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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT01816594
Registration number
NCT01816594
Ethics application status
Date submitted
14/03/2013
Date registered
22/03/2013
Titles & IDs
Public title
NeoPHOEBE: Neoadjuvant Trastuzumab + BKM120 in Combination With Weekly Paclitaxel in HER2-positive Primary Breast Cancer
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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
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Secondary ID [1]
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CBKM120F2203
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Universal Trial Number (UTN)
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Trial acronym
NeoPHOEBE
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
HER2-positive Newly Diagnosed, Primary Breast Cancer
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Condition category
Condition code
Cancer
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Breast
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Intervention/exposure
Study type
Interventional
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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.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Pathological Complete Response (pCR) Rate at the Time of Surgery - All Participants
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Assessment method [1]
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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.
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Timepoint [1]
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After 6 weeks
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Primary outcome [2]
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Pathological Complete Response (pCR) Rate at the Time of Surgery - PIK3CA Wild Type (WT)
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Assessment method [2]
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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.
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Timepoint [2]
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After 6 weeks
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Primary outcome [3]
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Pathological Complete Response (pCR) Rate at the Time of Surgery - PIK3CA Mutant (MT)
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Assessment method [3]
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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.
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Timepoint [3]
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After 6 weeks
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Secondary outcome [1]
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Overall Objective Clinical Response Rate at the End of the Biologic Window (After Week 6) Compared to Baseline (Key Secondary) - All Participants
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Assessment method [1]
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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.
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Timepoint [1]
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After week 6
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Secondary outcome [2]
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Overall Objective Clinical Response Rate at the End of the Biologic Window (After Week 6) Compared to Baseline (Key Secondary) - PIK3A Wild Type Participants
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Assessment method [2]
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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.
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Timepoint [2]
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After week 6
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Secondary outcome [3]
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Overall Objective Clinical Response Rate at the End of the Biologic Window (After Week 6) Compared to Baseline (Key Secondary) - PIK3A Mutant Participants
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Assessment method [3]
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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.
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Timepoint [3]
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After week 6
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Secondary outcome [4]
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Rate of Breast Conserving Surgery (Most Radical Surgery)
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Assessment method [4]
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Rate of patients with breast conserving surgery. Participants who did not have breast surgery were also considered as having breast conservation surgery (BCS)
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Timepoint [4]
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18 weeks
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Secondary outcome [5]
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Percentage of Participants With No Invasive and Non-invasive (DCIS) Residuals in Breast and Lymph Nodes Per GBG Definition
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Assessment method [5]
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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.
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Timepoint [5]
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After Week 6
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Secondary outcome [6]
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Percentage of Participants With No Invasive and Non-invasive (DCIS) Residuals in Breast and Lymph Nodes Per MD Anderson Definition
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Assessment method [6]
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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.
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Timepoint [6]
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After Week 6
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Secondary outcome [7]
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Overall Objective Response Rate (ORR) Prior to Surgery for All Participants
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Assessment method [7]
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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.
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Timepoint [7]
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prior to surgery
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Secondary outcome [8]
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Percentage of Participants With pCR Rates by Hormone Receptor Status - Positive Estrogen Receptor (ER+)
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Assessment method [8]
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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.
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Timepoint [8]
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After Week 6
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Secondary outcome [9]
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Percentage of Participants With pCR Rates by Hormone Receptor Status Negative Estrogen Receptor (ER-)
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Assessment method [9]
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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.
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Timepoint [9]
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After Week 6
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Secondary outcome [10]
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Percentage of Participants With Objective Response Rates by Hormone Receptor Status - Positive Estrogen Receptor (ER+)
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Assessment method [10]
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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.
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Timepoint [10]
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After Week 6
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Secondary outcome [11]
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Percentage of Participants With Objective Response Rates by Hormone Receptor Status - Negative Estrogen Receptor (ER-)
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Assessment method [11]
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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.
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Timepoint [11]
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After Week 6
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Secondary outcome [12]
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Percentage of Participants With Remaining Ductal Carcinoma in Situ (DCIS) (ypTis)
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Assessment method [12]
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This included participants at definitive surgery irrespective of lymph node status
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Timepoint [12]
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18 weeks
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Secondary outcome [13]
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Percentage of Participants With Node-negative Disease at Definitive Surgery (ypN0)
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Assessment method [13]
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Node-negative disease at definitive surgery (ypN0) were considered as binary variables of 'response' versus 'non response'.
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Timepoint [13]
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18 weeks
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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
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Females
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Can healthy volunteers participate?
No
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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
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
3/09/2013
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
18/02/2015
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Sample size
Target
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Accrual to date
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Final
50
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Recruitment in Australia
Recruitment state(s)
VIC
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Recruitment hospital [1]
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Novartis Investigative Site - Parkville
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Recruitment postcode(s) [1]
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3002 - Parkville
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Recruitment postcode(s) [2]
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3050 - Parkville
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Recruitment outside Australia
Country [1]
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Austria
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State/province [1]
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Salzburg
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Country [2]
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Germany
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State/province [2]
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Lubeck
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Country [3]
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Germany
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State/province [3]
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Offenbach
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Country [4]
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Spain
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State/province [4]
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Andalucia
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Country [5]
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Spain
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State/province [5]
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Madrid
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Novartis Pharmaceuticals
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Address
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Other collaborator category [1]
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Other
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Name [1]
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Breast International Group
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Address [1]
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Country [1]
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Other collaborator category [2]
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Other
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Name [2]
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German Breast Group
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Address [2]
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Other collaborator category [3]
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Other
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Name [3]
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SOLTI Breast Cancer Research Group
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Address [3]
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Country [3]
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Ethics approval
Ethics application status
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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).
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Trial website
https://clinicaltrials.gov/study/NCT01816594
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Trial related presentations / 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.
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Public notes
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Contacts
Principal investigator
Name
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Novartis Pharmaceuticals
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Address
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Novartis Pharmaceuticals
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Country
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Phone
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Fax
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Email
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Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
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What data in particular will be shared?
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
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When will data be available (start and end dates)?
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Available to whom?
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Available for what types of analyses?
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How or where can data be obtained?
IPD available at link: http://www.clinicalstudydatarequest.com
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What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results are available at
https://clinicaltrials.gov/study/NCT01816594