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

NCT01816594 | Completed Phase 2 Results DMC

• 1 other identifier: CBKM120F2203
• Study Type: interventional
• Target: 50
• Locations: 3 countries
• Sites: 5

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).

Conditions

HER2-positive Newly Diagnosed, Primary Breast Cancer

Keywords

HER2; breast cancer; neoadjuvant; PI3K inhibitor; first line chemotherapy; trastuzumab; GBG; SOLTI; BIG

Outcome Measures

Primary Outcomes (3)

• Pathological Complete Response (pCR) Rate at the Time of Surgery - All Participants

  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.

  After 6 weeks

• Pathological Complete Response (pCR) Rate at the Time of Surgery - PIK3CA Wild Type (WT)

  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.

  After 6 weeks

• Pathological Complete Response (pCR) Rate at the Time of Surgery - PIK3CA Mutant (MT)

  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.

  After 6 weeks

Secondary Outcomes (13)

• Overall Objective Clinical Response Rate at the End of the Biologic Window (After Week 6) Compared to Baseline (Key Secondary) - All Participants

  After week 6

• Overall Objective Clinical Response Rate at the End of the Biologic Window (After Week 6) Compared to Baseline (Key Secondary) - PIK3A Wild Type Participants

  After week 6

• Overall Objective Clinical Response Rate at the End of the Biologic Window (After Week 6) Compared to Baseline (Key Secondary) - PIK3A Mutant Participants

  After week 6

• Rate of Breast Conserving Surgery (Most Radical Surgery)

  18 weeks

• Percentage of Participants With No Invasive and Non-invasive (DCIS) Residuals in Breast and Lymph Nodes Per GBG Definition

  After Week 6

Study Arms (2)

BKM120 + Trastuzumab + paclitaxel

EXPERIMENTAL

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

Drug: BKM120; Drug: Trastuzumab; Drug: Paclitaxel

BKM120 PBO + Trastuzumab + paclitaxel

PLACEBO COMPARATOR

BKM120 placebo in combination with trastuzumab and paclitaxel

Drug: Trastuzumab; Drug: Paclitaxel; Drug: BKM120 Placebo

Interventions

BKM120 DRUG

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

Also known as: Buparsilib

BKM120 + Trastuzumab + paclitaxel

Trastuzumab DRUG

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.

BKM120 + Trastuzumab + paclitaxel; BKM120 PBO + Trastuzumab + paclitaxel

Paclitaxel DRUG

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.

BKM120 + Trastuzumab + paclitaxel; BKM120 PBO + Trastuzumab + paclitaxel

BKM120 Placebo DRUG

Neoadjuvant BKM120 placebo Administered orally 100 mg/day.

BKM120 PBO + Trastuzumab + paclitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead
• Breast International Group: collaborator
• GBG Forschungs GmbH: collaborator
• SOLTI Breast Cancer Research Group: collaborator

Study Sites (7)

Novartis Investigative Site

Parkville, Victoria, 3002, Australia

Location

Novartis Investigative Site

Parkville, Victoria, 3050, Australia

Location

Novartis Investigative Site

Salzburg, 5020, Austria

Location

Novartis Investigative Site

Lübeck, 23538, Germany

Location

Novartis Investigative Site

Offenbach, 63069, Germany

Location

Novartis Investigative Site

Seville, Andalusia, 41013, Spain

Location

Novartis Investigative Site

Madrid, 28222, Spain

Location

Related Publications (1)

• 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.

  PMID: 28923573 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

NVP-BKM120; Trastuzumab; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

trialandresults.registries@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2013
• First Posted: March 22, 2013
• Study Start: September 3, 2013
• Primary Completion: February 18, 2015
• Study Completion: February 18, 2015
• Last Updated: November 14, 2019
• Results First Posted: November 14, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will share

Locations

DE (2); ES (2); AU (1)