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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT01132664
Other study ID # CBKM120X2107
Secondary ID 2009-015417-46
Status Terminated
Phase Phase 1/Phase 2
First received May 7, 2010
Last updated September 29, 2015
Start date May 2010
Est. completion date August 2014

Study information

Verified date September 2015
Source Novartis
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug AdministrationBelgium: Federal Agency for Medicinal Products and Health ProductsFrance: Agence nationale de sécurité du médicament et des produits de santé (ANSM)Italy: The Italian Medicines AgencySpain: Ministry of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Terminated
Enrollment 72
Est. completion date August 2014
Est. primary completion date August 2014
Accepts healthy volunteers No
Gender Both
Age group 18 Years and older
Eligibility 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

|| Specific Inclusion Criteria for patients in BM cohorts:

- 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

|| Specific Exclusion Criteria for patients in BM cohorts

- Prior treatment with capecitabine

- Patient has known dihydropyrimidine dehydrogenase (DPD) deficiency

- Patient is currently receiving treatment with EIAED

- Other protocol-defined inclusion/exclusion criteria may apply

Study Design

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Intervention

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

Locations

Country Name City State
Belgium Novartis Investigative Site Liege
Belgium Novartis Investigative Site Wilrijk
France Novartis Investigative Site Lyon Cedex
France Novartis Investigative Site Saint-Herblain Cédex
Italy Novartis Investigative Site Cagliari CA
Italy Novartis Investigative Site Macerata MC
Italy Novartis Investigative Site Modena MO
Italy Novartis Investigative Site Terni TR
Spain Novartis Investigative Site Barcelona Catalunya
Spain Novartis Investigative Site Hospitalet de LLobregat Catalunya
Spain Novartis Investigative Site Valencia Comunidad Valenciana
United Kingdom Novartis Investigative Site Brighton East Sussex
United Kingdom Novartis Investigative Site Nottingham
United Kingdom Novartis Investigative Site Oxford
United States University of Alabama at Birmingham/ Kirklin Clinic Univ AL - PI Birmingham Alabama
United States Karmanos Cancer Institute Dept.of KarmanosCancerInst (6) Detroit Michigan
United States Highlands Oncology Group Dept of Highlands Oncology Grp Fayetteville Arkansas
United States Sarah Cannon Research Institute Sarah Cannon Cancer Center SC Nashville Tennessee
United States Beth Israel Medical Center BIMC New York New York
United States Washington University School Of Medicine-Siteman Cancer Ctr WA Siteman St. Louis Missouri
United States H. Lee Moffitt Cancer Center & Research Institute Tampa Florida

Sponsors (1)

Lead Sponsor Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Belgium,  France,  Italy,  Spain,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 Yes
Primary 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 No
Secondary Disease Control Rate (DCR) Based on Investigator Assessment- Phase l & ll Disease control rate (DCR) is the rate of patients with BOR equal to CR, PR, or stable disease (SD) as per RECIST criteria.
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 No
Secondary Clinical Benefit Rate (CBR) - Phase l & ll CBR is patients with CR, PR or stable disease (SD) = 24 weeks according to RECIST by the investigator.
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 No
Secondary Progression Free Survival (PFS) - Based on Investigator Review Using Kaplan Meier - Phase l & ll. PFS Was Analyzed Only in Patients With Known PIK3 Status, Thus Only 26/50 Patients Were Analyzed. 18 months No
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