AzTrials
AzTrials

Breast NeoplasmsPhase 2NCT01953445

Paclitaxel and BKM120 Before Surgery in Treating Patients With Stage II or III Estrogen Receptor-Positive and HER2-Negative Breast Cancer

A Phase 2 study testing paclitaxel and BKM120 in people with Breast Neoplasms, run by Washington University School of Medicine.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial summary

This phase II trial studies the effects of paclitaxel combined with phosphoinositide 3-kinase (PI3K) inhibitor BKM120 in patients with stage II or III breast cancer that is described as estrogen receptor-positive, human epidermal growth factor 2 (HER2)-negative and endocrine therapy resistant. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Neoplasms
What is being tested?
paclitaxel and BKM120
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Aug 2014to Jul 2015
Phase
Phase 2
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

  • Clinical stage II or III ER-positive, HER2-negative breast cancer with complete surgical excision of the breast cancer as the treatment goal.
  • Tumor size at least 2cm in one dimension by clinical or radiographic examination (WHO criteria).
  • Received at least 2 weeks of neoadjuvant endocrine therapy.
  • Ki67 after 2 to 12 weeks of neoadjuvant endocrine therapy is > 10% confirmed by central testing at Washington University.
  • At least 18 years of age.
  • ECOG performance status ≤ 2
Show all 17Show fewer
  • Normal bone marrow and organ function as defined below:
  • Absolute neutrophil count ≥ 1,500/mcl
  • Platelets ≥ 100,000/mcl
  • Hemoglobin > 9.0 g/dL
  • AST(SGOT)/ALT(SGPT) <= IULN
  • Serum bilirubin within normal limits (OR total bilirubin ≤ 3.0 x IULN with direct bilirubin within normal range in patients with well documented Gilbert Syndrome)
  • Creatinine ≤ 1.5 x IULN OR Creatinine clearance ≥ 50 mL/min/1.73 m2
  • plasma glucose ≤ 120 mg/dL (6.7 mmol/L)
  • Patient may be pre- or post-menopausal. Women of childbearing potential must agree to use adequate contraception prior to study entry, for the duration of study participation, and for up to 30 days following completion of treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
  • Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
  • Because breast cancer occurs predominantly in women, men will not be eligible for this trial. Women and members of all races and ethnic groups are eligible for this trial.

Who cannot join

  • Prior therapy with a PI3K inhibitor for the indexed breast cancer.
  • Sentinel lymph node dissection prior to neoadjuvant therapy.
  • Currently receiving any other investigational agents.
  • Acute or chronic liver disease, renal disease, or pancreatitis.
  • A history of allergic reactions attributed to compounds of similar chemical or biologic composition to BKM120 or paclitaxel or other agents used in the study.
  • Presence of one of the following mood disorders (as judged by the physician or a psychiatrist or as a result of the patient's mood assessment questionnaire):
Show all 35Show fewer
  • Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, or a history of suicidal attempt/ideation or homicidal ideation (immediate risk of doing harm to others) or patients with active severe personality disorders (defined according to DSM- IV) are not eligible. Note: for patients with psychotropic treatments ongoing at baseline, the dose and the schedule should not be modified within the previous 6 weeks prior to start of study drug.
  • ≥ CTCAE grade 3 anxiety
  • Meets the cut-off score of ≥ 12 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 in the PHQ-9 (independent of the total score of the PHQ-9)
  • CTCAE grade 2 diarrhea.
  • Presence of active cardiac disease, including any of the following:
  • Left ventricular ejection fraction (LVEF) < 50% as determined by MUGA or echocardiogram
  • QTC > 480 msec on screening ECG (using the QTcF formula)
  • Angina pectoris that requires the use of anti-anginal medication
  • Ventricular arrhythmias except for benign premature ventricular contractions
  • Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication
  • Conduction abnormality requiring a pacemaker
  • Valvular disease with document compromise in cardiac function
  • Symptomatic pericarditis.
  • History of cardiac dysfunction including any of the following:
  • Myocardial infarction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities of LVEF function
  • History of documented congestive heart failure (New York Heart Association function classification III-IV)
  • Documented cardiomyopathy.
  • Poorly controlled diabetes mellitus or steroid-induced diabetes mellitus.
  • Significant symptomatic deterioration of lung function. If clinically indicated, pulmonary function tests including measures of predicted lung volumes, DLco, O2 and/or saturation at rest on room air should be considered to exclude pneumonitis or pulmonary infiltrates.
  • 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.
  • Impairment of gastrointestinal function or GI disease that may significantly alter the absorption of BKM120 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
  • Treatment with hematopoietic colon-stimulating growth factors (e.g., G-CSF, GM-CSF) within the 2 weeks prior to starting study drug. Erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to enrollment, may be continued.
  • Currently receiving treatment with medication which carries a known risk of prolonging QT interval or inducing Torsades de Pointes. If treatment with this drug can be discontinued and the patient can be switched to a different medication prior to starting study drug, this is acceptable.
  • Receiving chronic treatment with steroid or another immunosuppressive agent. Note that topical applications, inhaled sprays, eye drops, or local injections are allowed.
  • Consumption of known CYP3A inhibitors such as Seville oranges, grapefruit, pummelos, exotic citrus fruits, St. John's wort, Kava, ephedra (ma huang), gingko biloba), dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng.
  • Currently receiving treatment with medication known to be a moderate or strong inhibitor or inducer of isoenzyme CYP3A. If treatment with this drug can be discontinued and the patient can be switched to a different medication prior to starting study drug, this is acceptable. Please note that concomitant treatment with a weak inhibitor of CYP3A is allowed.
  • Currently taking therapeutic doses of warfarin sodium or any other Coumadin-derivative anticoagulant.
  • Pregnant and/or breastfeeding. Patient must have a negative serum pregnancy test within 72 hours of starting treatment.
  • Known HIV-positivity.

About this study

Official title: Neoadjuvant Phase II Trial of Paclitaxel in Combination With BKM120 in Endocrine Resistant Clinical Stage II or III Estrogen Receptor-Positive and HER2 Negative Breast Cancer

This phase II trial studies the effects of paclitaxel combined with phosphoinositide 3-kinase (PI3K) inhibitor BKM120 in patients with stage II or III breast cancer that is described as estrogen receptor-positive, human epidermal growth factor 2 (HER2)-negative and endocrine therapy resistant. Drugs such as paclitaxel stop the growth of tumors by blocking cancer cell division. PI3K inhibitor BKM120 inhibits some of the enzymes needed for cell growth and may improve the response of endocrine resistant tumors to treatment. Giving paclitaxel and PI3K inhibitor BKM120 before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Being tested
paclitaxel, BKM120
Medical subject headings
Breast Neoplasms

What participants receive

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

  • paclitaxelDrug

    Also called Anzatax, Asotax, Bristaxol, Praxel, TAX, Taxol, Taxol Konzentrat

  • BKM120Drug

Study groups in NCT01953445
Study groupRoleWhat they receive
Treatment (PI3K inhibitor BKM120, paclitaxel)ExperimentalPatients receive PI3K inhibitor BKM120 PO QD on days 1-28 and paclitaxel IV over 60 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.
Receives: Drug: paclitaxel; Drug: BKM120

What is being measured

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

  1. Pathologic complete response rate in patients with endocrine therapy resistant tumors following neoadjuvant paclitaxel in combination with BKM120

    Proportion of patients with no histologic evidence of invasive tumor cells in the surgical breast specimen and axillary or lymph nodes. A 90% confidence interval for the pCR rate will be constructed using the Duffy-Santner approach.

    Measured: After 2-12 weeks on neoadjuvant endocrine therapy

Secondary outcomes (2)

  1. Proportion of patients who developed severe (grade 3+) toxicity related to neoadjuvant treatment

    Assessed using the National Cancer Institute (NCI)-CTCAE version 4.0.

    Measured: Up to 30 days after completion of study treatment

  2. Clinical response rate in patients with endocrine therapy resistant tumors following neoadjuvant paclitaxel in combination with BKM120

    Proportion of eligible patients whose disease burden meets the WHO criteria for complete or partial response before surgery. A 95% binomial confidence interval for the clinical response rate will be constructed.

    Measured: Up to 12 weeks

Timeline

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

  1. First posted1 Oct 2013 (estimated)
  2. Study startAug 2014
  3. Primary completionJun 2015 (estimated)
  4. Study completionJul 2015 (estimated)

Why it stopped: The study sponsor found the trial to be not viable.

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
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01953445
Sponsor's protocol ID
201311126
Status last verified
Dec 2014
First submitted
19 Sep 2013
Last updated
8 Dec 2014
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing paclitaxel and BKM120 in people with Breast Neoplasms, run by Washington University School of Medicine.

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 17 inclusion and 35 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: withdrawn, as of the sponsor's last update on 8 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.

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?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 was withdrawn before enrolling participants, so there are no results.

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?

Pathologic complete response rate in patients with endocrine therapy resistant tumors following neoadjuvant paclitaxel in combination with BKM120 (time frame: After 2-12 weeks on neoadjuvant endocrine therapy). 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 NCT01953445.

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 8 Dec 2014.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in