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Metastatic Breast CancerPhase 1NCT01248494

PhIb BKM120 or BEZ235+Endocrine Treatment in Post-Menopausal Patients With Hormone Receptor + Metastatic Breast Cancer

A Phase 1 study testing BEZ235, BKM 120 and Letrozole in people with Metastatic Breast Cancer, run by Vanderbilt-Ingram Cancer Center at 6 sites 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 an open-label phase Ib multi-institution trial that evaluates the safety profile/tolerability and preliminary anti-tumor effect of BKM120 (a PI3K inhibitor) and endocrine therapy combination and BEZ235 (a PI3K/ mTOR inhibitor) and endocrine therapy combination in postmenopausal patients with hormone… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Breast Cancer
What is being tested?
BEZ235, BKM 120 and Letrozole
Could I receive a placebo?
No, everyone receives an active treatment
How many people
72 participants
Where
6 sitesUnited States
Study dates
Nov 2010to May 2016
Phase
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
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must provide informed written consent.
  • Patients must be >/= 18 years of age.
  • ECOG performance status 0-1.
  • Clinical stage IV invasive mammary carcinoma, ER-positive and/or PR-positive by immunohistochemistry (IHC). Patients may have either measurable or nonmeasurable disease, both are allowed.
  • Patients whose breast cancers are also HER2-overexpressed (IHC 3+ or FISHpositive)need to have had previous treatment exposure to trastuzumab (Herceptin®)
  • Prior endocrine therapy (any) is allowed. There is not limit on lines of prior treatment in the metastatic setting.
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  • Patients must have available tissue (archived formalin-fixed paraffin embedded blocks (FFPB) or fresh frozen tissue from original diagnosis or metastatic setting) for correlative studies. Tissue needs to be submitted at the time of registration. Patients will not be able to start study drugs without tissue availability.
  • Life expectancy >/= 6 months
  • Patients must have adequate hematologic, hepatic, and renal function. All tests must be obtained less than 4 weeks from study entry. This includes:
  • ANC >/= 1500/mm3
  • Platelet count >/= 100,000/mm3
  • HgB >/= 9 g/dL
  • Creatinine </= 1.5X upper limits of normal
  • INR </= 2Total serum bilirubin </= 1.5 x ULN (in patients with known Gilbert Syndrome, a total bilirubin </= 3.0 x ULN, with direct bilirubin </= 1.5 x ULN)
  • AST and ALT </= 3 x ULN (or </= 5.0 x ULN if hepatic metastases are present)
  • Fasting plasma glucose (FPG) </= 140 mg/dL [7.8 mmol/L]. For patients with known diabetes, HgBA1c needs to be </= 8%
  • Patients must be able to swallow and retain oral medication.
  • Post-menopausal female subjects should be defined prior to protocol enrollment by any of the following:
  • Subjects at least 55 years of age
  • Subjects under 55 years of age and amenorrheic for at least 12 months or follicle-stimulating hormone (FSH) values >/= 40 IU/L and estradiol levels </= 20 IU/L;
  • Prior bilateral oophorectomy
  • Prior radiation castration with amenorrhea for at least 6 months
  • Current use of an LHRH agonist for more than 12 months
  • Patients may have received radiation therapy to painful bone metastases or areas of impending bone fracture as long as radiation therapy is completed >/= 2 weeks prior to study entry. Patients who have received prior radiotherapy must have recovered from toxicity (</= grade 1) induced by this treatment
  • Patients must be disease-free of prior invasive cancers for > 5 years with the exception of basal or squamous cancer of the skin or cervical carcinoma in situ.
  • Patients must complete all screening assessments as outlined in the protocol.

Who cannot join

  • Locally recurrent resectable breast cancer.
  • Any kind of malabsorption syndrome significantly affecting gastrointestinal function.
  • Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, hormonal therapy, biologic therapy) other than the ones specified in the protocol. Patients must have discontinued the above cancer therapies for 1 week prior to the first dose of study medication, as well as recovered from toxicity (to </= than grade 1, except for alopecia) induced by previous treatments. Any investigational drugs should be discontinued 2 weeks prior to the first dose of study medication.
  • Prior therapy with a PI3K specific inhibitor. Prior use of Akt or mTOR inhibitors are allowed.
  • Use of any of the drugs (prohibited concomitant medications)
  • Patients with the following mood disorders as judged by the Investigator or a psychiatrist:
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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)
  • >/= CTCAE grade 3 anxiety
  • 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 in the PHQ-9 (independent of the total score of the PHQ-9) will be excluded from the study unless overruled by the psychiatric assessment
  • Uncontrolled intercurrent illness including, but not limited to:
  • ongoing or active infection requiring parenteral antibiotics
  • impairment of lung function (COPD > grade 2, lung conditions requiring oxygen therapy)
  • symptomatic congestive heart failure (class III or IV of the New York Heart Association classification for heart disease)
  • Left Ventricular Ejection Fraction (LVEF) < 50%
  • unstable angina pectoris, angioplasty, stenting, or myocardial infarction within 6 months
  • uncontrolled hypertension (systolic blood pressure >160 mm Hg or diastolic blood pressure > 100 mm Hg, found on two consecutive measurements separated by a 1 or 2-week period despite adequate medical support)
  • clinically significant cardiac arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia that is symptomatic or requires treatment [National Cancer Institute -Common Terminology Criteria for Adverse Events, Version 4.0, grade 3]
  • QTcF >/= 480 msec on screening EKG
  • known history of QT/QTc prolongation or Torsades de Pointes (TdP)
  • ST depression or elevation of ≥ 1.5 mm in 2 or more leads
  • Diarrhea of any cause >/= CTCAE grade 2
  • psychiatric illness/social situations that would compromise patient safety or limit compliance with study requirements including maintenance of a compliance/pill diary
  • patients with symptomatic brain metastases (patients with a history of brain metastases must be clinically stable for more than 4 weeks from completion of radiation treatment and 4 weeks from steroid tapering)
  • patients with known history of chronic liver or renal failure
  • patients with known history of chronic pancreatitis

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites

  • University of Alabama

    Birmingham, Alabama

  • Massachusetts General Hospital, Dana Farber Cancer Center

    Boston, Massachusetts, 02114

  • Vanderbilt Cool Springs

    Nashville, Tennessee, 37067

  • Vanderbilt Breast Center One Hundred Oaks

    Nashville, Tennessee, 37204

  • Vanderbilt-Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Columbia University Medical Center

    New York, New York

Other trials in United States

About this study

Official title: A Phase Ib Trial of BKM120 (a PI3K Inhibitor) or BEZ235 (a PI3K/mTOR Inhibitor) in Combination With Endocrine Therapy in Post-Menopausal Patients With Hormone Receptor-Positive Metastatic Breast Cancer

This is an open-label phase Ib multi-institution trial that evaluates the safety profile/tolerability and preliminary anti-tumor effect of BKM120 (a PI3K inhibitor) and endocrine therapy combination and BEZ235 (a PI3K/ mTOR inhibitor) and endocrine therapy combination in postmenopausal patients with hormone receptor-positive metastatic breast cancer.

Being tested
BEZ235, BKM 120, Letrozole, 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.

  • BEZ235Drug

    • Dose level 1: 400mg PO BID
    • Dose level -1: 400mg PO in AM and 200mg PO in PM
    • Dose level -2: 200mg PO BID

  • BKM 120Drug

    • Dose Level 1: BKM120, 100 mg PO daily
    • Dose level -1: BKM120, 80 mg PO daily
    • Dose Level -2: BKM120, 60 mg PO daily

  • LetrozoleDrug

    All levels: 2.5mg/day PO

  • BKM120Drug

    • Dose Level 1: BKM120, 100 mg PO from Mondays through Fridays, weekly
    • Dose level -1: BKM120, 80 mg PO from Mondays through Fridays, weekly
    • Dose Level -2: BKM120, 60 mg PO from Mondays through Fridays, weekly
Study groups in NCT01248494
Study groupRoleWhat they receive
BEZ235 + LetrozoleExperimentalNot described
Receives: Drug: BEZ235; Drug: Letrozole
BKM120 + LetrozoleExperimentalNot described
Receives: Drug: BKM 120; Drug: Letrozole
Intermittent BKM120 + LetrozoleExperimentalNot described
Receives: Drug: Letrozole; Drug: BKM120

What is being measured

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

  1. Maximum Tolerated Dose of BKM120 or BEZ235 given in combination with endocrine therapy

    The maximum tolerated dose for each of the arms will be defined as the highest dose tested in which a DLT is experienced by 0 out of 3 or 1 out of 6 patients among the dose levels. The first cohort of patients (3 patients) in each arm will be started at dose level 1, and each patient will be observed for 4 weeks on the specified dose.

    Measured: at 4 weeks

Secondary outcomes (2)

  1. Number of Patients with Progression-free survival (PFS)

    The overall PFS data will be estimated using the Kaplan-Meier method with the 95% confidence interval. The Cox proportional hazards model will be applied to investigate potential prognostic factors, such as disease free interval after completion of adjuvant endocrine therapy on the time to event data. The adjusted p-values as well as the adjusted 95% confidence intervals from the Cox model will be reported.

    Measured: 4 weeks after off-treatment date

  2. Response Rate (RR)

    All of the patients who met the eligibility criteria (with the possible exception of those who received no study medication) should be included in the main analysis of the response rate.

    Measured: 4 weeks after off-treament date

Timeline

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

  1. First posted25 Nov 2010 (estimated)
  2. Study startNov 2010
  3. Primary completionDec 2012
  4. Study completionMay 2016

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 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
72 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01248494
Sponsor's protocol ID
VICC BRE 1055
Status last verified
Jul 2016
First submitted
23 Nov 2010
Last updated
25 Jul 2016
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BEZ235, BKM 120 and Letrozole in people with Metastatic Breast Cancer, run by Vanderbilt-Ingram Cancer Center at 6 sites 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 26 inclusion and 25 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 25 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

Maximum Tolerated Dose of BKM120 or BEZ235 given in combination with endocrine therapy (time frame: at 4 weeks). 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 NCT01248494.

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 25 Jul 2016.

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