NeoPHOEBE: Neoadjuvant Trastuzumab + BKM120 in Combination With Weekly Paclitaxel in HER2-positive Primary Breast Cancer
Condition: HER2-positive Newly Diagnosed, Primary Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: BKM120; Trastuzumab; Paclitaxel; BKM120 Placebo
Intervention description: Neo-adjuvant BKM120 (oral pan-class I PI3K inhibitor, continuous daily dosing). BKM120 was administered orally 100 mg/day.; 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.; 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.; Neoadjuvant BKM120 placebo Administered orally 100 mg/day.
Intervention MeSH terms: Paclitaxel; Trastuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 50.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HER2; breast cancer; neoadjuvant; PI3K inhibitor; first line chemotherapy; trastuzumab; GBG; SOLTI; BIG

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).
    

Eligibility criteria:

        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

        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