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Breast CancerEarly Phase 1NCT01513356

Pharmacodynamic Study of BKM120 in Breast Cancer

A Early Phase 1 study testing BKM120 in people with Breast Cancer, run by Sofia Perea, Director Clinical Trials Unit. at 1 site in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

BKM120 is a potent and highly specific oral pan-class I phosphatidylinositol-3-kinase (PI3K) inhibitor, currently under investigation in a first-in-man study in patients with advanced solid tumors (wild type and PIK3CA-mutated). Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
BKM120
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteSpain
Study dates
Oct 2012to Feb 2014
Phase
Early Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age ≥ 18 years
  • ER+ / HER2 negative breast cancer patients
  • WHO performance status £ 2
  • Previously untreated histologically confirmed invasive, non-metastatic, breast carcinoma with a tumor size ≥ 1,5cm and non urgent surgical treatment
  • Activated Pi3K pathway in breast cancer trucut biopsy
  • Documentation of negative pregnancy test for patients of child bearing potential within 7 days prior to start study treatment. Sexually active pre-menopausal patients must use adequate contraceptive measures, excluding estrogen containing contraceptives, while on study.
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  • Patients must meet the following laboratory criteria within 7 days prior to start the study treatment:
  • Hematology
  • Neutrophil count of > 1200/mm3
  • Platelet count of > 100,000/ mm3
  • Hemoglobin > 90g/L
  • Biochemistry
  • AST/SGOT and ALT/SGPT < 2.5 x upper limit of normal (ULN) or < 5.0 x ULN if the transaminase elevation is due to liver metastases
  • Total bilirubin < 1.5 x ULN [Patients with Gilbert Syndrome must have total bilirubin < 3 ULN]
  • Cholesterol < ULN - 7.75 mmol/L and Triglycerides < ULN - 2.5 x ULN (with lipid-lowering drugs permitted)
  • Serum creatinine < 1.5 x ULN or 24-hour creatinine clearance > 60 mL/min
  • Serum albumin > LLN or > 30 g/L
  • Fasting plasma glucose ≤ 140 mg/dL (7.8 mmol/L)

Who cannot join

  • Patients who have received prior treatment with a P13K inhibitor
  • Patients with a known hypersensitivity to BKM120 or to its excipients
  • Patients with a history of photosensitivity reactions to other drugs
  • Patients with the following mood disorders as judged by the Investigator or a psychiatrist, or as result of patient's mood assessment questionnaire:
  • 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)
  • ≥ CTCAE grade 3 anxiety The psychiatric judgment overrules the mood assessment questionnaire result/investigators judgment.
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  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKM120 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection). Patients with unresolved diarrhea will be excluded as previously indicated
  • Patients with diabetes mellitus requiring insulin treatment, history of gestational diabetes mellitus
  • Impaired cardiac function or clinically significant cardiac diseases
  • LVEF < 45% as determined by MUGA scan or ECHO
  • Complete left bundle branch block
  • ST depression or elevation of ≥ 1.5 mm in 2 or more leads
  • Congenital long QT syndrome
  • History or presence of ventricular arrhythmias or atrial fibrillation
  • Clinically significant resting bradycardia (< 50 beats per minute)
  • QTc > 460 msec on screening ECG
  • Right bundle branch block + left anterior hemiblock (bifascicular block)
  • Unstable angina pectoris ≤ 3 months prior to starting the study drug
  • Acute myocardial infarction ≤ 3 months prior to starting the study drug
  • Other clinically significant heart disease such as congestive heart failure requiring treatment or uncontrolled hypertension
  • Patients who have been treated with any hematopoietic colony-stimulating growth factors (e.g., G-CSF, GM-CSF) ≤ 2 weeks prior to starting study drug. Erythropoietin or darbepoetin therapy, if initiated before enrollment, may be continued
  • Patients who are currently receiving treatment with medication that has the potential to prolong the QT interval or inducing Torsades de Pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug
  • Patients who are currently receiving treatment with therapeutic doses of warfarin sodium (Coumadin®)
  • Patients with known coagulopathies
  • Patients who have received chemotherapy, immunotherapy (except for trastuzumab) or investigational drugs ≤ 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy
  • Patients who have received any continuous-dosing (i.e. daily dosing, ever-other-day dosing, Monday-Wednesday-Friday dosing weekly etc) therapeutic modalities or investigational drug (excluding monoclonal antibodies) ≤ 5 half lives prior to starting study drug or who have not recovered from side effects of such therapy
  • Patients who have received corticosteroids ≤ 2 weeks prior to starting study drug or who have not recovered from the side effects of corticosteroid treatment
  • Patients who have received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy.
  • Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
  • Women of child-bearing potential who are pregnant or breast feeding and adults of reproductive potential not employing an effective method of birth control. Adequate contraception must be used throughout the trial and for 8 weeks after the last dose of study drug, by both sexes. Women of child-bearing potential must have a negative serum pregnancy test ≤ 7 days prior to starting BKM120
  • Male patients whose sexual partner(s) are WOCBP who are not willing to use adequate contraception, during the study and for 8 weeks after the end of treatment
  • Patients with a known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory)
  • Patients with a history of another primary malignancy that is currently clinically significant, has potential for metastases or currently requires active intervention
  • Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
  • Patients with any other concurrent severe and/or uncontrolled concomitant medical conditions (e.g. active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol
  • History of noncompliance to medical regimens
  • Patients unwilling to or unable to comply with the protocol

Trial locations and contacts

1 site in 1 country.

Spain1 site

  • Hospital Madrid Norte Sanchinarro- CIOCC

    Madrid, Madrid, 28050

Other trials in Spain

About this study

Official title: Evaluation of PI3K/AKT/mTOR Signaling Pathway Using BKM120 in Early Breast Cancer

BKM120 is a potent and highly specific oral pan-class I phosphatidylinositol-3-kinase (PI3K) inhibitor, currently under investigation in a first-in-man study in patients with advanced solid tumors (wild type and PIK3CA-mutated). Consistent, dose-dependent pharmacodynamic activity has been demonstrated and clear signs of anti-tumor activity have been seen with BKM120.

Read the detailed description

BKM120 is a potent and highly specific oral pan-class I phosphatidylinositol-3-kinase (PI3K) inhibitor, currently under investigation in a first-in-man study in patients with advanced solid tumors (wild type and PIK3CA-mutated). Consistent, dose-dependent pharmacodynamic activity has been demonstrated and clear signs of anti-tumor activity have been seen with BKM120. Three breast cancer patients showed significant tumor shrinkage after ≥ 2 months. Two confirmed partial responses (PRs) per RECIST have been seen, one in a patient with a triple negative KRAS-mutated breast cancer and the other in a patient with an estrogen receptor (ER)-positive, PIK3CAmutated tumor. Two minor responses have also been observed; one of these occurred in a HER2+/ER+ breast cancer patient.

Conditions
Breast Cancer
Being tested
BKM120
Keywords
breast, cancer, BKM120
Medical subject headings
Breast Neoplasms, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BKM120Drug

    BKM120 will be administered on a continuous once daily dosing schedule at a dose of 100 mg (p.o.)until progression of disease or unacceptable toxicity or a maximum of 4 weeks.

Study groups in NCT01513356
Study groupRoleWhat they receive
CBKM120ExperimentalBKM120 will be administered on a continuous once daily dosing schedule at a dose of 100 mg (p.o.)during 28 days
Receives: Drug: BKM120

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. - To determine the grade of inhibition of PI3K/mTOR pathways, in pre-surgery setting with BKM120

    Biomarkers assessments must be performed at baseline and at the end of study treatment. The following biomarkers will be assessed: PI3K, KRAS, pAkt and -RPS6p

    Measured: 28 days

Secondary outcomes (2)

  1. Number, grade and relationship of adverse events with BKM120

    Measured: 28 days

  2. Potential predictive biomarkers (PI3K mutation, KRAS, pAkt and RPS6p) for a pathologic complete response relating to BKM120

    Measured: 28 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Jan 2012 (estimated)
  2. Study startOct 2012
  3. Primary completionFeb 2014
  4. Study completionFeb 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01513356
Sponsor's protocol ID
CBKM120XES01T
Status last verified
Apr 2014
First submitted
21 Dec 2011
Last updated
2 Apr 2014
Results posted
No
Data monitoring committee
No

Publications

  • Bendell JC, Rodon J, Burris HA, de Jonge M, Verweij J, Birle D, Demanse D, De Buck SS, Ru QC, Peters M, Goldbrunner M, Baselga J. Phase I, dose-escalation study of BKM120, an oral pan-Class I PI3K inhibitor, in patients with advanced solid tumors. J Clin Oncol. 2012 Jan 20;30(3):282-90. doi: 10.1200/JCO.2011.36.1360. Epub 2011 Dec 12.

    PubMed 22162589

  • Park E, Park J, Han SW, Im SA, Kim TY, Oh DY, Bang YJ. NVP-BKM120, a novel PI3K inhibitor, shows synergism with a STAT3 inhibitor in human gastric cancer cells harboring KRAS mutations. Int J Oncol. 2012 Apr;40(4):1259-66. doi: 10.3892/ijo.2011.1290. Epub 2011 Dec 8.

    PubMed 22159814

  • Koul D, Fu J, Shen R, LaFortune TA, Wang S, Tiao N, Kim YW, Liu JL, Ramnarian D, Yuan Y, Garcia-Echevrria C, Maira SM, Yung WK. Antitumor activity of NVP-BKM120--a selective pan class I PI3 kinase inhibitor showed differential forms of cell death based on p53 status of glioma cells. Clin Cancer Res. 2012 Jan 1;18(1):184-95. doi: 10.1158/1078-0432.CCR-11-1558. Epub 2011 Nov 7.

    PubMed 22065080

  • Maira SM. PI3K inhibitors for cancer treatment: five years of preclinical and clinical research after BEZ235. Mol Cancer Ther. 2011 Nov;10(11):2016. doi: 10.1158/1535-7163.MCT-11-0792. No abstract available.

    PubMed 22072802

  • Leung E, Kim JE, Rewcastle GW, Finlay GJ, Baguley BC. Comparison of the effects of the PI3K/mTOR inhibitors NVP-BEZ235 and GSK2126458 on tamoxifen-resistant breast cancer cells. Cancer Biol Ther. 2011 Jun 1;11(11):938-46. doi: 10.4161/cbt.11.11.15527. Epub 2011 Jun 1.

    PubMed 21464613

  • Brunner-Kubath C, Shabbir W, Saferding V, Wagner R, Singer CF, Valent P, Berger W, Marian B, Zielinski CC, Grusch M, Grunt TW. The PI3 kinase/mTOR blocker NVP-BEZ235 overrides resistance against irreversible ErbB inhibitors in breast cancer cells. Breast Cancer Res Treat. 2011 Sep;129(2):387-400. doi: 10.1007/s10549-010-1232-1. Epub 2010 Nov 3.

    PubMed 21046231

  • Brachmann SM, Hofmann I, Schnell C, Fritsch C, Wee S, Lane H, Wang S, Garcia-Echeverria C, Maira SM. Specific apoptosis induction by the dual PI3K/mTor inhibitor NVP-BEZ235 in HER2 amplified and PIK3CA mutant breast cancer cells. Proc Natl Acad Sci U S A. 2009 Dec 29;106(52):22299-304. doi: 10.1073/pnas.0905152106. Epub 2009 Dec 10.

    PubMed 20007781

  • Maira SM, Stauffer F, Brueggen J, Furet P, Schnell C, Fritsch C, Brachmann S, Chene P, De Pover A, Schoemaker K, Fabbro D, Gabriel D, Simonen M, Murphy L, Finan P, Sellers W, Garcia-Echeverria C. Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity. Mol Cancer Ther. 2008 Jul;7(7):1851-63. doi: 10.1158/1535-7163.MCT-08-0017. Epub 2008 Jul 7.

    PubMed 18606717

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing BKM120 in people with Breast Cancer, run by Sofia Perea, Director Clinical Trials Unit. at 1 site in Spain.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

- To determine the grade of inhibition of PI3K/mTOR pathways, in pre-surgery setting with BKM120 (time frame: 28 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01513356, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2014.

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