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

NCT ID: NCT01132664

Last Updated: 2016-08-17

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-05-31
• Study Completion Date: 2014-08-31

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

HER2+ metastatic breast cancer

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

Group Type: EXPERIMENTAL

BKM120

Intervention Type: 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.

Trastuzumab

Intervention Type: 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 with BM

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

Group Type: EXPERIMENTAL

BKM120

Intervention Type: 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.

Trastuzumab

Intervention Type: 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).

Capecitabine

Intervention Type: DRUG

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

Interventions

BKM120

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.

Intervention Type: DRUG

Trastuzumab

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).

Intervention Type: DRUG

Capecitabine

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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
• Phase II: patient has at least one measureable lesion as defined per RECIST

• Patient has evidence of progressing brain metastases and/or new metastatic brain lesion(s) without leptomeningeal disease.
• Patient has received prior WBRT and/or SRS at at >28 and >/= 14 days, respectively, prior to starting study drug and the patient must have recovered from the side effects of the therapy
• WHO performance status of </=1
• PT INR </= 1.5
• Any number of prior HER2-directed and cytotoxic regimens, and the most recent line may be any type of anti-neoplastic therapy

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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

Birmingham, Alabama, United States

Highlands Oncology Group Dept of Highlands Oncology Grp

Fayetteville, Arkansas, United States

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, United States

Karmanos Cancer Institute Dept.of KarmanosCancerInst (6)

Detroit, Michigan, United States

Washington University School Of Medicine-Siteman Cancer Ctr WA Siteman

St Louis, Missouri, United States

Beth Israel Medical Center BIMC

New York, New York, United States

Sarah Cannon Research Institute Sarah Cannon Cancer Center SC

Nashville, Tennessee, United States

Novartis Investigative Site

Liège, , Belgium

Novartis Investigative Site

Wilrijk, , Belgium

Novartis Investigative Site

Lyon, , France

Novartis Investigative Site

Saint-Herblain Cédex, , France

Novartis Investigative Site

Cagliari, CA, Italy

Novartis Investigative Site

Macerata, MC, Italy

Novartis Investigative Site

Modena, MO, Italy

Novartis Investigative Site

Terni, TR, Italy

Novartis Investigative Site

Barcelona, Catalonia, Spain

Novartis Investigative Site

L'Hospitalet de Llobregat, Catalonia, Spain

Novartis Investigative Site

Valencia, Valencia, Spain

Novartis Investigative Site

Brighton, East Sussex, United Kingdom

Novartis Investigative Site

Nottingham, , United Kingdom

Novartis Investigative Site

Oxford, , United Kingdom

Countries

United States; Belgium; France; Italy; Spain; United Kingdom

Other Identifiers

2009-015417-46

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CBKM120X2107

Identifier Type: -

Identifier Source: org_study_id