Study Stopped
\<75% participation
Nab-paclitaxel and Alpelisib for the Treatment of Anthracycline Refractory Triple Negative Breast Cancer With PIK3CA or PTEN Alterations
A Phase-2, Two-Cohort Trial of Neoadjuvant Nab-Paclitaxel and Alpelisib in Anthracycline Refractory Triple Negative Breast Cancer With PIK3CA or PTEN Alterations
2 other identifiers
interventional
6
1 country
1
Brief Summary
This phase II trial studies how well nab-paclitaxel and alpelisib works in treating patients with triple negative breast cancer with PIK3CA or PTEN alterations that does not respond to anthracycline chemotherapy (anthrocycline refractory). Drugs used in chemotherapy, such as nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Alpelisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving nab-paclitaxel and alpelisib before surgery may help shrink the tumor before surgery.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Feb 2020
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 31, 2019
CompletedFirst Posted
Study publicly available on registry
January 2, 2020
CompletedStudy Start
First participant enrolled
February 5, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 22, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
September 22, 2025
CompletedSeptember 30, 2025
September 1, 2025
5.6 years
December 31, 2019
September 24, 2025
Conditions
Outcome Measures
Primary Outcomes (2)
Rate of pathological complete response (pCR/RCB-0)
Will be assessed by the alpelisib in combination with nab-paclitaxel in the neoadjuvant setting will improve rates.
Up to 30 days
Rate of minimal residual disease (RCB-I)
Will be assessed by the alpelisib in combination with nab-paclitaxel in the neoadjuvant setting will improve rates.
Up to 30 days
Secondary Outcomes (3)
Radiographic response rate (partial response + complete clinical response)
Up to 30 days
Incidence of adverse events
Up to 30 days
Progression free survival
Up to 30 days
Study Arms (1)
Treatment (alpelisib, nab-paclitaxel)
EXPERIMENTALPatients receive alpelisib PO QD on days 1-21, and nab-paclitaxel IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients may then undergo surgery to remove the tumor.
Interventions
Given PO
Given IV
Eligibility Criteria
You may qualify if:
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
- Stage I-III breast cancer
- Confirmed invasive triple-negative breast cancer defined as estrogen receptor (ER) \< 10%; progesterone receptor (PR) \< 10% by immunohistochemistry (IHC) and HER2 negative by American Society of Clinical Oncology (ASCO)/(College of American Pathologists) CAP guidelines
- Activating mutations in PIK3CA (cohort-1), or loss of function alterations in PTEN by next generation sequencing (NGS) or IHC (cohort-2) (based on MD Anderson Cancer Center \[MDACC\] Dako 6H2.1 assay)
- Fasting plasma glucose (FPG) =\< 140 mg/dL (7.7 mmol/L) and glycosylated hemoglobin (HbA1c) \< 6.4 %
- For patients with pre-diabetes (FPG \>= 100 mg/dL and/or HbA1c \>= 5.7%) at screening, recommend lifestyle changes according to American Diabetes Association (ADA) guidelines. A consultation with a diabetologist is highly recommended
- Chemotherapy insensitive disease as defined by ARTEMIS parameters (=\< 70 % volumetric response after four cycles of anthracycline-based therapy)
- Residual primary tumor size of at least 1.0 cm by imaging (ultrasound or MRI) or evidence of lymph node involvement by imaging (ultrasound or MRI) after anthracycline-based neoadjuvant chemotherapy (NACT)
- Received at least one dose of an anthracycline-based NACT. Patients are eligible if therapy was discontinued due to disease progression or therapy intolerance
- Prior to participation on ARTEMIS trial (2014-0185) multigated acquisition scan (MUGA) or echocardiogram showing left ventricular ejection fraction (LVEF) \>= 50%
- Absolute neutrophil count (ANC) \>= 1.5 x 10\^9 /L
- Platelets \>= 100 x 10\^9 /L
- Hemoglobin (Hb) \> 9 g/dL
- Fasting serum amylase =\< 2 x upper limit of normal (ULN)
- Fasting serum lipase =\< ULN
- +11 more criteria
You may not qualify if:
- Pregnant or lactating women
- Patient has a known hypersensitivity to alpelisib or any of its excipients
- Patients with clinically manifest diabetes mellitus (DM) or documented steroid induced DM
- Presence of distant metastatic disease (loco-regional nodal involvement of the ipsilateral axillary, internal mammary and/or supraclavicular nodes is not considered distant metastatic disease
- Prior radiation therapy of the primary breast carcinoma or axillary lymph nodes
- Patient is concurrently using other anti-cancer therapy
- Patients with an established diagnosis of diabetes mellitus type II or uncontrolled type II based on fasting plasma glucose or HbA1c
- Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will not be able to complete the entire study
- Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of alpelisib
- Male patients whose sexual partner(s) are WCBP who are not willing to use adequate contraception, during the study and for 4 weeks after the end of treatment
- Patients with \> grade 1 peripheral neuropathy
- Patients being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A within the last 5 days prior to study entry
- Serious concurrent illness or clinically-relevant active infection, including, but not limited to the following:
- Known active hepatitis B or C
- Known human immunodeficiency virus (HIV) infection
- +21 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- M.D. Anderson Cancer Centerlead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Senthilkumar Damodaran
M.D. Anderson Cancer Center
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
December 31, 2019
First Posted
January 2, 2020
Study Start
February 5, 2020
Primary Completion
September 22, 2025
Study Completion
September 22, 2025
Last Updated
September 30, 2025
Record last verified: 2025-09