Phase 1b/2 Study of BKM120 Plus Trastuzumab in Patients With HER2-positive Breast Cancer

NCT01132664 | Terminated Phase 1 Results

• 2 other identifiers: CBKM120X21072009-015417-46
• Study Type: interventional
• Target: 72
• Locations: 6 countries
• Sites: 21

Brief Summary

This study will assess the safety and efficacy of BKM120 in combination with trastuzumab in patients with relapsing HER2 overexpressing breast cancer who have previously failed trastuzumab. The study will further assess the safety and preliminary efficacy of BKM120 in combination with trastuzumab and capecitabine in patients with relapsing HER2 overexpressing breast cancer and brain metastases (BM) who have previously failed trastuzumab.

Conditions

Metastatic Breast Cancer; HER2+ Breast Cancer

Keywords

HER2; BKM120; PIK3; metastatic breast cancer; brain metastases; Herceptin; trastuzumab; capecitabine; open-label; maximum tolerated dose; Phase I/Phase ll

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicity (DLT) - Phase l Only

  Determination of the maximum tolerated dose (MTD) in the dose escalation part of the study was based upon the estimation of the probability of DLT in Cycle 1 in patients of the dose-determining set.

  cycle 1 - 28 days

• Overall Response Rate (ORR) - Phase ll

  Objective response rate (ORR) was defined as the rate of patients with best overall response (BOR) equal to complete response (CR) or partial response (PR) according to RECIST 1.0 from the Investigators review. Per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0 assessed of the disease status by imaging (i.e. CT/MRI): Complete Response (CR) = Disappearance of all tumor lesions; Partial Response (PR)= \>=30% shrinkage of lesions; Overall Response (OR) = patients with CR and PR.

  18 months

Secondary Outcomes (3)

• Disease Control Rate (DCR) Based on Investigator Assessment- Phase l & ll

  18 months

• Clinical Benefit Rate (CBR) - Phase l & ll

  18 months

• Progression Free Survival (PFS) - Based on Investigator Review Using Kaplan Meier - Phase l & ll

  18 months

Study Arms (2)

HER2+ metastatic breast cancer

EXPERIMENTAL

Patients with HER2-overexpressing metastatic breast cancer, with or without PIK3 signaling pathway alteration, who have previously failed trastuzumab

Drug: BKM120; Drug: Trastuzumab

HER2+ metastatic breast cancer with BM

EXPERIMENTAL

Patients with HER2-overexpressing metastatic breast cancer and brain metastases, with or without PIK3 signaling pathway alteration, who have previously failed trastuzumab

Drug: BKM120; Drug: Trastuzumab; Drug: Capecitabine

Interventions

BKM120 DRUG

Buparlisib (BKM120) is the investigational drug. Burparlisib was supplied as 10 mg and 50 mg hard gelatin capsules. Buparlisib was dosed on a flat scale of mg/day and not adjusted to body weight or body surface area. Buparlisib capsules were packaged in high density polyethylene bottles with a plastic child resistant closure.

HER2+ metastatic breast cancer; HER2+ metastatic breast cancer with BM

Trastuzumab DRUG

Trastuzumab was used in this study according to the local regulations in each participating country. A loading dose (4 mg/kg) of trastuzumab was administered (if required as assessed by the principal Investigator based on the timing of the last trastuzumab dose prior to enrollment) on Day -7 over 90 minutes, followed by weekly intravenous infusion of 2 mg/kg maintenance doses from Day 1 of Cycle 1 (over 30 minutes if the previous infusion was well tolerated).

HER2+ metastatic breast cancer; HER2+ metastatic breast cancer with BM

Capecitabine DRUG

1000 mg/m2 twice a day from day 1 to Day 14 of a 21-day cycle.

HER2+ metastatic breast cancer with BM

Eligibility Criteria

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

You may qualify if:

• World Health Organization (WHO) Performance Status of ≤ 2
• Patients with HER2+ breast cancer by local laboratory testing (immunohistochemistry \[IHC\] 3+ staining or fluorescence in situ hybridization \[FISH\] confirmation for IHC 2+ and 1+)
• Documented tumor resistance to trastuzumab:
• Recurrence while on trastuzumab or within 12 months since the last infusion for patients who received trastuzumab as adjuvant treatment
• Progression while on or within 4 weeks since the last infusion of trastuzumab for patients who received trastuzumab for metastatic disease.
• Documented evidence of progressive disease per Response Evaluation Criteria in Solid Tumors (RECIST) on trastuzumab-based therapy defined as:
• Phase Ib: at any time before study entry
• Phase II: within 16 weeks before date of first dosing
• Received at least 1 but no more than 4 prior anit-HER2 based regimens including at least 1 regimen containing trastuzumab (adjuvant or neo-adjuvant trastuzumab will be considered as one prior regimen). HER2 directed therapies are defined as comprising trastuzumab, lapatinib, and trastuzumab-DM1 (T-DM1) only.
• Phase II only: trastuzumab, T-DM1 or lapatinib must be part of the most recent line of therapy
• Previous lines of cytotoxic chemotherapy:
• Phase Ib: no more than 4 lines of cytotoxic chemotherapy
• Phase II: no more than 3 lines of cytotoxic chemotherapy
• Measurable disease:
• Phase Ib: patient has at least one measurable lesion or non-measurable disease as defined per RECIST

You may not qualify if:

• Patients with untreated brain metastases
• Patients with acute or chronic liver, renal disease or pancreatitis
• Patients with any peripheral neuropathy ≥ Common Terminology Criteria for Adverse Events (CTCAE) grade 2
• Patients with a history of mood disorders or ≥ CTCAE grade 3 anxiety
• Patient with clinical manifest diabetes mellitus or steroid-induced diabetes mellitus
• Prior treatment with capecitabine
• Patient has known dihydropyrimidine dehydrogenase (DPD) deficiency
• Patient is currently receiving treatment with EIAED

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (21)

University of Alabama at Birmingham/ Kirklin Clinic Univ AL - PI

Birmingham, Alabama, 35294-0006, United States

Location

Highlands Oncology Group Dept of Highlands Oncology Grp

Fayetteville, Arkansas, 72703, United States

Location

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

Karmanos Cancer Institute Dept.of KarmanosCancerInst (6)

Detroit, Michigan, 48201, United States

Location

Washington University School Of Medicine-Siteman Cancer Ctr WA Siteman

St Louis, Missouri, 63110, United States

Location

Beth Israel Medical Center BIMC

New York, New York, 10003, United States

Location

Sarah Cannon Research Institute Sarah Cannon Cancer Center SC

Nashville, Tennessee, 37203, United States

Location

Novartis Investigative Site

Liège, 4000, Belgium

Location

Novartis Investigative Site

Wilrijk, 2610, Belgium

Location

Novartis Investigative Site

Lyon, 69373, France

Location

Novartis Investigative Site

Saint-Herblain Cédex, 44805, France

Location

Novartis Investigative Site

Cagliari, CA, 09134, Italy

Location

Novartis Investigative Site

Macerata, MC, 62100, Italy

Location

Novartis Investigative Site

Modena, MO, 41100, Italy

Location

Novartis Investigative Site

Terni, TR, 05100, Italy

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

L'Hospitalet de Llobregat, Catalonia, 08907, Spain

Location

Novartis Investigative Site

Valencia, Valencia, 46010, Spain

Location

Novartis Investigative Site

Brighton, East Sussex, BN2 5BE, United Kingdom

Location

Novartis Investigative Site

Nottingham, NG5 1PB, United Kingdom

Location

Novartis Investigative Site

Oxford, OX3 7LJ, United Kingdom

Location

MeSH Terms

Conditions

Breast Neoplasms; Brain Neoplasms

Interventions

NVP-BKM120; Trastuzumab; Capecitabine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

trialandresults.registry@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 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2010
• First Posted: May 28, 2010
• Study Start: May 1, 2010
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: August 17, 2016
• Results First Posted: October 30, 2015

Record last verified: 2016-08

Locations

ES (3); BE (2); FR (2); US (7); GB (3); IT (4)