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

This study is currently recruiting participants.
Verified September 2013 by SOLTI Breast Cancer Research Group
Sponsor:
Collaborators:
Novartis Pharmaceuticals
Dana-Farber Cancer Institute
Stand Up To Cancer
Information provided by (Responsible Party):
SOLTI Breast Cancer Research Group
ClinicalTrials.gov Identifier:
NCT01629615
First received: May 23, 2012
Last updated: September 27, 2013
Last verified: September 2013
  Purpose

The purpose of this study is to evaluate the clinical activity of BKM120 in patients with metastatic triple-negative breast cancer who have developed disease progression after standard chemotherapy in the adjuvant or metastatic settings.


Condition Intervention Phase
Breast Cancer
Drug: BKM120
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of BKM120 (a PI3K Inhibitor) in Patients With Triple Negative Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by SOLTI Breast Cancer Research Group:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: Every 8 weeks from study entry to up to 2 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    From recruiting date until death by any cause.

  • Frequency and severity of adverse events [ Time Frame: Continuous, until 30 days after treatment stops ] [ Designated as safety issue: Yes ]
  • Molecular alterations in tumor tissue that correlate with clinical activity of BKM120 [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Change from baseline in expression levels of p-AKT and S6 in tumors [ Time Frame: At day 28 of cycle 1 ] [ Designated as safety issue: No ]
  • Change from baseline in glucose metabolism markers [ Time Frame: At day 28 of cycle 1 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
    To determine if preselection of patients depending on specific tumor molecular alterations can increase the probability of a clinical response to BKM120


Estimated Enrollment: 50
Study Start Date: June 2012
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BKM120 Drug: BKM120
BKM120 oral capsules. 100 mg daily in cycles of 28 days, until disease progression

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 that have progressed to at least 2 lines of chemotherapy in the neoadjuvant, adjuvant, or metastatic setting.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 at least two prior neoadjuvant chemotherapy regimens, adjuvant or metastatic
  • 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. Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others)
    2. ≥ CTCAE v 4.0 grade 3 anxiety
  • Concurrent use of other approved or investigational antineoplastic agent and/or chemotherapy ≤ 21 days prior to enrollment in this study.
  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01629615

Contacts
Contact: Josefa Morales, PhD +34 93 343 63 02 morales.pepi@gruposolti.org

Locations
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Nancy Lin, MD       nancy_lin@dfci.harvard.edu   
Contact: Catherine Zeghibe       catherine_zeghibe@dfci.harvard.edu   
Principal Investigator: Nancy Lin, MD         
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Gerburg Wulf, MD, PhD       Gwulf@bidmc.harvard.edu   
Contact       breastresearch@bidmc.harvard.edu   
Principal Investigator: Gerburg Wulf, MD, PhD         
Dana-Farber at Faulkner Hospital Recruiting
Boston, Massachusetts, United States, 02130
Contact: Eric Mayer, MD, MPH       eric_mayer@dfci.harvard.edu   
Contact: Kimberly Washington       kwashington3@partners.org   
Principal Investigator: Eric Mayer, MD, MPH         
Spain
Hospital Universitario Vall d´Hebron Recruiting
Barcelona, Spain, 08035
Contact: Susana Muñoz       smunoz@vhio.net   
Principal Investigator: Cristina Saura, MD         
Hospital Universitario 12 de Octubre Recruiting
Madrid, Spain, 28041
Contact: Olga Ortega       oortega@h12o.es   
Contact: Maria José Aguilella       mjose.aguilela@salud.madrid.org   
Principal Investigator: Eva Ciruelos, MD         
Instituto Valenciano de Oncología Recruiting
Valencia, Spain, 46009
Contact: Laura Calabuig       coordinacion@fincivo.org   
Principal Investigator: Joaquin Gavila, MD         
Hospital Clínico Universitario de Valencia Recruiting
Valencia, Spain, 46010
Contact: Estela Contel       contel_est@gva.es   
Principal Investigator: Ana Lluch, MD         
Sponsors and Collaborators
SOLTI Breast Cancer Research Group
Novartis Pharmaceuticals
Dana-Farber Cancer Institute
Stand Up To Cancer
Investigators
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
  More Information

Additional Information:
No publications provided

Responsible Party: SOLTI Breast Cancer Research Group
ClinicalTrials.gov Identifier: NCT01629615     History of Changes
Other Study ID Numbers: CBKM120ZES02T/SOLTI-1103, 2011-006083-45
Study First Received: May 23, 2012
Last Updated: September 27, 2013
Health Authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by SOLTI Breast Cancer Research Group:
breast cancer
metastatic
triple negative breast cancer
BKM120
SOLTI
PI3K inhibitor

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases

ClinicalTrials.gov processed this record on April 16, 2014