Safety and Efficacy of BKM120 in Combination With Trastuzumab in Patients With Relapsing HER2 Overexpressing Breast Cancer Who Have Previously Failed Trastuzumab

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01132664
First received: May 7, 2010
Last updated: February 12, 2014
Last verified: February 2014
  Purpose

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 who have previously failed trastuzumab.


Condition Intervention Phase
Metastatic Breast Cancer
Trastuzumab
BKM120
HER2+
Drug: BKM120
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase Ib/II, Open Label, Multi-center Study Evaluating the Safety and Efficacy of BKM120 in Combination With Trastuzumab in Patients With Relapsing HER2 Overexpressing Breast Cancer Who Have Previously Failed Trastuzumab

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Adverse event frequencies by patient and DLT frequencies by cohort [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Number of patients with an objective response after at least two cycles of therapy [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Enrollment: 69
Study Start Date: May 2010
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: HER2+ metastatic breast cancer
Patients with HER2-overexpressing metastatic breast cancer, with or without PIK3 signaling pathway alteration, who have previously failed trastuzumab
Drug: BKM120
Experimental: 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
Drug: BKM120

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

// 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01132664

  Show 27 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01132664     History of Changes
Other Study ID Numbers: CBKM120X2107, 2009-015417-46
Study First Received: May 7, 2010
Last Updated: February 12, 2014
Health Authority: United States: Food and Drug Administration
Spain: Ministry of Health

Keywords provided by Novartis:
HER2
BKM120
PIK3
metastatic breast cancer
brain metastases
Herceptin
trastuzumab
capecitabine
open-label
maximum tolerated dose
Phase I

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Trastuzumab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 11, 2014