained throughout the study and for 6 months after study drug discontinuation

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01629615

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United States, Massachusetts
Dana-Farber at Faulkner Hospital
Boston, Massachusetts, United States, 02130
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Hospital Universitario Vall d´Hebron
Barcelona, Spain, 08035
Hospital Universitario 12 de Octubre
Madrid, Spain, 28041
Instituto Valenciano de Oncología
Valencia, Spain, 46009
Hospital Clínico Universitario de Valencia
Valencia, Spain, 46010
Sponsors and Collaborators
SOLTI Breast Cancer Research Group
Novartis Pharmaceuticals
Dana-Farber Cancer Institute
Stand Up To Cancer
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Study Chair: Jose Baselga, MD Massachusetts General Hospital
Study Chair: Eric Winer, MD Dana-Farber Cancer Institute
Principal Investigator: Jordi Rodon, MD Hospital Universitario Vall d´Hebron
Additional Information:
Saura C, Lin N, Ciruelos E, Lluch A, Gavilá J, Winer E, Baselga J, Rodón J. A phase II, non-randomized, multicenter, exploratory trial of single agent BKM120 in patients with triple-negative metastatic breast cancer. Poster session presented at: 35th Annual San Antonio Breast Cancer Symposium (SABCS); 2012 December 4th-8th; San Antonio, Texas, United States.

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Responsible Party: SOLTI Breast Cancer Research Group Identifier: NCT01629615    
Other Study ID Numbers: CBKM120ZES02T/SOLTI-1103
2011-006083-45 ( EudraCT Number )
First Posted: June 27, 2012    Key Record Dates
Last Update Posted: April 19, 2018
Last Verified: July 2015
Keywords provided by SOLTI Breast Cancer Research Group:
breast cancer
triple negative breast cancer
PI3K inhibitor
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases