HER2-positive Newly Diagnosed, Primary Breast CancerPhase 2NeoPHOEBENCT01816594

NeoPHOEBE: Neoadjuvant Trastuzumab + BKM120 in Combination With Weekly Paclitaxel in HER2-positive Primary Breast Cancer

A Phase 2 study testing BKM120, Trastuzumab and Paclitaxel in people with HER2-positive Newly Diagnosed, Primary Breast Cancer, run by Novartis Pharmaceuticals at 7 sites in 4 countries.

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 randomized, parallel cohort, two stage, double-blind, placebo-controlled study evaluated the oral PI3K inhibitor BKM120 in combination with trastuzumab and paclitaxel in HER2-positive, PIK3CA wild-type and PIK3CA mutant primary breast cancer prior to surgery (neo-adjuvant setting). Read more about this study

Who is it for?: Ages 18 years and older, women only
Conditions the study is for: HER2-positive Newly Diagnosed, Primary Breast Cancer
What is being tested?: BKM120, Trastuzumab and Paclitaxel
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 50 participants
Where: 7 sitesin 4 countries
Study dates: 3 Sep 2013to 18 Feb 2015
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

Patient had provided a signed study ICF prior to any screening procedure
Patient was a female ≥ 18 years of age
Patient has an ECOG performance status of 0-1
Patient has a unilateral (multifocal or multicentric disease allowed), histologically confirmed, newly diagnosed early breast cancer >2cm by clinical examination and/or >1.5 cm confirmed by ultrasound or by MRI
Patient has tumor tissue available for central review of ER, HER2 and PI3K status with centrally confirmed HER2-positive disease and known PI3KCA mutation status
Patient has adequate bone marrow, renal and liver function
Patient is able to swallow and retain oral medication

Who cannot join

Patient has received prior systemic treatment for currently diagnosed disease
Patient has a known contraindications, hypersensitivity or intolerance to trastuzumab, paclitaxel or products containing cremophor
Patient has bilateral breast cancer or metastatic disease or inflammatory breast cancer
LVEF below 50% as determined by MUGA scan or ECHO
Patient has active cardiac disease or a history of cardiac abnormalities as defined in the protocol
Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKM120

Show all 11Show fewer

Patient is currently receiving warfarin or other coumarin derived anti-coagulants
Patient is currently receiving chronic treatment with corticosteroids or another immunosuppressive agents (standard premedication for paclitaxel and local applications allowed)
Patient is currently receiving treatment with drugs known to be strong inhibitors or inducers of CYP3A
Patient has certain scores on an anxiety and depression mood questionnaires
Pregnant or nursing (lactating) women or patients not willing to apply apply highly effective contraception as defined in the protocol

Trial locations and contacts

7 sites in 4 countries.

Country

City, postcode or hospital

7 sites in 4 countries

Australia2 sites

Novartis Investigative Site
Parkville, Victoria, 3002
Novartis Investigative Site
Parkville, Victoria, 3050

Other trials in Australia

Germany2 sites

Novartis Investigative Site
Lübeck, 23538
Novartis Investigative Site
Offenbach, 63069

Other trials in Germany

Spain2 sites

Novartis Investigative Site
Madrid, 28222
Novartis Investigative Site
Seville, Andalusia, 41013

Other trials in Spain

Austria1 site

Novartis Investigative Site
Salzburg, 5020

Other trials in Austria

About this study

Official title: NeoPHOEBE: Pi3k Inhibition in Her2 OverExpressing Breast cancEr: A Phase II, Randomized, Parallel Cohort, Two Stage, Double-blind, Placebo-controlled Study of Neoadjuvant Trastuzumab Versus Trastuzumab + BKM120 in Combination With Weekly Paclitaxel in HER2-positive, PIK3CA Wild-type and PIK3CA Mutant Primary Breast Cancer

Read the detailed description

NeoPHOEBE evaluated the efficacy (as defined by pCR) of BKM120 (an oral PI3K inhibitor) in combination with trastuzumab and paclitaxel in a randomized, placebo-controlled, neo-adjuvant study in women diagnosed with primary breast cancer >1.5 cm (by US or MRI) with centrally confirmed HER2 overexpression or amplification, who have not previously undergone treatment for invasive breast cancer.

Prior to the initiation of paclitaxel, there was a 6-week "biologic window" with trastuzumab plus BKM120 or placebo only. The study was conducted separately in two cohorts (PIK3CA mutated and PI3K3CA wild-type) using a two-stage approach. Within each cohort patients were randomized into one of the following treatment arms:

Arm 1: BKM120 plus trastuzumab for 6 weeks followed by BKM120 and trastuzumab plus weekly paclitaxel for an additional 12 weeks.

Arm 2: BKM120 placebo plus trastuzumab for 6 weeks followed by BKM120 placebo plus trastuzumab plus weekly paclitaxel for an additional 12 weeks.

After completion of study treatment, patients were to have undergone definitive surgery.

Conditions: HER2-positive Newly Diagnosed, Primary Breast Cancer
Being tested: BKM120, Trastuzumab, Paclitaxel, BKM120 Placebo
Keywords: HER2, breast cancer, neoadjuvant, PI3K inhibitor, first line chemotherapy, trastuzumab, GBG, SOLTI, BIG
Medical subject headings: Breast Neoplasms

What participants receive

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

BKM120Drug
Also called Buparsilib
Neo-adjuvant BKM120 (oral pan-class I PI3K inhibitor, continuous daily dosing). BKM120 was administered orally 100 mg/day.
TrastuzumabDrug
Trastuzumab is a humanized monoclonal antibody directed against the extracellular juxtamembrane domain of the HER2 receptor. Administered 4mg/kg i.v. load followed by 2mg/kg i.v. weekly.
PaclitaxelDrug
Paclitaxel is a cytotoxic agent with proven antitumor activity in a variety of solid tumors. The antitumor activity of paclitaxel is based on tubulin-binding and stabilization of non-functional microtubule bundles, thereby blocking normal mitotic spindle development and subsequent cell division. Administered weekly 80mg/m2 i.v.
BKM120 PlaceboDrug
Neoadjuvant BKM120 placebo Administered orally 100 mg/day.

Study groups in NCT01816594
Study group	Role	What they receive
BKM120 + Trastuzumab + paclitaxel	Experimental	BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel. Receives: Drug: BKM120; Drug: Trastuzumab; Drug: Paclitaxel
BKM120 PBO + Trastuzumab + paclitaxel	Placebo comparator	BKM120 placebo in combination with trastuzumab and paclitaxel Receives: Drug: Trastuzumab; Drug: Paclitaxel; Drug: BKM120 Placebo

What is being measured

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

Pathological Complete Response (pCR) Rate at the Time of Surgery - All Participants
Rate of pCR (as defined by NSABP criteria - absence of invasive disease in the breast [ypT0]) is the number of of participants with pathological complete response (pCR) at the time of surgery. Participants were to be considered in pCR if there was no invasive cancer in the breast or only non-invasive in situ cancer in the breast specimen. NSABP guidelines do not take into account the histological nodal status to define the pCR.
Measured: After 6 weeks
Pathological Complete Response (pCR) Rate at the Time of Surgery - PIK3CA Wild Type (WT)
Rate of pCR (as defined by NSABP criteria - absence of invasive disease in the breast [ypT0]) is the number of of participants with pathological complete response (pCR) at the time of surgery. Participants were to be considered in pCR if there was no invasive cancer in the breast or only non-invasive in situ cancer in the breast specimen. NSABP guidelines do not take into account the histological nodal status to define the pCR.
Measured: After 6 weeks
Pathological Complete Response (pCR) Rate at the Time of Surgery - PIK3CA Mutant (MT)
Rate of pCR (as defined by NSABP criteria - absence of invasive disease in the breast [ypT0]) is the number of of participants with pathological complete response (pCR) at the time of surgery. Participants were to be considered in pCR if there was no invasive cancer in the breast or only non-invasive in situ cancer in the breast specimen. NSABP guidelines do not take into account the histological nodal status to define the pCR.
Measured: After 6 weeks

Secondary outcomes (13)

Overall Objective Clinical Response Rate at the End of the Biologic Window (After Week 6) Compared to Baseline (Key Secondary) - All Participants
Percentage of Overall objective clinical response rate = Complete Response + Partial Response rate, measured by US bidimentional ulltrasound (or MRI) and assessed by world health organization (WHO) criteria.
Measured: After week 6
Overall Objective Clinical Response Rate at the End of the Biologic Window (After Week 6) Compared to Baseline (Key Secondary) - PIK3A Wild Type Participants
Percentage of Overall objective clinical response rate = Complete Response + Partial Response rate, measured by US bidimentional ulltrasound (or MRI) and assessed by world health organization (WHO) criteria.
Measured: After week 6
Overall Objective Clinical Response Rate at the End of the Biologic Window (After Week 6) Compared to Baseline (Key Secondary) - PIK3A Mutant Participants
Percentage of Overall objective clinical response rate = Complete Response + Partial Response rate, measured by US bidimentional ulltrasound (or MRI) and assessed by world health organization (WHO) criteria.
Measured: After week 6
Rate of Breast Conserving Surgery (Most Radical Surgery)
Rate of patients with breast conserving surgery. Participants who did not have breast surgery were also considered as having breast conservation surgery (BCS)
Measured: 18 weeks
Percentage of Participants With No Invasive and Non-invasive (DCIS) Residuals in Breast and Lymph Nodes Per GBG Definition
Rate of pCR defined as no invasive and non-invasive (DCIS) residuals in breast and lymph nodes (ypT0, ypN0 [GBG definition]). If patient had a sentinel node biopsy before treatment which was negative and no axilla dissection was performed after treatment completion, such patient was considered to be pN0 for both secondary pCR definitions. Surgical breast and axillary node resection specimens were evaluated for pathologic tumor response according to NSABP guidelines.
Measured: After Week 6
Percentage of Participants With No Invasive and Non-invasive (DCIS) Residuals in Breast and Lymph Nodes Per MD Anderson Definition
Rate of pCR defined as no invasive residuals in breast and lymph nodes (ypT0/Tis, ypN0 [MD Anderson definition]). If a patient had a sentinel node biopsy before treatment which was negative and no axilla dissection was performed after treatment completion, such patient was considered to be pN0 for both secondary pCR definitions.
Measured: After Week 6
Overall Objective Response Rate (ORR) Prior to Surgery for All Participants
Number of Overall objective response rate = Complete Response + Partial Response rate, measured by US bidimentional ulltrasound (or MRI) and assessed by world health organization (WHO) criteria. CR: Complete disappearance of all tumor signs in the breast as assessed by ultrasound or MRI. The response of the axillary nodes was not to be considered. PR: Reduction in the product of the two largest perpendicular diameters of the primary tumor size by 50% or more assessed by ultrasound or MRI. In patients with multifocal or multicentric disease, the lesion with the largest diameters should be chosen for follow-up. The response of the axillary nodes was not to be considered.
Measured: prior to surgery
Percentage of Participants With pCR Rates by Hormone Receptor Status - Positive Estrogen Receptor (ER+)
pCR defined as no invasive and non-invasive (DCIS) residuals in breast and lymph nodes (ypT0, ypN0 [GBG definition]); pCR defined as no invasive residuals in breast and lymph nodes (ypT0/Tis, ypN0 [MD Anderson definition]). If participant had a sentinel node biopsy before treatment which was negative and no axilla dissection was performed after treatment completion, such participant was considered to be pN0 for both secondary pCR definitions.
Measured: After Week 6
Percentage of Participants With pCR Rates by Hormone Receptor Status Negative Estrogen Receptor (ER-)
pCR defined as no invasive and non-invasive (DCIS) residuals in breast and lymph nodes (ypT0, ypN0 [GBG definition]); pCR defined as no invasive residuals in breast and lymph nodes (ypT0/Tis, ypN0 [MD Anderson definition]). If participant had a sentinel node biopsy before treatment which was negative and no axilla dissection was performed after treatment completion, such participant was considered to be pN0 for both secondary pCR definitions.
Measured: After Week 6
Percentage of Participants With Objective Response Rates by Hormone Receptor Status - Positive Estrogen Receptor (ER+)
Objective response rate = Complete Response + Partial Response rate, measured by US bidimentional ulltrasound (or MRI) and assessed by world health organization (WHO) criteria. CR: Complete disappearance of all tumor signs in the breast as assessed by ultrasound or MRI. The response of the axillary nodes was not to be considered. PR: Reduction in the product of the two largest perpendicular diameters of the primary tumor size by 50% or more assessed by ultrasound or MRI. In patients with multifocal or multicentric disease, the lesion with the largest diameters should be chosen for follow-up. The response of the axillary nodes was not to be considered.
Measured: After Week 6
Percentage of Participants With Objective Response Rates by Hormone Receptor Status - Negative Estrogen Receptor (ER-)
Objective response rate = Complete Response + Partial Response rate, measured by US bidimentional ulltrasound (or MRI) and assessed by world health organization (WHO) criteria. CR: Complete disappearance of all tumor signs in the breast as assessed by ultrasound or MRI. The response of the axillary nodes was not to be considered. PR: Reduction in the product of the two largest perpendicular diameters of the primary tumor size by 50% or more assessed by ultrasound or MRI. In patients with multifocal or multicentric disease, the lesion with the largest diameters should be chosen for follow-up. The response of the axillary nodes was not to be considered.
Measured: After Week 6
Percentage of Participants With Remaining Ductal Carcinoma in Situ (DCIS) (ypTis)
This included participants at definitive surgery irrespective of lymph node status
Measured: 18 weeks
Percentage of Participants With Node-negative Disease at Definitive Surgery (ypN0)
Node-negative disease at definitive surgery (ypN0) were considered as binary variables of 'response' versus 'non response'.
Measured: 18 weeks

Timeline

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

3 Sep 201318 Feb 2015

First posted22 Mar 2013 (estimated)
Study start3 Sep 2013
Primary completion18 Feb 2015
Study completion18 Feb 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for HER2-positive Newly Diagnosed, Primary 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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 50 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01816594
Sponsor's protocol ID: CBKM120F2203
Acronym: NeoPHOEBE
Status last verified: Oct 2019
First submitted: 14 Mar 2013
Last updated: 14 Nov 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Publications

Loibl S, de la Pena L, Nekljudova V, Zardavas D, Michiels S, Denkert C, Rezai M, Bermejo B, Untch M, Lee SC, Turri S, Urban P, Kummel S, Steger G, Gombos A, Lux M, Piccart MJ, Von Minckwitz G, Baselga J, Loi S. Neoadjuvant buparlisib plus trastuzumab and paclitaxel for women with HER2+ primary breast cancer: A randomised, double-blind, placebo-controlled phase II trial (NeoPHOEBE). Eur J Cancer. 2017 Nov;85:133-145. doi: 10.1016/j.ejca.2017.08.020. Epub 2017 Sep 17.
PubMed 28923573

Study at a glance

From the registry record, last updated by the sponsor on 14 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: NeoPHOEBE: Pi3k Inhibition in Her2 OverExpressing Breast cancEr: A Phase II, Randomized, Parallel Cohort, Two Stage, Double-blind, Placebo-controlled Study of Neoadjuvant Trastuzumab Versus Trastuzumab + BKM120 in Combination With Weekly Paclitaxel in HER2-positive, PIK3CA Wild-type and PIK3CA Mutant Primary Breast Cancer
ClinicalTrials.gov ID: NCT01816594
Acronym / sponsor ID: NeoPHOEBE / CBKM120F2203
Conditions: HER2-positive Newly Diagnosed, Primary Breast Cancer
Keywords: HER2, breast cancer, neoadjuvant, PI3K inhibitor, first line chemotherapy, trastuzumab, GBG, SOLTI
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 50 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Collaborators: Breast International Group, GBG Forschungs GmbH, SOLTI Breast Cancer Research Group
Study start: 3 Sep 2013 (actual)
Primary completion: 18 Feb 2015 (actual)
Study completion: 18 Feb 2015 (actual)
First posted: 22 Mar 2013 (estimated)
Results: Posted 14 Nov 2019

Clinical summary

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

Detailed description

Arm 1: BKM120 plus trastuzumab for 6 weeks followed by BKM120 and trastuzumab plus weekly paclitaxel for an additional 12 weeks.

Arm 2: BKM120 placebo plus trastuzumab for 6 weeks followed by BKM120 placebo plus trastuzumab plus weekly paclitaxel for an additional 12 weeks.

After completion of study treatment, patients were to have undergone definitive surgery.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2

Arm	Type	Receives
BKM120 + Trastuzumab + paclitaxel	Experimental	Drug: BKM120, Drug: Trastuzumab, Drug: PaclitaxelBKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel.
BKM120 PBO + Trastuzumab + paclitaxel	Placebo comparator	Drug: Trastuzumab, Drug: Paclitaxel, Drug: BKM120 PlaceboBKM120 placebo in combination with trastuzumab and paclitaxel

Who may qualify

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

Key inclusion criteria (7 listed)

Patient had provided a signed study ICF prior to any screening procedure
Patient was a female ≥ 18 years of age
Patient has an ECOG performance status of 0-1
Patient has a unilateral (multifocal or multicentric disease allowed), histologically confirmed, newly diagnosed early breast cancer >2cm by clinical examination and/or >1.5 cm confirmed by ultrasound or by MRI
Patient has tumor tissue available for central review of ER, HER2 and PI3K status with centrally confirmed HER2-positive disease and known PI3KCA mutation status

Key exclusion criteria (11 listed)

Patient has received prior systemic treatment for currently diagnosed disease
Patient has a known contraindications, hypersensitivity or intolerance to trastuzumab, paclitaxel or products containing cremophor
Patient has bilateral breast cancer or metastatic disease or inflammatory breast cancer
LVEF below 50% as determined by MUGA scan or ECHO
Patient has active cardiac disease or a history of cardiac abnormalities as defined in the protocol

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
BKM120Also: BuparsilibNeo-adjuvant BKM120 (oral pan-class I PI3K inhibitor, continuous daily dosing). BKM120 was administered orally 100 mg/day.	Drug	BKM120 + Trastuzumab + paclitaxel
TrastuzumabTrastuzumab is a humanized monoclonal antibody directed against the extracellular juxtamembrane domain of the HER2 receptor. Administered 4mg/kg i.v. load followed by 2mg/kg i.v. weekly.	Drug	BKM120 + Trastuzumab + paclitaxel, BKM120 PBO + Trastuzumab + paclitaxel
PaclitaxelPaclitaxel is a cytotoxic agent with proven antitumor activity in a variety of solid tumors. The antitumor activity of paclitaxel is based on tubulin-binding and stabilization of non-functional microtubule bundles, thereby blocking normal mitotic spindle development and subsequent cell division. Administered weekly 80mg/m2 i.v.	Drug	BKM120 + Trastuzumab + paclitaxel, BKM120 PBO + Trastuzumab + paclitaxel
BKM120 PlaceboNeoadjuvant BKM120 placebo Administered orally 100 mg/day.	Drug	BKM120 PBO + Trastuzumab + paclitaxel

Primary outcome

Pathological Complete Response (pCR) Rate at the Time of Surgery - All Participants
Time frame: After 6 weeks
Rate of pCR (as defined by NSABP criteria - absence of invasive disease in the breast [ypT0]) is the number of of participants with pathological complete response (pCR) at the time of surgery. Participants were to be considered in pCR if there was no invasive cancer in the breast or only non-invasive in situ cancer in the breast specimen. NSABP guidelines do not take into account the histological nodal status to define the pCR.
Pathological Complete Response (pCR) Rate at the Time of Surgery - PIK3CA Wild Type (WT)
Time frame: After 6 weeks
Rate of pCR (as defined by NSABP criteria - absence of invasive disease in the breast [ypT0]) is the number of of participants with pathological complete response (pCR) at the time of surgery. Participants were to be considered in pCR if there was no invasive cancer in the breast or only non-invasive in situ cancer in the breast specimen. NSABP guidelines do not take into account the histological nodal status to define the pCR.
Pathological Complete Response (pCR) Rate at the Time of Surgery - PIK3CA Mutant (MT)
Time frame: After 6 weeks
Rate of pCR (as defined by NSABP criteria - absence of invasive disease in the breast [ypT0]) is the number of of participants with pathological complete response (pCR) at the time of surgery. Participants were to be considered in pCR if there was no invasive cancer in the breast or only non-invasive in situ cancer in the breast specimen. NSABP guidelines do not take into account the histological nodal status to define the pCR.

13 secondary outcomes

Overall Objective Clinical Response Rate at the End of the Biologic Window (After Week 6) Compared to Baseline (Key Secondary) - All Participants
Time frame: After week 6
Overall Objective Clinical Response Rate at the End of the Biologic Window (After Week 6) Compared to Baseline (Key Secondary) - PIK3A Wild Type Participants
Time frame: After week 6
Overall Objective Clinical Response Rate at the End of the Biologic Window (After Week 6) Compared to Baseline (Key Secondary) - PIK3A Mutant Participants
Time frame: After week 6
Rate of Breast Conserving Surgery (Most Radical Surgery)
Time frame: 18 weeks
Percentage of Participants With No Invasive and Non-invasive (DCIS) Residuals in Breast and Lymph Nodes Per GBG Definition
Time frame: After Week 6
Percentage of Participants With No Invasive and Non-invasive (DCIS) Residuals in Breast and Lymph Nodes Per MD Anderson Definition
Time frame: After Week 6
Overall Objective Response Rate (ORR) Prior to Surgery for All Participants
Time frame: prior to surgery
Percentage of Participants With pCR Rates by Hormone Receptor Status - Positive Estrogen Receptor (ER+)
Time frame: After Week 6
Percentage of Participants With pCR Rates by Hormone Receptor Status Negative Estrogen Receptor (ER-)
Time frame: After Week 6
Percentage of Participants With Objective Response Rates by Hormone Receptor Status - Positive Estrogen Receptor (ER+)
Time frame: After Week 6
Percentage of Participants With Objective Response Rates by Hormone Receptor Status - Negative Estrogen Receptor (ER-)
Time frame: After Week 6
Percentage of Participants With Remaining Ductal Carcinoma in Situ (DCIS) (ypTis)
Time frame: 18 weeks
Percentage of Participants With Node-negative Disease at Definitive Surgery (ypN0)
Time frame: 18 weeks

Results and safety

Results posted to the registry on 14 Nov 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Trastuzumab + BKM120 + Paclitaxel	25	14
Trastuzumab + BKM120 PBO + Paclitaxel	25	23

Primary outcome: Pathological Complete Response (pCR) Rate at the Time of Surgery - All Participants

Time frame: After 6 weeks. Number (95% Confidence Interval). Unit: Percentage of participants

Measure	Trastuzumab + BKM120 + Paclitaxel n = 25	Trastuzumab + BKM120 PBO + Paclitaxel n = 25
Value	32.0 (14.9 to 53.5)	40.0 (21.1 to 61.3)

Trastuzumab + BKM120 + Paclitaxel vs Trastuzumab + BKM120 PBO + Paclitaxel: p = 0.811, Fisher Exact

Population analysed: Intent-to-treat set (ITT)/full analysis set (FAS) (pooled): The full analysis set comprised all patients to whom study treatment had been assigned by randomization. Patients who were randomized but did not start study treatment were not replaced and were considered as treatment failures similarly to other patients with no pCR assessment.

Primary outcome: Pathological Complete Response (pCR) Rate at the Time of Surgery - PIK3CA Wild Type (WT)

Time frame: After 6 weeks. Number (95% Confidence Interval). Unit: Percentage of participants

Measure	Trastuzumab + BKM120 + Paclitaxel n = 21	Trastuzumab + BKM120 PBO + Paclitaxel n = 21
Value	33.3 (14.6 to 57.0)	42.9 (21.8 to 66.0)

Trastuzumab + BKM120 + Paclitaxel vs Trastuzumab + BKM120 PBO + Paclitaxel: p = 0.830, Fisher Exact

Primary outcome: Pathological Complete Response (pCR) Rate at the Time of Surgery - PIK3CA Mutant (MT)

Time frame: After 6 weeks. Number (95% Confidence Interval). Unit: Percentage of participants

Measure	Trastuzumab + BKM120 + Paclitaxel n = 4	Trastuzumab + BKM120 PBO + Paclitaxel n = 4
Value	25.0 (0.6 to 80.6)	25.0 (0.6 to 80.6)

Trastuzumab + BKM120 + Paclitaxel vs Trastuzumab + BKM120 PBO + Paclitaxel: p = 0.786, Fisher Exact

13 secondary outcomes are reported in the full results.

Adverse events

Time frame: AEs and SAEs were collected for the maximum duration of treatment and follow up for a participant per protocol for a median of approximately 18 months. All cause mortality (deaths) was collected from First Patient First Visit (FPFV) to Last Patient Last Visit (LPLV) up to a maximum of approx. 18 months.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Trastuzumab + BKM120 + Paclitaxel	8 of 25 (32%)	21 of 25 (84%)	0 of 25
Trastuzumab + BKM120 PBO + Paclitaxel	2 of 25 (8%)	19 of 25 (76%)	0 of 25

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 28923573Loibl S, de la Pena L, Nekljudova V, Zardavas D, Michiels S, Denkert C, Rezai M, Bermejo B, Untch M, Lee SC, Turri S, Urban P, Kummel S, Steger G, Gombos A, Lux M, Piccart MJ, Von Minckwitz G, Baselga J, Loi S. Neoadjuvant buparlisib plus trastuzumab and paclitaxel for women with HER2+ primary breast cancer: A randomised, double-blind, placebo-controlled phase II trial (NeoPHOEBE). Eur J Cancer. 2017 Nov;85:133-145. doi: 10.1016/j.ejca.2017.08.020. Epub 2017 Sep 17.
Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

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

7 sites in 4 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing BKM120, Trastuzumab and Paclitaxel in people with HER2-positive Newly Diagnosed, Primary Breast Cancer, run by Novartis Pharmaceuticals at 7 sites in 4 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 7 inclusion and 11 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 14 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Australia, Germany, Spain, Austria. 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. Some participants in this study may receive a placebo. 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 14 Nov 2019). 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?

Pathological Complete Response (pCR) Rate at the Time of Surgery - All Participants (time frame: After 6 weeks). The study lists 3 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 NCT01816594, which also lists 1 linked publication.

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 14 Nov 2019.