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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02404844
Recruitment Status : Completed
First Posted : April 1, 2015
Last Update Posted : April 20, 2018
Sponsor:
Collaborators:
iOMEDICO AG
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Anja Welt, University Hospital, Essen

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.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: BKM120 Drug: Tamoxifen Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 48 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Molecularly Stratified Parallel Cohort, Single Arm Phase II Trial of the Phosphoinositide 3-kinase (PI3K) Inhibitor Buparlisib (BKM120) in Combination With Tamoxifen in Patients With Hormone Receptor-positive, HER2-negative Inoperable (Locally Advanced or Metastatic) Breast Cancer With Prior Exposure to Antihormonal Therapy
Study Start Date : December 2014
Actual Primary Completion Date : September 19, 2017
Actual Study Completion Date : October 19, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: 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

Drug: BKM120
daily oral
Other Name: Buparlisib

Drug: Tamoxifen
daily oral




Primary Outcome Measures :
  1. Progression free survival (PFS)-rate in the full population, after 6 months [ Time Frame: 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


Secondary Outcome Measures :
  1. Progression free survival (PFS)- rate in the subpopulations after 6 months of combination therapy [ Time Frame: 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

  2. Progression-free survival (PFS) [ Time Frame: 6 months ]
    PFS in subpopulations and full population. 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

  3. 1 year overall survival (OS) rate [ Time Frame: 1 year ]
    OS is defined as time from date of start of treatment to the date of death from any cause.

  4. 2 years overall survival (OS) rate [ Time Frame: 2 years ]
    OS is defined as time from date of start of treatment to the date of death from any cause.

  5. Overall response rate (ORR) [ Time Frame: 6 months ]
    ORR is defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) (RECIST v1.1).

  6. Disease control rate (DCR) [ Time Frame: 6 months ]
    DCR is defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) or stable disease (SD) lasting more than 12 weeks (RECIST v1.1).

  7. Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: From date of informed consent to +30 days from last application of study medication ]
    Type, frequency and severity of adverse events per CTCAE v4.03

  8. Incidence and severity of depressive episodes during the course of treatment [ Time Frame: From date of informed consent to +30 days from last application of study medication ]
    Change in depressive episodes assessed by PHQ-9 questionnaire

  9. Incidence and severity of depressive episodes during the course of treatment [ Time Frame: From date of informed consent to +30 days from last application of study medication ]
    Change in depressive episodes assessed by GAD-7 questionnaire


Other Outcome Measures:
  1. 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. [ Time Frame: 2 years ]
    Finding 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. Validation of a proprietary technology for highly sensitive and specific mutation detection of circulating free tumor DNA [ Time Frame: 2 years ]
    Finding of specific mutation detection of circulating free tumor DNA



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02404844


Locations
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Germany
iOMEDICO AG
Freiburg, Baden-Württemberg, Germany, 79108
Sponsors and Collaborators
University Hospital, Essen
iOMEDICO AG
Novartis Pharmaceuticals
Investigators
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Principal Investigator: Anja Welt, MD University Hospital, Essen
Publications:
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Responsible Party: Anja Welt, Principal Investigator, University Hospital, Essen
ClinicalTrials.gov Identifier: NCT02404844    
Other Study ID Numbers: iOM-02282
2014-000599-24 ( EudraCT Number )
CBKM120ZDE02T ( Other Grant/Funding Number: Novartis Pharma GmbH )
AIO-MAM-0114/ass ( Other Grant/Funding Number: AIO )
First Posted: April 1, 2015    Key Record Dates
Last Update Posted: April 20, 2018
Last Verified: April 2018
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Tamoxifen
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Bone Density Conservation Agents