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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01816594




Registration number
NCT01816594
Ethics application status
Date submitted
14/03/2013
Date registered
22/03/2013
Date last updated
14/11/2019

Titles & IDs
Public title
NeoPHOEBE: Neoadjuvant Trastuzumab + BKM120 in Combination With Weekly Paclitaxel in HER2-positive Primary Breast Cancer
Scientific 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
Secondary ID [1] 0 0
CBKM120F2203
Universal Trial Number (UTN)
Trial acronym
NeoPHOEBE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HER2-positive Newly Diagnosed, Primary Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - BKM120
Treatment: Drugs - Trastuzumab
Treatment: Drugs - Paclitaxel
Treatment: Drugs - BKM120 Placebo

Experimental: BKM120 + Trastuzumab + paclitaxel - BKM120 (oral, pan-class I PI3K inhibitor) in combination with trastuzumab and paclitaxel.

Placebo Comparator: BKM120 PBO + Trastuzumab + paclitaxel - BKM120 placebo in combination with trastuzumab and paclitaxel


Treatment: Drugs: BKM120
Neo-adjuvant BKM120 (oral pan-class I PI3K inhibitor, continuous daily dosing). BKM120 was administered orally 100 mg/day.

Treatment: Drugs: Trastuzumab
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.

Treatment: Drugs: Paclitaxel
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.

Treatment: Drugs: BKM120 Placebo
Neoadjuvant BKM120 placebo Administered orally 100 mg/day.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Pathological Complete Response (pCR) Rate at the Time of Surgery - All Participants
Timepoint [1] 0 0
After 6 weeks
Primary outcome [2] 0 0
Pathological Complete Response (pCR) Rate at the Time of Surgery - PIK3CA Wild Type (WT)
Timepoint [2] 0 0
After 6 weeks
Primary outcome [3] 0 0
Pathological Complete Response (pCR) Rate at the Time of Surgery - PIK3CA Mutant (MT)
Timepoint [3] 0 0
After 6 weeks
Secondary outcome [1] 0 0
Overall Objective Clinical Response Rate at the End of the Biologic Window (After Week 6) Compared to Baseline (Key Secondary) - All Participants
Timepoint [1] 0 0
After week 6
Secondary outcome [2] 0 0
Overall Objective Clinical Response Rate at the End of the Biologic Window (After Week 6) Compared to Baseline (Key Secondary) - PIK3A Wild Type Participants
Timepoint [2] 0 0
After week 6
Secondary outcome [3] 0 0
Overall Objective Clinical Response Rate at the End of the Biologic Window (After Week 6) Compared to Baseline (Key Secondary) - PIK3A Mutant Participants
Timepoint [3] 0 0
After week 6
Secondary outcome [4] 0 0
Rate of Breast Conserving Surgery (Most Radical Surgery)
Timepoint [4] 0 0
18 weeks
Secondary outcome [5] 0 0
Percentage of Participants With No Invasive and Non-invasive (DCIS) Residuals in Breast and Lymph Nodes Per GBG Definition
Timepoint [5] 0 0
After Week 6
Secondary outcome [6] 0 0
Percentage of Participants With No Invasive and Non-invasive (DCIS) Residuals in Breast and Lymph Nodes Per MD Anderson Definition
Timepoint [6] 0 0
After Week 6
Secondary outcome [7] 0 0
Overall Objective Response Rate (ORR) Prior to Surgery for All Participants
Timepoint [7] 0 0
prior to surgery
Secondary outcome [8] 0 0
Percentage of Participants With pCR Rates by Hormone Receptor Status - Positive Estrogen Receptor (ER+)
Timepoint [8] 0 0
After Week 6
Secondary outcome [9] 0 0
Percentage of Participants With pCR Rates by Hormone Receptor Status Negative Estrogen Receptor (ER-)
Timepoint [9] 0 0
After Week 6
Secondary outcome [10] 0 0
Percentage of Participants With Objective Response Rates by Hormone Receptor Status - Positive Estrogen Receptor (ER+)
Timepoint [10] 0 0
After Week 6
Secondary outcome [11] 0 0
Percentage of Participants With Objective Response Rates by Hormone Receptor Status - Negative Estrogen Receptor (ER-)
Timepoint [11] 0 0
After Week 6
Secondary outcome [12] 0 0
Percentage of Participants With Remaining Ductal Carcinoma in Situ (DCIS) (ypTis)
Timepoint [12] 0 0
18 weeks
Secondary outcome [13] 0 0
Percentage of Participants With Node-negative Disease at Definitive Surgery (ypN0)
Timepoint [13] 0 0
18 weeks

Eligibility
Key inclusion criteria
- 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
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
- 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

- 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
3/09/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
18/02/2015
Sample size
Target
Accrual to date
Final
50
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Parkville
Recruitment postcode(s) [1] 0 0
3002 - Parkville
Recruitment postcode(s) [2] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
Austria
State/province [1] 0 0
Salzburg
Country [2] 0 0
Germany
State/province [2] 0 0
Lubeck
Country [3] 0 0
Germany
State/province [3] 0 0
Offenbach
Country [4] 0 0
Spain
State/province [4] 0 0
Andalucia
Country [5] 0 0
Spain
State/province [5] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Breast International Group
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
German Breast Group
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
SOLTI Breast Cancer Research Group
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
Brief 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).
Trial website
https://clinicaltrials.gov/ct2/show/NCT01816594
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries