Patient case: 62-year-old male with cholangiocarcinoma; genetic feature: PIK3CA (1047H)

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

Summary: This randomized, parallel cohort, two stage, double-blind, placebo-controlled study will evaluate the oral PI3K inhibitor BKM120 in combination with trastuzumab and paclitaxel in HER2-positive primary breast cancer prior to definitive surgery (neo-adjuvant setting).

Detailed description: 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 >1.5 cm (by US or MRI) 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.

Eligibility: 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/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
  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
  -  Other protocol defined criteria may apply

Relevance to patient case: not relevant