Paclitaxel and BKM120 Before Surgery in Treating Patients With Stage II or III Estrogen Receptor-Positive and HER2-Negative Breast Cancer

NCT01953445 | Withdrawn Phase 2

• 1 other identifier: 201311126
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase II trial studies the effects of paclitaxel combined with phosphoinositide 3-kinase (PI3K) inhibitor BKM120 in patients with stage II or III breast cancer that is described as estrogen receptor-positive, human epidermal growth factor 2 (HER2)-negative and endocrine therapy resistant. Drugs such as paclitaxel stop the growth of tumors by blocking cancer cell division. PI3K inhibitor BKM120 inhibits some of the enzymes needed for cell growth and may improve the response of endocrine resistant tumors to treatment. Giving paclitaxel and PI3K inhibitor BKM120 before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Conditions

Breast Neoplasms

Outcome Measures

Primary Outcomes (1)

• Pathologic complete response rate in patients with endocrine therapy resistant tumors following neoadjuvant paclitaxel in combination with BKM120

  Proportion of patients with no histologic evidence of invasive tumor cells in the surgical breast specimen and axillary or lymph nodes. A 90% confidence interval for the pCR rate will be constructed using the Duffy-Santner approach.

  After 2-12 weeks on neoadjuvant endocrine therapy

Secondary Outcomes (2)

• Proportion of patients who developed severe (grade 3+) toxicity related to neoadjuvant treatment

  Up to 30 days after completion of study treatment

• Clinical response rate in patients with endocrine therapy resistant tumors following neoadjuvant paclitaxel in combination with BKM120

  Up to 12 weeks

Study Arms (1)

Treatment (PI3K inhibitor BKM120, paclitaxel)

EXPERIMENTAL

Patients receive PI3K inhibitor BKM120 PO QD on days 1-28 and paclitaxel IV over 60 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.

Drug: paclitaxel; Drug: BKM120

Interventions

paclitaxel DRUG

Also known as: Anzatax, Asotax, Bristaxol, Praxel, TAX, Taxol, Taxol Konzentrat

Treatment (PI3K inhibitor BKM120, paclitaxel)

BKM120 DRUG

Treatment (PI3K inhibitor BKM120, paclitaxel)

Eligibility Criteria

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

You may qualify if:

• Clinical stage II or III ER-positive, HER2-negative breast cancer with complete surgical excision of the breast cancer as the treatment goal.
• Tumor size at least 2cm in one dimension by clinical or radiographic examination (WHO criteria).
• Received at least 2 weeks of neoadjuvant endocrine therapy.
• Ki67 after 2 to 12 weeks of neoadjuvant endocrine therapy is \> 10% confirmed by central testing at Washington University.
• At least 18 years of age.
• ECOG performance status ≤ 2
• Normal bone marrow and organ function as defined below:
• Absolute neutrophil count ≥ 1,500/mcl
• Platelets ≥ 100,000/mcl
• Hemoglobin \> 9.0 g/dL
• AST(SGOT)/ALT(SGPT) \<= IULN
• Serum bilirubin within normal limits (OR total bilirubin ≤ 3.0 x IULN with direct bilirubin within normal range in patients with well documented Gilbert Syndrome)
• Creatinine ≤ 1.5 x IULN OR Creatinine clearance ≥ 50 mL/min/1.73 m2
• plasma glucose ≤ 120 mg/dL (6.7 mmol/L)
• Patient may be pre- or post-menopausal. Women of childbearing potential must agree to use adequate contraception prior to study entry, for the duration of study participation, and for up to 30 days following completion of treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.

You may not qualify if:

• Prior therapy with a PI3K inhibitor for the indexed breast cancer.
• Sentinel lymph node dissection prior to neoadjuvant therapy.
• Currently receiving any other investigational agents.
• Acute or chronic liver disease, renal disease, or pancreatitis.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to BKM120 or paclitaxel or other agents used in the study.
• Presence of one of the following mood disorders (as judged by the physician or a psychiatrist or as a result of the patient's mood assessment questionnaire):
• Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, or a history of suicidal attempt/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)
• CTCAE grade 2 diarrhea.
• Presence of active cardiac disease, including any of the following:
• Left ventricular ejection fraction (LVEF) \< 50% as determined by MUGA or echocardiogram
• QTC \> 480 msec on screening ECG (using the QTcF formula)
• Angina pectoris that requires the use of anti-anginal medication
• Ventricular arrhythmias except for benign premature ventricular contractions

Sponsors & Collaborators

• Washington University School of Medicine: lead

Related Links

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

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Paclitaxel; Taxes; NVP-BKM120

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations

Study Officials

• Foluso Ademuyiwa, M.D., M.P.H.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

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: September 19, 2013
• First Posted: October 1, 2013
• Study Start: August 1, 2014
• Primary Completion: June 1, 2015
• Study Completion: July 1, 2015
• Last Updated: December 8, 2014

Record last verified: 2014-12