BKM120 and Fulvestrant for Treating Postmenopausal Patients With Estrogen Receptor-Positive Stage IV Breast Cancer

NCT01339442 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 201105445NCI-2011-00583
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial will determine the Maximum Tolerated Dose (MTD) of BKM120 when given together with fulvestrant in treating postmenopausal patients with estrogen receptor-positive (ER+) stage IV breast cancer. The toxicity profile of this combination therapy will also be described. Inhibition of PI3K by BKM120 may enhance programmed cell death (apoptosis) in estrogen receptor positive (ER+) breast cancer cells. Giving fulvestrant together with BKM 120 may enhance this apoptotic effect, providing a novel therapeutic strategy for patients with metastatic ER+ breast cancer.

Conditions

Estrogen Receptor-positive Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer

Outcome Measures

Primary Outcomes (2)

• MTD of BKM120 in combination with fulvestrant

  Highest dose level at which no more than 1 of 6 patients develops a dose-limiting toxicity

  28 days (completion of cycle 1)

• Number of participants with adverse events after treatment with BKM120 in combination with fulvestrant

  28 days after completion of treatment

Secondary Outcomes (7)

• Anti-tumor effect (PR, CR, SD and PD) of BKM120 in combination with fulvestrant

  End of treatment (approximately 3 months)

• Steady state blood concentration of BKM120

  Baseline, Cycle 2 Day 1, Cycle 3 Day 1

• Tumor PI3K pathway abnormalities in tissue from previous biopsy or collected at baseline

  Baseline

• Effects of study therapy on blood levels of fasting C-peptide

  Baseline, Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1

• Effects of study therapy on blood levels of glucose

  Baseline, Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 15, Cycle 3 Day 1, End of Treatment

Other Outcomes (1)

• FLT-PET/CT effect of BKM120 on tumor cell proliferation

  18 days

Study Arms (4)

Dose Level 1 - Phase 1A

EXPERIMENTAL

BKM120 80 mg PO daily. Fulvestrant 500 mg IM on Days 1 \& Day 15 during Cycle 1 then on Day 1 of each subsequent cycle.

Drug: BKM120; Drug: Fulvestrant; Procedure: biopsy

Dose Level 2 - Phase IA

EXPERIMENTAL

BKM120 100 mg PO daily. Fulvestrant 500 mg IM on Days 1 \& Day 15 during Cycle 1 then on Day 1 of each subsequent cycle.

Drug: BKM120; Drug: Fulvestrant; Procedure: biopsy

Phase IB

EXPERIMENTAL

BKM120 (dose to be determined in Phase IA)PO 5 days on/ 2 days off per week. Fulvestrant 500 mg IM on Days 1 \& Day 15 during Cycle 1 then on Day 1 of each subsequent cycle.

Drug: BKM120; Drug: Fulvestrant; Procedure: biopsy

Cohort C

EXPERIMENTAL

BKM120 (dose determined in Phase IA) PO daily. Fulvestrant 500 mg IM on Day 1 and Day 15 during Cycle 1 then monthly on Day 1 of subsequent cycles.

Drug: BKM120; Drug: Fulvestrant; Procedure: biopsy

Interventions

BKM120 DRUG

Also known as: PI3K_Inhibitor_BKM120

Cohort C; Dose Level 1 - Phase 1A; Dose Level 2 - Phase IA; Phase IB

Fulvestrant DRUG

Also known as: Faslodex, ICI 182,780

Cohort C; Dose Level 1 - Phase 1A; Dose Level 2 - Phase IA; Phase IB

biopsy PROCEDURE

Correlative studies

Also known as: biopsies

Cohort C; Dose Level 1 - Phase 1A; Dose Level 2 - Phase IA; Phase IB

Eligibility Criteria

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

You may qualify if:

• Patient must be ≥ 18 years of age
• Patient must be a postmenopausal woman, defined by one of the following criteria:
• Women ≥ 60 years
• Women aged 45-59 years with spontaneous cessation of menses ≥ 12 months prior to registration
• Women aged 45-59 years with cessation of menses of duration \< 12 months or secondary to hysterectomy AND an follicle-stimulating hormone (FSH) level in the postmenopausal range according to institutional standards (or \> 34.4 IU/L if institutional range is not available) prior to registration
• Women aged 45-59 years on hormonal replacement therapy who have discontinued hormonal therapy AND an FSH level in the postmenopausal range according to institutional standards (or \> 34.4 IU/L if institutional range is not available) prior to registration
• Status post bilateral surgical oophorectomy
• Patient must have a negative serum pregnancy test within 48 hours before starting study treatment (if a woman of childbearing potential)
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status =\< 2
• Patient must have histologically or cytologically confirmed invasive breast cancer that is stage IV or metastatic (histologic/cytologic confirmation of recurrence preferred, but not required)
• Patient must have a representative tumor tissue specimen available; archival tissue is allowed
• Either the primary or the metastatic tumor must be positive for estrogen receptor (\>= 1% tumor cell staining by immunohistochemistry or an Allred Score of \>= 3 by immunohistochemistry)
• Patient must have at least one site of measurable disease as per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria
• Patient must have had no more than 3 lines of systemic therapy (including endocrine therapy) for metastatic disease to be eligible for phase IB and the last 10 patients of Cohort C; there is no limitation on the numbers of prior systemic therapies for phase IA and the first 2 patients of Cohort C
• Patients who are currently taking fulvestrant without disease progression are eligible

You may not qualify if:

• Patient must not have received prior treatment with a P13K inhibitor
• Patient must not have a known hypersensitivity to BKM120 or to its excipients
• Patient must not have untreated brain metastases; however, patients with metastatic central nervous system (CNS) tumors may participate in this trial if the patient is:
• weeks from therapy completion (including radiation and/or surgery)
• Clinically stable at the time of study entry
• Not receiving corticosteroid therapy
• Patient must not have acute or chronic liver disease, renal disease, or pancreatitis
• Patient must not have any of the following mood disorders as judged by the Investigator or a Psychiatrist
• 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 (immediate risk of doing harm to others)
• Greater than or equal to Common Terminology Criteria for Adverse Events (CTCAE) grade 3 anxiety
• Patient must not meet the cut-off score of \>= 10 in the Patient Health Questionnaire (PHQ-9) or a cut-off of \>= 15 in the Generalized Anxiety Disorder (GAD)-7 mood scale, respectively, or select a positive response of 1, 2, or 3 to question number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of the total score of the PHQ-9)
• Patient must not have \>= grade 2 diarrhea
• Patient must not have active cardiac disease including any of the following:
• Left ventricular ejection fraction (LVEF) \< 50% as determined by Multiple Grated acquisition (MUGA) scan or echocardiogram (ECHO)
• QTc \> 480 msec on screening electrocardiogram (ECG) (using the QTcF formula)

Sponsors & Collaborators

• Washington University School of Medicine: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Breast Neoplasms

Interventions

NVP-BKM120; Fulvestrant; Biopsy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Cynthia Ma

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2011
• First Posted: April 20, 2011
• Study Start: November 14, 2011
• Primary Completion: December 21, 2016
• Study Completion: December 28, 2016
• Last Updated: January 25, 2017

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)