A Trial of BKM120 (a PI3K Inhibitor) in Patients With Triple Negative Metastatic Breast Cancer

NCT01629615 | Completed Phase 2 Results DMC

• 2 other identifiers: CBKM120ZES02T/SOLTI-11032011-006083-45
• Study Type: interventional
• Target: 50
• Locations: 2 countries
• Sites: 7

Brief Summary

The purpose of this study is to evaluate the clinical activity of BKM120 in patients with metastatic triple-negative breast cancer.

Conditions

Breast Cancer

Keywords

breast cancer; metastatic; triple negative breast cancer; BKM120; SOLTI; PI3K inhibitor

Outcome Measures

Primary Outcomes (1)

• Rate of Clinical Benefit

  Clinical benefit rate (CBR) was defined as the percentage of participants achieving complete response (CR), partial response (PR), or stable disease (SD) for 4 months or longer based on RECIST 1.1 criteria on treatment. Per RECIST 1.1 for target lesions: CR is the complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PD is at least a 20% increase in sum LD of target lesions (smallest sum LD reference), new lesions, and/or unequivocal progression of existing non-target lesions. Stable disease (SD) is defined as any condition not meeting the above criteria.

  Disease was evaluated radiologically at baseline and every 2 cycles on treatment then every 3 months up to 2 years. Participants in this study cohort were followed for response on average approximately 2 months.

Secondary Outcomes (3)

• Progression-free Survival

  Disease was evaluated radiologically at baseline and every 2 cycles on treatment then every 3 months up to 2 years. Participants in this study cohort were followed for PFS on average approximately 2 months.

• Overall Survival

  2 years

• Frequency and Severity of Adverse Events

  Adverse events (AEs) were assessed every 2 weeks for the first 2 cycles and every cycle thereafter. Participants were followed for AEs on average approximately 2 months.

Study Arms (1)

BKM120

EXPERIMENTAL

Drug: BKM120

Interventions

BKM120 DRUG

BKM120 oral capsules. 100 mg daily in cycles of 28 days, until disease progression

BKM120

Eligibility Criteria

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

You may qualify if:

• Pathologically and radiologically confirmed metastatic TNBC (Stage IV disease), previously documented by histological analysis, which is ER-negative and PR-negative by IHC and HER2 negative by IHC or FISH/CISH.
• Subjects must have received maximum two prior chemotherapy regimens for metastatic breast cancer.
• Availability of a representative tumor specimen (primary or metastasis, archival tissue or fresh biopsy for patients with biopsiable tumor) at baseline.
• At least one measurable lesion by RECIST 1.1
• Age ≥ 18 years at the day of consenting to the study
• ECOG performance status ≤ 2
• Adequate bone marrow and organ function as defined by the following laboratory values: ANC ≥ 1.0 x 109/L, platelets ≥ 100 x 109/L, hemoglobin ≥ 9.0 g/dL, INR ≤ 2; serum potassium between 3.0mmol/L and 5.5 mmol/L; Corrected serum calcium between8.0mg/dL and 11.5mg/dL (OR between 1.0mmol/L and 1.5mmol/L of Ionized calcium); serum magnesium between 1.2mg/dL and 3.0 mg/dL; serum creatinine ≤ 1.5 x ULN, ALT and AST within normal range (or ≤ 3.0 x 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 well documented Gilbert Syndrome); fasting plasma glucose (FPG) ≤ 140 mg/dL or ≤ 7.8 mmol/L.

You may not qualify if:

• Previous treatment with PI3K inhibitors
• Symptomatic CNS metastases
• Patients with controlled and asymptomatic CNS metastases may participate in this trial. As such, the patient must have completed any prior treatment for CNS metastases \> 28 days (including radiotherapy and/or surgery) prior to enrollment in this study. Patients with previously treated brain metastases, who are on a stable low dose corticosteroids treatment are eligible
• Concurrent malignancy or malignancy within 3 years of study enrollment (with the exception of adequately treated basal or squamous cell carcinoma or non-melanomatous skin cancer). An exception to this rule are those patients with documented germline mutations in BRCA1 or 2, who may have previous history of cancer
• Any of the following mood disorders as judged by the Investigator or a Psychiatrist, or meets the cut-off score of ≥ 10 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 ideation in the PHQ-9 (independent of the total score of the PHQ-9)
• Patients with a history or active episodes of major depression, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, history of suicide attempts or suicidal thoughts (eg. Risk of hurting or harming others) or patients with severe personality disorders (as defined by the DSM-IV) are not eligible. Note: For patients who are treated with psychotropic drugs at baseline, the dose and schedule shall not be changed during the 6 weeks prior to initiation of treatment with the study drug.
• ≥ CTCAE v 4.0 grade 3 anxiety
• Patients on concurrent use of other approved or investigational antineoplastic and / or chemotherapy or any continuous or intermittent treatment with therapeutic agents of low molecular weight (excluding monoclonal antibodies) in ≤ 21 days prior to enrollment in this study or who have not recovered from the effects such therapy will not be eligible.
• Radiotherapy ≤ 28 days prior to enrollment in this study or failure to recover from side effects of such therapy at the time of initiation of screening procedures.
• Major surgery within 28 days prior to starting study drug or has not recovered from major side effects of the surgery
• Poorly controlled diabetes mellitus (HbA1c \> 8%)
• 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)Note: ECHO/MUGA is only required at baseline if patient has a history of abnormal cardiac test results
• QTc \> 480 msec on screening ECG (using the QTcF formula
• Angina pectoris that requires the use of anti-anginal medication

Sponsors & Collaborators

• SOLTI Breast Cancer Research Group: lead
• Novartis Pharmaceuticals: collaborator
• Dana-Farber Cancer Institute: collaborator
• Stand Up To Cancer: collaborator

Study Sites (7)

Dana-Farber at Faulkner Hospital

Boston, Massachusetts, 02130, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Hospital Universitario Vall d´Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Instituto Valenciano de Oncología

Valencia, 46009, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

Location

Related Publications (2)

• Saura C, Lin N, Ciruelos E, Lluch A, Gavilá J, Winer E, Baselga J, Rodón J. A phase II, non-randomized, multicenter, exploratory trial of single agent BKM120 in patients with triple-negative metastatic breast cancer. Poster session presented at: 35th Annual San Antonio Breast Cancer Symposium (SABCS); 2012 December 4th-8th; San Antonio, Texas, United States.

  BACKGROUND

• Garrido-Castro AC, Saura C, Barroso-Sousa R, Guo H, Ciruelos E, Bermejo B, Gavila J, Serra V, Prat A, Pare L, Celiz P, Villagrasa P, Li Y, Savoie J, Xu Z, Arteaga CL, Krop IE, Solit DB, Mills GB, Cantley LC, Winer EP, Lin NU, Rodon J. Phase 2 study of buparlisib (BKM120), a pan-class I PI3K inhibitor, in patients with metastatic triple-negative breast cancer. Breast Cancer Res. 2020 Nov 2;22(1):120. doi: 10.1186/s13058-020-01354-y.

  PMID: 33138866 DERIVED

Related Links

• SOLTI Breast Cancer Research Group

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis; Triple Negative Breast Neoplasms

Interventions

NVP-BKM120

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Scientific Manager
• Organization: SOLTI

pamela.celiz@gruposolti.org

(+34) 93 343 63 02

Study Officials

• Jose Baselga, MD

  Massachusetts General Hospital

  STUDY CHAIR

• Eric Winer, MD

  Dana-Farber Cancer Institute

  STUDY CHAIR

• Jordi Rodon, MD

  Hospital Universitario Vall d´Hebron

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: May 23, 2012
• First Posted: June 27, 2012
• Study Start: June 1, 2012
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: October 28, 2020
• Results First Posted: October 28, 2020

Record last verified: 2020-10

Locations

ES (4); US (3)