STAR Cape+BKM120 MBC With Brain Met

NCT02000882 | Completed Phase 2 Results DMC

• 2 other identifiers: 11025CBKM120ZUS39T
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This is a study to determine the safety and effectiveness of BKM120 plus capecitabine in breast cancer patients with brain metastases. Both capecitabine and BMK120 have previously shown activity in patients with breast cancer. Like capecitabine, BMK120 is also effective in crossing the blood brain barrier making it a preferred candidate for its evaluation in patients with metastatic breast cancer (MBC).

Conditions

Brain Metastases; Breast Cancer; Metastatic Breast Cancer

Keywords

Breast Cancer; Triple Negative Breast Cancer; Brain Metastases; Capecitabine; Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Clinical Benefit Rate (CBR)

  CBR in the patients following WBRT or SRS or both will be the primary endpoint and is calculated as the total number of responders (CR or PR, assessed by RECIST 1.1) plus stable disease greater than or equal to 24 weeks (CR + PR + SD ≥ 24 weeks) divided by the total number of evaluable patients. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

  until disease progression (assessed by RECIST 1.1), unacceptable toxicity, death, or discontinuation from study for any other reason, up to 2 years from date of patient registration

Secondary Outcomes (4)

• Objective Response Rate (ORR)

  until disease progression (assessed by RECIST 1.1), unacceptable toxicity, death, or discontinuation from study for any other reason, up to 2 years from date of patient registration

• Median Time to Progression

  until disease progression (assessed by RECIST 1.1), unacceptable toxicity, death, or discontinuation from study for any other reason, up to 2 years from date of patient registration

• Median Overall Survival

  up to 2 years from date of patient registration

• Number of Treatment-related Serious AEs

  until disease progression (assessed by RECIST 1.1), unacceptable toxicity, death, or discontinuation from study for any other reason, up to 2 years from date of patient registration

Study Arms (1)

BKM120 plus Capecitabine

EXPERIMENTAL

BKM120 will be administered at a dose of 100 mg orally (PO) daily. Capecitabine will be administered at a dose of 1000 mg/m2 orally (PO) twice a day (rounded down to the nearest 500 mg pill) 14 days on and 7 days off. For patients with HER2+ MBC only, standard every 3-weekly trastuzumab (6 mg/kg IV) will be added to the capecitabine/BKM120.

Drug: BKM120; Drug: capecitabine; Drug: Trastuzumab

Interventions

BKM120 DRUG

Also known as: buparlisib

BKM120 plus Capecitabine

capecitabine DRUG

Also known as: Xeloda

BKM120 plus Capecitabine

Trastuzumab DRUG

Also known as: Herceptin

BKM120 plus Capecitabine

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years
• Female
• Histologically and/or cytologically confirmed diagnosis of inoperable metastatic breast cancer
• ER+/HER2- OR HER2+ OR triple-negative breast cancer, assessed as ER-, PgR-, and HER2-negative by local laboratory testing; HER2 negative status (based on most recently analyzed biopsy) is defined as IHC status of 0, 1+ or 2+ (if IHC 2+, a negative FISH test is required, ie, HER2 FISH ratio \< 2.0); ER-negative and PR-negative status is defined as ER and PgR \<10% nuclei positive by IHC. HER2-positive status is defined as 3+ staining in ≥10% of cells by immunohistochemistry or a HER2/CEP17 ratio ≥2 or an average of ≥6 HER2 gene copies per cell by in situ hybridization (ISH)
• At least one CNS lesion that is at least 5mm in size in at least one dimension in the setting of prior WBRT
• Prior WBRT is required and may have been administered at any time in patient's treatment history. Patients in the primary analysis will not have evidence of progression of disease following WBRT. However, patients whose brain metastases have progressed following WBRT are eligible. Patients must have completed WBRT at least 3 weeks prior to study entry.
• Prior SRS is allowed, but previous treatment of the 5mm target CNS lesion with SRS is not permitted
• ECOG performance status ≤ 2
• Adequate bone marrow function as shown by: ANC ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L, Hb \>9 g/dL
• Total calcium (corrected for serum albumin) within normal limits (biphosphonate use for malignant hypercalcemia control is not allowed)
• Magnesium ≥ the lower limit of normal
• Potassium within normal limits for the institution
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range (or ≤ 3.0 x upper limit of normal (ULN) if liver metastases are present)
• Serum bilirubin within normal range (or ≤ 1.5 x ULN if liver metastases are present; or total bilirubin ≤ 3.0 x ULN with direct bilirubin within normal range in patients with known Gilbert Syndrome)
• Serum creatinine ≤ 1.5 x ULN or 24-hour clearance ≥ 50 mL/min

You may not qualify if:

• Patient received prior treatment with a P13K inhibitor.
• Patient with known hypersensitivity to BKM120, capecitabine, or their excipients.
• Patient has evidence of impending herniation on baseline brain imaging.
• Patient has evidence of diffuse leptomeningeal disease on brain MRI or by previously documented CSF.
• Patient has acute or chronic liver, renal disease or pancreatitis (liver metastases are allowed)
• Patients has a mood disorder as judged by the Investigator or a psychiatrist, or as a result of patient's mood assessment questionnaire (PHQ-9 and/or GAD-7):
• 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) or patients with active severe personality disorders (defined according to DSM- IV) are not eligible. Note: for patients with psychotropic treatments ongoing at baseline, the dose and the schedule should not be modified within the previous 6 weeks prior to start of study drug.
• ≥ CTCAE grade 3 anxiety
• Meets the cut-off score of ≥ 12 in the PHQ-9 or a cut-off of ≥ 15 in the GAD-7 mood scale, respectively, or selects 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)
• Patients has diarrhea ≥ CTCAE grade 2
• Patients with uncontrolled hypertension defined as systolic blood pressure 170 or greater or diastolic blood pressure over 100.
• Patient has active cardiac disease including any of the following:
• Left ventricular ejection fraction (LVEF) \< 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO)
• QTc \> 480 msec on screening ECG (using the QTcF formula)
• Angina pectoris that requires the use of anti-anginal medication

Sponsors & Collaborators

• US Oncology Research: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

Please contact Zuzanne Bristow for list of sites

Multiple Locations, Texas, United States

Location

MeSH Terms

Conditions

Brain Neoplasms; Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

NVP-BKM120; Capecitabine; Trastuzumab

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Taqi Mohammad
• Organization: US Oncology Research

taqi.mohammad@mckesson.com

7138702175

Study Officials

• Joyce A. O'Shaughnessy, MD

  US Oncology Research, McKesson Specialty Health

  PRINCIPAL INVESTIGATOR

• Morris D. Groves, MD, JD

  US Oncology Research, McKesson Specialty Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2013
• First Posted: December 4, 2013
• Study Start: May 29, 2014
• Primary Completion: March 29, 2019
• Study Completion: March 29, 2019
• Last Updated: February 7, 2022
• Results First Posted: February 1, 2022

Record last verified: 2022-01

Locations

US (1)