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

NCT ID: NCT02404844

Last Updated: 2018-04-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-12-31
• Study Completion Date: 2017-10-19

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.

Detailed Description

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:

• PIK3CA mutation/preserved PTEN expression
• PIK3CA wildtype or mutation/ loss of PTEN expression
• PIK3CA wildtype/preserved PTEN expression. This trial will explore, if the combination of BKM120 and tamoxifen can overcome resistance to antihormonal therapies. BKM120 is selective for class I PI3K enzymes with no mTOR inhibitory activity that has entered Phase II and III clinical trials. The tumor suppressor PTEN is the most important negative regulator of the PI3K signaling pathway. Therefore, in addition the trial will prospectively evaluate PIK3CA mutations and/or loss of PTEN expression as predictive biomarkers for clinical benefit from combined treatment with BKM120 and tamoxifen.

Conditions

Breast Cancer

Study Design

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

Study Groups

BKM120 + Tamoxifen

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

Group Type: EXPERIMENTAL

BKM120

Intervention Type: DRUG

daily oral

Tamoxifen

Intervention Type: DRUG

daily oral

Interventions

BKM120

daily oral

Intervention Type: DRUG

Tamoxifen

daily oral

Intervention Type: DRUG

Other Intervention Names

Buparlisib

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

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

Sponsors

iOMEDICO AG

INDUSTRY

Sponsor Role: collaborator

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

University Hospital, Essen

OTHER

Sponsor Role: lead

Responsible Party

Anja Welt

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Anja Welt, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Essen

Locations

iOMEDICO AG

Freiburg im Breisgau, Baden-Wurttemberg, Germany

Countries

Germany

References

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.

Reference Type: BACKGROUND

PMID: 22162589 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 24652201 (View on PubMed)

Other Identifiers

2014-000599-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CBKM120ZDE02T

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

AIO-MAM-0114/ass

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

iOM-02282

Identifier Type: -

Identifier Source: org_study_id