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Brain MetastasesPhase 2NCT02000882

STAR Cape+BKM120 MBC With Brain Met

A Phase 2 study testing BKM120, capecitabine and Trastuzumab in people with Brain Metastases and Breast Cancer, run by US Oncology Research at 1 site in United States.

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

This is a study to determine the safety and effectiveness of BKM120 plus capecitabine in breast cancer patients with brain metastases. Both capecitabine and BMK120 have previously shown activity in patients with breast cancer. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
BKM120, capecitabine and Trastuzumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
1 siteUnited States
Study dates
29 May 2014to 29 Mar 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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
  • Female
  • Histologically and/or cytologically confirmed diagnosis of inoperable metastatic breast cancer
  • ER+/HER2- OR HER2+ OR triple-negative breast cancer, assessed as ER-, PgR-, and HER2-negative by local laboratory testing; HER2 negative status (based on most recently analyzed biopsy) is defined as IHC status of 0, 1+ or 2+ (if IHC 2+, a negative FISH test is required, ie, HER2 FISH ratio < 2.0); ER-negative and PR-negative status is defined as ER and PgR <10% nuclei positive by IHC. HER2-positive status is defined as 3+ staining in ≥10% of cells by immunohistochemistry or a HER2/CEP17 ratio ≥2 or an average of ≥6 HER2 gene copies per cell by in situ hybridization (ISH)
  • At least one CNS lesion that is at least 5mm in size in at least one dimension in the setting of prior WBRT
  • Prior WBRT is required and may have been administered at any time in patient's treatment history. Patients in the primary analysis will not have evidence of progression of disease following WBRT. However, patients whose brain metastases have progressed following WBRT are eligible. Patients must have completed WBRT at least 3 weeks prior to study entry.
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  • Prior SRS is allowed, but previous treatment of the 5mm target CNS lesion with SRS is not permitted
  • ECOG performance status ≤ 2
  • Adequate bone marrow function as shown by: ANC ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L, Hb >9 g/dL
  • Total calcium (corrected for serum albumin) within normal limits (biphosphonate use for malignant hypercalcemia control is not allowed)
  • Magnesium ≥ the lower limit of normal
  • Potassium within normal limits for the institution
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range (or ≤ 3.0 x upper limit of normal (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 known Gilbert Syndrome)
  • Serum creatinine ≤ 1.5 x ULN or 24-hour clearance ≥ 50 mL/min
  • Serum amylase ≤ ULN
  • Serum lipase ≤ ULN
  • Fasting plasma glucose ≤ 120 mg/dL (6.7 mmol/L)
  • Negative serum pregnancy test within 72 hours before starting study treatment in women with childbearing potential
  • INR ≤ 2
  • Life expectancy > 12 weeks
  • Available tissue (blocks and/or slides) samples unless discussed in advance with study principal investigator
  • Patient is able to swallow and retain oral medication
  • Signed most recent patient informed consent form
  • Signed Patient Authorization Form

Who cannot join

  • Patient received prior treatment with a P13K inhibitor.
  • Patient with known hypersensitivity to BKM120, capecitabine, or their excipients.
  • Patient has evidence of impending herniation on baseline brain imaging.
  • Patient has evidence of diffuse leptomeningeal disease on brain MRI or by previously documented CSF.
  • Patient has acute or chronic liver, renal disease or pancreatitis (liver metastases are allowed)
  • Patients has a mood disorder as judged by the Investigator or a psychiatrist, or as a result of patient's mood assessment questionnaire (PHQ-9 and/or GAD-7):
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  • 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) 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)
  • Patients has diarrhea ≥ CTCAE grade 2
  • Patients with uncontrolled hypertension defined as systolic blood pressure 170 or greater or diastolic blood pressure over 100.
  • Patient has active cardiac disease including any of the following:
  • Left ventricular ejection fraction (LVEF) < 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO)
  • 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
  • Patient has a 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 on assessment of LVEF function
  • History of documented congestive heart failure (New York Heart Association functional classification III-IV)
  • Documented cardiomyopathy
  • Patient has poorly controlled diabetes mellitus or steroid-induced diabetes mellitus
  • Patient has 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
  • Significant symptomatic deterioration of lung function. If clinically indicated, pulmonary function tests including measures of predicted lung volumes, DLco, O2 saturation at rest on room air should be considered to exclude pneumonitis or pulmonary infiltrates.
  • 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
  • Patient was 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 at least 2 weeks prior to enrollment, may be continued
  • Patient is currently receiving treatment with medication with a known risk 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 receiving chronic treatment with steroids or another immunosuppressive agent. Patients must have been off all corticosteroids (except for physiologic doses of hydrocortisone as replacement therapy) for at least 2 weeks prior to study entry.
  • Note: Single doses, or topical applications (e.g. rash), inhaled sprays (e.g. obstructive airways diseases), eye drops or local injections (e.g. intra-articular) are allowed.
  • Patient has taken herbal medications and certain fruits within 7 days prior to starting study drug. Herbal medications include, but are not limited to St. John's wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng. Fruits include the CYP3A inhibitors Seville oranges, grapefruit, pummelos, or exotic citrus fruits. Regular orange juice is permitted.
  • Patient is currently treated 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. Please refer to Table 4-8 for a list of prohibited inhibitors and inducers of CYP3A (Please note that co-treatment with weak inhibitors of CYP3A is allowed).
  • Patient received chemotherapy or targeted anticancer therapy ≤ 3 weeks (6 weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug, and have related side effects must recover to a grade 1 or less before starting the trial
  • Patient received any continuous or intermittent small molecule therapeutics (excluding monoclonal antibodies) with ≤ 5 effective half lives prior to starting study drug or who have not recovered from side effects of such therapy
  • Patient 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
  • Patient underwent major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy.
  • Patient is currently taking therapeutic doses of warfarin sodium or any other coumadin-derivative anticoagulant.
  • Patient is pregnant or breast feeding or is of reproductive potential and not employing an effective method of birth control.
  • Note: Double barrier contraceptives must be used through the trial by both sexes. Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study. Women of child-bearing potential, defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months), must have a negative serum pregnancy test ≤ 72 hours prior to initiating treatment.
  • Note: Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL [for US only: and estradiol < 20 pg/mL] or have had surgical bilateral oophorectomy (with or without hysterectomy) at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.
  • Note: Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use highly effective contraception during treatment for 4 weeks (5 T1/2) after stopping treatment. The highly effective contraception is defined as either:
  • True abstinence: When this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
  • Sterilization: have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.
  • Male partner sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate). For female subjects on the study, the vasectomised male partner should be the sole partner for that patient.
  • Use of a combination of any two of the following (a+b):
  • Placement of an intrauterine device (IUD) or intrauterine system (IUS)
  • Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository
  • Oral contraception, injected or implanted hormonal methods are not allowed as BKM120 potentially decreases the effectiveness of hormonal contraceptives.
  • Patient has known diagnosis of human immunodeficiency virus (HIV) infection
  • Patient has history of another malignancy within 5 years, except cured basal cell carcinoma of the skin or excised carcinoma in situ of the cervix
  • Patient is unable or unwilling to abide by the study protocol or cooperate fully with the investigator
  • Patient is concurrently using other approved or investigational antineoplastic agent.
  • Patient taking or needing enzyme-inducing anti-epileptic medication.
  • Patient has an acute viral hepatitis or a history of chronic or active HBV or HCV infection

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Please contact Zuzanne Bristow for list of sites

    Multiple Locations, Texas

Other trials in United States

About this study

Official title: Phase II Multicenter Single-arm Study of BKM120 Plus Capecitabine for Breast Cancer Patients With Brain Metastases

This is a study to determine the safety and effectiveness of BKM120 plus capecitabine in breast cancer patients with brain metastases.

Both capecitabine and BMK120 have previously shown activity in patients with breast cancer. Like capecitabine, BMK120 is also effective in crossing the blood brain barrier making it a preferred candidate for its evaluation in patients with metastatic breast cancer (MBC).

Read the detailed description

This is a Phase 2, multicenter, single-arm study to determine the safety and efficacy of BKM120 plus capecitabine in breast cancer patients with brain metastases. 40 patients will be included, who have either ER+/HER2-, HER2+ or triple negative breast cancer..

The Graded Prognostic Assessment (GPA) is a recently developed, validated prognostic score for patients with brain metastases. The Graded Prognostic Assessment will be utilized to evaluate efficacy in this clinical study.

Capecitabine is a prodrug which is enzymatically converted to 5-fluorouracil in its tumor target where it inhibits DNA synthesis and slows tumor growth. It is currently FDA approved for both colorectal and breast cancer. BMK120 is a pan phosphatidylinositol-3-kinase inhibitor being developed under IND# 102,823 by Novartis Corporation. As of September 2012 over 600 patients had been enrolled in fourteen separate Novartis sponsored monotherapy or combination therapy clinical studies of BMK120.

Phosphatidylinositol-3-kinase (PI3K) signaling regulates diverse cellular functions including cell proliferation, survival, translational regulation of protein synthesis, glucose metabolism, cell migration, and angiogenesis. PI3K signaling also serves a central role in the pathogenesis of numerous cancers.

Constitutive activation of PI3K signaling is known to be a critical step in mediating the transforming potential of oncogenes and tumor suppressors in many tumor types. Resistance to a variety of therapeutic interventions, including hormonal therapy, anti-HER2 therapies and chemotherapy can also be linked to constitutive activation of the PI3K pathway.

Preliminary data suggest that activation of the PI3K pathway is a predictor of a poor prognostic outcome in many cancer types. Thus, as a pan-PI3K inhibitor, BMK120 may provide a therapeutic benefit to patients with MBC. Both capecitabine and BMK120 have previously shown activity in patients with MBC. Like capecitabine, BMK120 is also effective in crossing the blood brain barrier making it a preferred candidate for its evaluation in patients with MBC.

Trastuzumab is a monoclonal antibody that targets the HER2 receptor which is overexpressed or amplified in approximately 20-25% of breast cancers. The clinical benefit of trastuzumab in women with metastatic breast cancer has been demonstrated in two pivotal studies.

Current clinical experience with BMK120 has shown that its most frequent adverse events (AEs) include fatigue, decreased appetite, diarrhea, hyperglycemia, nausea, rash and mood alteration disorders. Therefore patients will be closely monitored for fasting plasma glucose (FPG) HbA1c, and insulin C-peptide. Patients will also be frequently and routinely evaluated for mood disorders and disturbances. The remaining most frequent AEs will be detected by regular, frequent monitoring with symptomatic treatment to be provided as required.

Being tested
BKM120, capecitabine, Trastuzumab
Keywords
Breast Cancer, Triple Negative Breast Cancer, Brain Metastases, Capecitabine, Metastatic Breast Cancer
Medical subject headings
Brain Neoplasms, Breast Neoplasms, Triple Negative Breast Neoplasms

What participants receive

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

Study groups in NCT02000882
Study groupRoleWhat they receive
BKM120 plus CapecitabineExperimentalBKM120 will be administered at a dose of 100 mg orally (PO) daily. Capecitabine will be administered at a dose of 1000 mg/m2 orally (PO) twice a day (rounded down to the nearest 500 mg pill) 14 days on and 7 days off. For patients with HER2+ MBC only, standard every 3-weekly trastuzumab (6 mg/kg IV) will be added to the capecitabine/BKM120.
Receives: Drug: BKM120; Drug: capecitabine; Drug: Trastuzumab

What is being measured

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

  1. Clinical Benefit Rate (CBR)

    CBR in the patients following WBRT or SRS or both will be the primary endpoint and is calculated as the total number of responders (CR or PR, assessed by RECIST 1.1) plus stable disease greater than or equal to 24 weeks (CR + PR + SD ≥ 24 weeks) divided by the total number of evaluable patients.

    Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.

    Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

    Measured: until disease progression (assessed by RECIST 1.1), unacceptable toxicity, death, or discontinuation from study for any other reason, up to 2 years from date of patient registration

Secondary outcomes (4)

  1. Objective Response Rate (ORR)

    To assess ORR (CR + PR) associated with BKM120 plus capecitabine in the central nervous system based on local investigator assessment. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.

    Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

    Measured: until disease progression (assessed by RECIST 1.1), unacceptable toxicity, death, or discontinuation from study for any other reason, up to 2 years from date of patient registration

  2. Median Time to Progression

    To assess median time to progression (TTP) associated with BKM120 plus capecitabine.

    Measured: until disease progression (assessed by RECIST 1.1), unacceptable toxicity, death, or discontinuation from study for any other reason, up to 2 years from date of patient registration

  3. Median Overall Survival

    To determine median overall survival (OS) associated with BKM120 plus capecitabine.

    Measured: up to 2 years from date of patient registration

  4. Number of Treatment-related Serious AEs

    To characterize the safety and tolerability of BKM120 plus capecitabine, with or without trastuzumab

    Measured: until disease progression (assessed by RECIST 1.1), unacceptable toxicity, death, or discontinuation from study for any other reason, up to 2 years from date of patient registration

Timeline

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

  1. First posted4 Dec 2013 (estimated)
  2. Study start29 May 2014
  3. Primary completion29 Mar 2019
  4. Study completion29 Mar 2019

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
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02000882
Sponsor's protocol ID
11025
Other IDs
CBKM120ZUS39T
Status last verified
Jan 2022
First submitted
26 Nov 2013
Last updated
7 Feb 2022
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing BKM120, capecitabine and Trastuzumab in people with Brain Metastases and Breast Cancer, run by US Oncology Research at 1 site in United States.

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 25 inclusion and 56 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 7 Feb 2022. 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 United States. 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?

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?

Yes. Results are posted in the registry (first posted 1 Feb 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Clinical Benefit Rate (CBR) (time frame: until disease progression (assessed by RECIST 1.1), unacceptable toxicity, death, or discontinuation from study for any other reason, up to 2 years from date of patient registration). 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 NCT02000882.

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 7 Feb 2022.

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