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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


Phase 2
18 Years
N/A
Not Enrolling
Female
HER2-positive Newly Diagnosed Primary Breast Cancer

Thank you

Trial Information

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


NeoPHOEBE will evaluate 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 >2cm with centrally
confirmed HER2 overexpression or amplification, and who have not previously undergone
treatment for invasive breast cancer.

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

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

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

After completion of study treatment, patients will undergo definitive surgery.


Inclusion Criteria:



- Patient is 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
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

Exclusion Criteria:

- Patient has received previous treatment with PI3K inhibitors

- 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 55% 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 moderate or 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

- Other protocol defined criteria may apply

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Outcome Measure:

Pathological complete response (pCR) rate

Outcome Description:

Rate of pCR (as defined by NSABP criteria - absence of invasive disease in the breast [ypT0]) at the time of surgery.

Outcome Time Frame:

week 18

Safety Issue:

No

Principal Investigator

Novartis Pharmaceuticals

Investigator Role:

Study Director

Investigator Affiliation:

Novartis Pharmaceuticals

Authority:

Australia: Department of Health and Ageing Therapeutic Goods Administration

Study ID:

CBKM120F2203

NCT ID:

NCT01816594

Start Date:

March 2013

Completion Date:

July 2015

Related Keywords:

  • HER2-positive Newly Diagnosed Primary Breast Cancer
  • HER2
  • breast cancer
  • neoadjuvant
  • PI3K inhibitor
  • first line chemotherapy
  • trastuzumab
  • GBG
  • SOLTI
  • BIG
  • neoadjuvant therapy
  • Breast Neoplasms

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