Trial of BKM120/Tamoxifen-combination in Patients With HR-pos, HER2-neg Breast Cancer

NCT02404844 | Completed Phase 2

• 4 other identifiers: iOM-022822014-000599-24CBKM120ZDE02TAIO-MAM-0114/ass
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

This is a clinical trial with a molecularly stratified parallel cohort, single arm design to explore the efficacy and safety of BKM120 in combination with tamoxifen in patients with ER/PR-positive, HER2-negative breast cancer with prior exposure to antihormonal therapy, and different biomarker profiles, two of them potentially indicative of constitutive PI3K pathway activation.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS)-rate in the full population, after 6 months

  PFS is defined as time from date of start of treatment to the date of the event, defined as the first documented disease progression or death due to any cause per local investigator assessment

  6 months

Secondary Outcomes (9)

• Progression free survival (PFS)- rate in the subpopulations after 6 months of combination therapy

  6 months

• Progression-free survival (PFS)

  6 months

• 1 year overall survival (OS) rate

  1 year

• 2 years overall survival (OS) rate

  2 years

• Overall response rate (ORR)

  6 months

Other Outcomes (2)

• Identification of genomic signatures associated with clinical outcome in response to PI3K pathway-directed therapy with tamoxifen and buparlisib in ER/PR-positive breast cancer.

  2 years

• Validation of a proprietary technology for highly sensitive and specific mutation detection of circulating free tumor DNA

  2 years

Study Arms (1)

BKM120 + Tamoxifen

EXPERIMENTAL

BKM120 (Buparlisib): 100 mg/day, orally, on a continuous dosing schedule without interruption starting on day 1 in 28 day cycle Tamoxifen: 20 mg/day, orally, on a continuous dosing schedule without interruption starting on day 1 in 28 day cycle

Drug: BKM120; Drug: Tamoxifen

Interventions

BKM120 DRUG

daily oral

Also known as: Buparlisib

BKM120 + Tamoxifen

Tamoxifen DRUG

daily oral

BKM120 + Tamoxifen

Eligibility Criteria

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

You may qualify if:

• Patient has histologically and/or cytologically confirmed diagnosis of breast cancer
• Patient has radiologic or objective evidence of inoperable locally advanced, or metastatic breast cancer
• Patient has a known hormone receptor status HR-positive (ER and/or PR positive) and HER2-negative status
• Patient has a representative archival formalin-fixed tumor biopsy (metastasis or primary tumor)
• Patient has prior exposure to antihormonal therapy
• Patient has received ≤ 2 prior antihormonal treatments in the metastatic setting
• Prior treatment with tamoxifen in the (neo-)adjuvant setting is allowed but has to be discontinued for at least 1 year.
• Patient may have received up to one prior chemotherapy in the metastatic setting
• Measurable or non-measurable lesions according to RECIST v1.1 criteria
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 2

You may not qualify if:

• Patient has received previous treatment with a PI3K- or AKT-inhibitor or mTOR-inhibitors
• Prior treatment with Tamoxifen in the metastatic setting. Treatment with tamoxifen in the (neo-)adjuvant setting is allowed, but has to be discontinued for at least 1 year
• Patient has symptomatic CNS metastases
• Patient has a medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (e.g. risk of doing harm to self or others), or patients with active severe personality disorders (defined according to DSM-IV).
• Patient has a known history of HIV infection (testing not mandatory) infection

Sponsors & Collaborators

• University Hospital, Essen: lead
• iOMEDICO AG: collaborator
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

iOMEDICO AG

Freiburg im Breisgau, Baden-Wurttemberg, 79108, Germany

Location

Related Publications (2)

• Bendell JC, Rodon J, Burris HA, de Jonge M, Verweij J, Birle D, Demanse D, De Buck SS, Ru QC, Peters M, Goldbrunner M, Baselga J. Phase I, dose-escalation study of BKM120, an oral pan-Class I PI3K inhibitor, in patients with advanced solid tumors. J Clin Oncol. 2012 Jan 20;30(3):282-90. doi: 10.1200/JCO.2011.36.1360. Epub 2011 Dec 12.

  PMID: 22162589 BACKGROUND

• Rodon J, Brana I, Siu LL, De Jonge MJ, Homji N, Mills D, Di Tomaso E, Sarr C, Trandafir L, Massacesi C, Eskens F, Bendell JC. Phase I dose-escalation and -expansion study of buparlisib (BKM120), an oral pan-Class I PI3K inhibitor, in patients with advanced solid tumors. Invest New Drugs. 2014 Aug;32(4):670-81. doi: 10.1007/s10637-014-0082-9. Epub 2014 Mar 21.

  PMID: 24652201 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms

Interventions

NVP-BKM120; Tamoxifen

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Anja Welt, MD

  University Hospital, Essen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 20, 2015
• First Posted: April 1, 2015
• Study Start: December 1, 2014
• Primary Completion: September 19, 2017
• Study Completion: October 19, 2017
• Last Updated: April 20, 2018

Record last verified: 2018-04

Locations

DE (1)