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Metastatic Breast CancerPhase 1/2NCT01132664

Phase 1b/2 Study of BKM120 Plus Trastuzumab in Patients With HER2-positive Breast Cancer

A Phase 1/2 study testing BKM120, Trastuzumab and Capecitabine in people with Metastatic Breast Cancer and HER2+ Breast Cancer, run by Novartis Pharmaceuticals at 21 sites in 6 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This study will assess the safety and efficacy of BKM120 in combination with trastuzumab in patients with relapsing HER2 overexpressing breast cancer who have previously failed trastuzumab. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Breast Cancer, HER2+ Breast Cancer
What is being tested?
BKM120, Trastuzumab and Capecitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
72 participants
Where
21 sitesin 6 countries
Study dates
May 2010to Aug 2014
Phase
Phase 1/2
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
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • World Health Organization (WHO) Performance Status of ≤ 2
  • Patients with HER2+ breast cancer by local laboratory testing (immunohistochemistry [IHC] 3+ staining or fluorescence in situ hybridization [FISH] confirmation for IHC 2+ and 1+)
  • Documented tumor resistance to trastuzumab:
  • Recurrence while on trastuzumab or within 12 months since the last infusion for patients who received trastuzumab as adjuvant treatment
  • Progression while on or within 4 weeks since the last infusion of trastuzumab for patients who received trastuzumab for metastatic disease.
  • Documented evidence of progressive disease per Response Evaluation Criteria in Solid Tumors (RECIST) on trastuzumab-based therapy defined as:
Show all 33Show fewer
  • Phase Ib: at any time before study entry
  • Phase II: within 16 weeks before date of first dosing
  • Received at least 1 but no more than 4 prior anit-HER2 based regimens including at least 1 regimen containing trastuzumab (adjuvant or neo-adjuvant trastuzumab will be considered as one prior regimen). HER2 directed therapies are defined as comprising trastuzumab, lapatinib, and trastuzumab-DM1 (T-DM1) only.
  • Phase II only: trastuzumab, T-DM1 or lapatinib must be part of the most recent line of therapy
  • Previous lines of cytotoxic chemotherapy:
  • Phase Ib: no more than 4 lines of cytotoxic chemotherapy
  • Phase II: no more than 3 lines of cytotoxic chemotherapy
  • Measurable disease:
  • Phase Ib: patient has at least one measurable lesion or non-measurable disease as defined per RECIST
  • Phase II: patient has at least one measureable lesion as defined per RECIST
  • || Specific Inclusion Criteria for patients in BM cohorts:
  • Patient has evidence of progressing brain metastases and/or new metastatic brain lesion(s) without leptomeningeal disease.
  • Patient has received prior WBRT and/or SRS at at >28 and >/= 14 days, respectively, prior to starting study drug and the patient must have recovered from the side effects of the therapy
  • WHO performance status of </=1
  • PT INR </= 1.5
  • Any number of prior HER2-directed and cytotoxic regimens, and the most recent line may be any type of anti-neoplastic therapy
  • || Exclusion Criteria:
  • Patients with untreated brain metastases
  • Patients with acute or chronic liver, renal disease or pancreatitis
  • Patients with any peripheral neuropathy ≥ Common Terminology Criteria for Adverse Events (CTCAE) grade 2
  • Patients with a history of mood disorders or ≥ CTCAE grade 3 anxiety
  • Patient with clinical manifest diabetes mellitus or steroid-induced diabetes mellitus
  • || Specific Exclusion Criteria for patients in BM cohorts
  • Prior treatment with capecitabine
  • Patient has known dihydropyrimidine dehydrogenase (DPD) deficiency
  • Patient is currently receiving treatment with EIAED
  • Other protocol-defined inclusion/exclusion criteria may apply

Who cannot join

None listed.

Trial locations and contacts

21 sites in 6 countries.

21 sites in 6 countries

United States7 sites

  • University of Alabama at Birmingham/ Kirklin Clinic Univ AL - PI

    Birmingham, Alabama, 35294-0006

  • Karmanos Cancer Institute Dept.of KarmanosCancerInst (6)

    Detroit, Michigan, 48201

  • Highlands Oncology Group Dept of Highlands Oncology Grp

    Fayetteville, Arkansas, 72703

  • Sarah Cannon Research Institute Sarah Cannon Cancer Center SC

    Nashville, Tennessee, 37203

  • Beth Israel Medical Center BIMC

    New York, New York, 10003

  • Washington University School Of Medicine-Siteman Cancer Ctr WA Siteman

    St Louis, Missouri, 63110

  • H. Lee Moffitt Cancer Center & Research Institute

    Tampa, Florida, 33612

Other trials in United States

Italy4 sites

  • Novartis Investigative Site

    Cagliari, CA, 09134

  • Novartis Investigative Site

    Modena, MO, 41100

  • Novartis Investigative Site

    Province of Macerata, MC, 62100

  • Novartis Investigative Site

    Terni, TR, 05100

Other trials in Italy

Spain3 sites

  • Novartis Investigative Site

    Barcelona, Catalonia, 08035

  • Novartis Investigative Site

    L'Hospitalet de Llobregat, Catalonia, 08907

  • Novartis Investigative Site

    Valencia, Valencia, 46010

Other trials in Spain

United Kingdom3 sites

  • Novartis Investigative Site

    Brighton, East Sussex, BN2 5BE

  • Novartis Investigative Site

    Nottingham, NG5 1PB

  • Novartis Investigative Site

    Oxford, OX3 7LJ

Other trials in United Kingdom

Belgium2 sites

  • Novartis Investigative Site

    Liège, 4000

  • Novartis Investigative Site

    Wilrijk, 2610

Other trials in Belgium

France2 sites

  • Novartis Investigative Site

    Lyon, 69373

  • Novartis Investigative Site

    Saint-Herblain Cédex, 44805

Other trials in France

About this study

Official title: A Phase Ib/II, Open Label, Multi-center Study Evaluating the Safety and Efficacy of BKM120 in Combination With Trastuzumab in Patients With Relapsing HER2 Overexpressing Breast Cancer Who Have Previously Failed Trastuzumab

This study will assess the safety and efficacy of BKM120 in combination with trastuzumab in patients with relapsing HER2 overexpressing breast cancer who have previously failed trastuzumab.

The study will further assess the safety and preliminary efficacy of BKM120 in combination with trastuzumab and capecitabine in patients with relapsing HER2 overexpressing breast cancer and brain metastases (BM) who have previously failed trastuzumab.

Being tested
BKM120, Trastuzumab, Capecitabine
Keywords
HER2, BKM120, PIK3, metastatic breast cancer, brain metastases, Herceptin, trastuzumab, capecitabine, open-label, maximum tolerated dose, Phase I/Phase ll
Medical subject headings
Breast Neoplasms, Brain Neoplasms

What participants receive

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

  • BKM120Drug

    Buparlisib (BKM120) is the investigational drug. Burparlisib was supplied as 10 mg and 50 mg hard gelatin capsules. Buparlisib was dosed on a flat scale of mg/day and not adjusted to body weight or body surface area. Buparlisib capsules were packaged in high density polyethylene bottles with a plastic child resistant closure.

  • TrastuzumabDrug

    Trastuzumab was used in this study according to the local regulations in each participating country. A loading dose (4 mg/kg) of trastuzumab was administered (if required as assessed by the principal Investigator based on the timing of the last trastuzumab dose prior to enrollment) on Day -7 over 90 minutes, followed by weekly intravenous infusion of 2 mg/kg maintenance doses from Day 1 of Cycle 1 (over 30 minutes if the previous infusion was well tolerated).

  • CapecitabineDrug

    1000 mg/m2 twice a day from day 1 to Day 14 of a 21-day cycle.

Study groups in NCT01132664
Study groupRoleWhat they receive
HER2+ metastatic breast cancerExperimentalPatients with HER2-overexpressing metastatic breast cancer, with or without PIK3 signaling pathway alteration, who have previously failed trastuzumab
Receives: Drug: BKM120; Drug: Trastuzumab
HER2+ metastatic breast cancer with BMExperimentalPatients with HER2-overexpressing metastatic breast cancer and brain metastases, with or without PIK3 signaling pathway alteration, who have previously failed trastuzumab
Receives: Drug: BKM120; Drug: Trastuzumab; Drug: Capecitabine

What is being measured

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

  1. Dose Limiting Toxicity (DLT) - Phase l Only

    Determination of the maximum tolerated dose (MTD) in the dose escalation part of the study was based upon the estimation of the probability of DLT in Cycle 1 in patients of the dose-determining set.

    Measured: cycle 1 - 28 days

  2. Overall Response Rate (ORR) - Phase ll

    Objective response rate (ORR) was defined as the rate of patients with best overall response (BOR) equal to complete response (CR) or partial response (PR) according to RECIST 1.0 from the Investigators review.

    Per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0 assessed of the disease status by imaging (i.e. CT/MRI): Complete Response (CR) = Disappearance of all tumor lesions; Partial Response (PR)= >=30% shrinkage of lesions; Overall Response (OR) = patients with CR and PR.

    Measured: 18 months

Secondary outcomes (3)

  1. Disease Control Rate (DCR) Based on Investigator Assessment- Phase l & ll

    Disease control rate (DCR) = patients with complete response (CR), partial response (PR) or stable disease (SD) as per RECIST criteria.

    Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0 assessed the disease status by imaging (i.e. CT/MRI): CR = disappearance of all tumor lesions; PR = >=30% shrinkage of lesions; SD = Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease (PD); PD = At least a 20% increase in the sum of the longest diameter of all measured target lesions, taking as reference the smallest sum of longest diameter of all target lesions recorded at or after baseline.

    Measured: 18 months

  2. Clinical Benefit Rate (CBR) - Phase l & ll

    CBR = patients with CR, PR or SD ≥ 24 weeks according to RECIST by the investigator.

    Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0 assessed the disease status by imaging (i.e. CT/MRI): CR = Disappearance of all tumor lesions; PR= >=30% shrinkage of lesions; SD = Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD; PD = At least a 20% increase in the sum of the longest diameter of all measured target lesions, taking as reference the smallest sum of longest diameter of all target lesions recorded at or after baseline.

    Measured: 18 months

  3. Progression Free Survival (PFS) - Based on Investigator Review Using Kaplan Meier - Phase l & ll

    Measured: 18 months

Timeline

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

  1. First posted28 May 2010 (estimated)
  2. Study startMay 2010
  3. Primary completionAug 2014
  4. Study completionAug 2014

Why it stopped: Due to the rare patient population and challenges to enroll patients.

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
72 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01132664
Sponsor's protocol ID
CBKM120X2107
Other IDs
2009-015417-46, 2009
Status last verified
Aug 2016
First submitted
7 May 2010
Last updated
17 Aug 2016
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing BKM120, Trastuzumab and Capecitabine in people with Metastatic Breast Cancer and HER2+ Breast Cancer, run by Novartis Pharmaceuticals at 21 sites in 6 countries.

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 33 inclusion and 0 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: stopped early, as of the sponsor's last update on 17 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in United States, Italy, Spain, United Kingdom, Belgium and 1 more country. 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 combined 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.

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 30 Oct 2015). 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?

Dose Limiting Toxicity (DLT) - Phase l Only (time frame: cycle 1 - 28 days). The study lists 2 primary outcomes in all. 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 NCT01132664.

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 17 Aug 2016.

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