Inoperable Locally Advanced Breast CancerPhase 1/2NCT01495247

Phase Ib/II Trial of BEZ235 With Paclitaxel in Patients With HER2 Negative, Locally Advanced or Metastatic Breast Cancer

A Phase 1/2 study testing BEZ235 and Paclitaxel in people with Inoperable Locally Advanced Breast Cancer and Metastatic Breast Cancer (MBC), run by Novartis Pharmaceuticals at 3 sites in 2 countries.

Terminated

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

Official record

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Trial summary

Who is it for?: Ages 18 years and older, women only
Conditions the study is for: Inoperable Locally Advanced Breast Cancer, Metastatic Breast Cancer (MBC)
What is being tested?: BEZ235 and Paclitaxel
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 18 participants
Where: 3 sitesin 2 countries
Study dates: 30 Jan 2012to 19 May 2014
Phase: Phase 1/2
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

Females with Breast cancer that is histologically or cytologically confirmed, HER2 negative and locally advanced or metastatic as confirmed by radiology
ECOG performance status 0 and 1
Adequate bone marrow and organ function

Who cannot join

Previous treatment with PI3K and/or mTOR inhibitors
Symptomatic Central Nervous System (CNS) metastases
Concurrent malignancy or malignancy in the last 5 years prior to start of study treatment
Wide field radiotherapy ≤ 28 days or limited field radiation for palliation ≤ 14 days prior to starting study drug
Active cardiac disease (e.g. LVEF less than institutional lower limit of normal, QTcF > 480 msec, unstable angina pectoris, ventricular, supraventricular or nodal arrhythmias)
Inadequately controlled hypertension

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Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BEZ235 and/or paclitaxel
Treatment at start of study treatment with drugs with a known risk to induce Torsades de Pointes, moderate and strong inhibitors or inducers of isoenzyme CYP3A4, warfarin and coumadin analogues, LHRH agonists
Sensitivity to paclitaxel treatment
Uncontrolled diabetes mellitus
Pregnant or nursing (lactating) woman
Other protocol-defined inclusion/exclusion criteria may apply

Trial locations and contacts

3 sites in 2 countries.

Country

City, postcode or hospital

3 sites in 2 countries

France2 sites

Novartis Investigative Site
Dijon, 21034
Novartis Investigative Site
Saint-Herblain Cédex, 44805

Other trials in France

Spain1 site

Novartis Investigative Site
L'Hospitalet de Llobregat, Catalonia, 08907

Other trials in Spain

About this study

Official title: A Dose-finding Phase Ib Study Followed by an Open-label, Randomized Phase II Study of BEZ235 Plus Paclitaxel in Patients With HER2 Negative, Inoperable Locally Advanced or Metastatic Breast Cancer

This is a prospective, multi-center, open-label, phase Ib/ II study (two parts) with patients that have locally advanced or metastatic HER2 negative breast cancer. The first part (phase Ib) will investigate the MTD / Recommended Phase 2 Dose (RP2D) of the combination therapy of BEZ235 twice daily (b.i.d.) and weekly paclitaxel using a Bayesian model. When MTD/ RP2D is established the second part (phase II) will start. Phase II will evaluate the efficacy and the safety of weekly paclitaxel alone compared to weekly paclitaxel plus BEZ235 bid.

Conditions: Inoperable Locally Advanced Breast Cancer, Metastatic Breast Cancer (MBC)
Being tested: BEZ235, Paclitaxel
Keywords: Locally advanced, metastatic, breast cancer, HER2 negative, PI3K pathway, paclitaxel, mTOR inhibitor
Medical subject headings: Breast Neoplasms, Neoplasm Metastasis

What participants receive

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

BEZ235Drug
Doses of oral BEZ235 (BID), supplied as 50mg, 200mg, 300mg or 400mg in SDS sachets, together with standard weekly paclitaxel at a fixed dose (80mg/m²) during 1h by i.v. in infusion.
PaclitaxelDrug
The paclitaxel infusion will be given in the morning and directly thereafter the BEZ235 dose will be given.
BEZ235 doses will be escalated in cohorts of 3 to 6 patients guided by an adaptive Bayesian logistic regression model with overdose control until MTD/RP2D has been established. The initial dose level for the first cohort will be 200mg (BID), and then based on the Bayesian model the dose may be escalated to 300mg, 400mg, 500mg or 600mg for the next cohorts.

Study groups in NCT01495247
Study group	Role	What they receive
BEZ235 100 mg bid + paclitaxel 80 mg (phase lb)	Experimental	Increasing doses of oral BEZ235 100 mg administered on a continuous twice daily (BID) schedule + weekly paclitaxel infusion at a fixed dose of 80 mg/m2. Treatment was organized into cycles of 28 days. Receives: Drug: BEZ235; Drug: Paclitaxel
BEZ235 200 mg bid + paclitaxel 80 mg (phase lb)	Experimental	Increasing doses of oral BEZ235 200 mg administered on a continuous twice daily (BID) schedule + weekly paclitaxel infusion at a fixed dose of 80 mg/m2. Treatment was organized into cycles of 28 days Receives: Drug: BEZ235; Drug: Paclitaxel

What is being measured

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

Phase lb: Dose Limiting Toxicities (DLTs) the first cycle of treatment
DLT is defined as treatment-related toxicity (classified according Common Toxicity Criteria for Adverse Events (CTCAE) Version 4) occurring during the first 28 treatment days and meeting specific protocol-predefined criteria.
The information will be integrated in a Bayesian logistic regression model with overdose control to estimate the maximum tolerated dose (MTD).
Measured: At first treatment intake (Cycle 1 Day 1 = C1D1), C1D8, C1D15, C1D22 and C2D1 [a cycle = 4 weeks = 28 days]

Secondary outcomes (4)

Phase lb: Frequency and severity of adverse events
Incidence of adverse events (based on CTCAE Version 4) summarized by system organ class and/or preferred term, severity and relation to study treatment.
Measured: At screening, every week (C1D1, C1D8, C1D15, C1D22, C2D1, C2D8, etc.) until 30-45 days after treatment discontinuation [estimated time frame: 18 months].
Phase lb: Progression free survival (PFS)
PFS is defined as the time from start of treatment to objective tumor progression or death from any cause. Radiological assessments will be performed every 8 weeks.
Measured: At first treatment intake, every 8 weeks (C3D1, C5D1, C7D1, etc.) until disease progression or death for any cause [estimated time frame: 18 months].
Phase lb: Overall Response Rate (ORR)
Proportion of patients with a best overall response of CR or PR according to RECIST 1.1
Measured: At first treatment intake, every 8 weeks (C3D1, C5D1, C7D1, etc.) during the study [estimated time frame: 18 months].
Phase lb: Clinical Benefit Rate (CBR)
Proportion of patients with a best overall response of CR, PR or SD with a duration of 24 weeks or longer according to RECIST 1.1
Measured: At first treatment intake, every 8 weeks (C3D1, C5D1, C7D1, etc.) during the study [estimated time frame: 18 months].

Timeline

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

30 Jan 201219 May 2014

First posted19 Dec 2011 (estimated)
Study start30 Jan 2012
Primary completion19 May 2014
Study completion19 May 2014

Why it stopped: Study did not meet Phase Ib primary objective to establish the maximum tolerated dose/recommended dose for Phase II

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Inoperable Locally Advanced Breast CancerStudies of the same condition, open and under way.
More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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: Sequential
Masking: None (open label)
Enrolment: 18 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01495247
Sponsor's protocol ID: CBEZ235B2101
Other IDs: 2011-002400-32
Status last verified: Sep 2020
First submitted: 30 Sep 2011
Last updated: 8 Dec 2020
Results posted: No

Study at a glance

From the registry record, last updated by the sponsor on 8 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Dose-finding Phase Ib Study Followed by an Open-label, Randomized Phase II Study of BEZ235 Plus Paclitaxel in Patients With HER2 Negative, Inoperable Locally Advanced or Metastatic Breast Cancer
ClinicalTrials.gov ID: NCT01495247
Acronym / sponsor ID: CBEZ235B2101
Conditions: Inoperable Locally Advanced Breast Cancer, Metastatic Breast Cancer (MBC)
Keywords: Locally advanced, metastatic, breast cancer, HER2 negative, PI3K pathway, paclitaxel, mTOR inhibitor
Phase: Phase 1/2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Study did not meet Phase Ib primary objective to establish the maximum tolerated dose/recommended dose for Phase II
Enrolment: 18 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: 30 Jan 2012 (actual)
Primary completion: 19 May 2014 (actual)
Study completion: 19 May 2014 (actual)
First posted: 19 Dec 2011 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
BEZ235 100 mg bid + paclitaxel 80 mg (phase lb)	Experimental	Drug: BEZ235, Drug: PaclitaxelIncreasing doses of oral BEZ235 100 mg administered on a continuous twice daily (BID) schedule + weekly paclitaxel infusion at a fixed dose of 80 mg/m2. Treatment was organized into cycles of 28 days.
BEZ235 200 mg bid + paclitaxel 80 mg (phase lb)	Experimental	Drug: BEZ235, Drug: PaclitaxelIncreasing doses of oral BEZ235 200 mg administered on a continuous twice daily (BID) schedule + weekly paclitaxel infusion at a fixed dose of 80 mg/m2. Treatment was organized into cycles of 28 days

Who may qualify

Ages: 18 years and older
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Females with Breast cancer that is histologically or cytologically confirmed, HER2 negative and locally advanced or metastatic as confirmed by radiology
ECOG performance status 0 and 1
Adequate bone marrow and organ function

Key exclusion criteria (12 listed)

Previous treatment with PI3K and/or mTOR inhibitors
Symptomatic Central Nervous System (CNS) metastases
Concurrent malignancy or malignancy in the last 5 years prior to start of study treatment
Wide field radiotherapy ≤ 28 days or limited field radiation for palliation ≤ 14 days prior to starting study drug
Active cardiac disease (e.g. LVEF less than institutional lower limit of normal, QTcF > 480 msec, unstable angina pectoris, ventricular, supraventricular or nodal arrhythmias)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BEZ235Doses of oral BEZ235 (BID), supplied as 50mg, 200mg, 300mg or 400mg in SDS sachets, together with standard weekly paclitaxel at a fixed dose (80mg/m²) during 1h by i.v. in infusion.	Drug	BEZ235 100 mg bid + paclitaxel 80 mg (phase lb), BEZ235 200 mg bid + paclitaxel 80 mg (phase lb)
PaclitaxelThe paclitaxel infusion will be given in the morning and directly thereafter the BEZ235 dose will be given. BEZ235 doses will be escalated in cohorts of 3 to 6 patients guided by an adaptive Bayesian logistic regression model with overdose control until MTD/RP2D has been established. The initial dose level for the first cohort will be 200mg (BID), and then based on the Bayesian model the dose may be escalated to 300mg, 400mg, 500mg or 600mg for the next cohorts.	Drug	BEZ235 100 mg bid + paclitaxel 80 mg (phase lb), BEZ235 200 mg bid + paclitaxel 80 mg (phase lb)

Primary outcome

Phase lb: Dose Limiting Toxicities (DLTs) the first cycle of treatment
Time frame: At first treatment intake (Cycle 1 Day 1 = C1D1), C1D8, C1D15, C1D22 and C2D1 [a cycle = 4 weeks = 28 days]
DLT is defined as treatment-related toxicity (classified according Common Toxicity Criteria for Adverse Events (CTCAE) Version 4) occurring during the first 28 treatment days and meeting specific protocol-predefined criteria. The information will be integrated in a Bayesian logistic regression model with overdose control to estimate the maximum tolerated dose (MTD).

4 secondary outcomes

Phase lb: Frequency and severity of adverse events
Time frame: At screening, every week (C1D1, C1D8, C1D15, C1D22, C2D1, C2D8, etc.) until 30-45 days after treatment discontinuation [estimated time frame: 18 months].
Phase lb: Progression free survival (PFS)
Time frame: At first treatment intake, every 8 weeks (C3D1, C5D1, C7D1, etc.) until disease progression or death for any cause [estimated time frame: 18 months].
Phase lb: Overall Response Rate (ORR)
Time frame: At first treatment intake, every 8 weeks (C3D1, C5D1, C7D1, etc.) during the study [estimated time frame: 18 months].
Phase lb: Clinical Benefit Rate (CBR)
Time frame: At first treatment intake, every 8 weeks (C3D1, C5D1, C7D1, etc.) during the study [estimated time frame: 18 months].

Results and safety

The study was stopped early (reason given: Study did not meet Phase Ib primary objective to establish the maximum tolerated dose/recommended dose for Phase II). Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Dec 2020.
Results for CBEZ235B2101 can be found on the Novartis Clinical Trial Results WebsiteLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Novartis Pharmaceuticals study director

Novartis Pharmaceuticals

3 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing BEZ235 and Paclitaxel in people with Inoperable Locally Advanced Breast Cancer and Metastatic Breast Cancer (MBC), run by Novartis Pharmaceuticals at 3 sites in 2 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 3 inclusion and 12 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 8 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in France, 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 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?

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?

Phase lb: Dose Limiting Toxicities (DLTs) the first cycle of treatment (time frame: At first treatment intake (Cycle 1 Day 1 = C1D1), C1D8, C1D15, C1D22 and C2D1 [a cycle = 4 weeks = 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 NCT01495247.

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 2020.