Study Stopped
\<75% accrued
Neratinib and Paclitaxel With or Without Pertuzumab and Trastuzumab Before Combination Chemotherapy in Treating Patients With Metastatic or Locally Advanced Breast Cancer
A Phase 1b Study of Neratinib, Pertuzumab, and Trastuzumab With Taxol (3HT) in Metastatic and Locally Advanced Breast Cancer, and Phase II Study of 3HT Followed by AC in HER2 + Primary IBC, and Neratinib With Taxol (NT) Followed by AC in HR+ /HER2- Primary IBC
2 other identifiers
interventional
34
1 country
1
Brief Summary
This phase I/II trial studies the side effect and best dose of neratinib and to see how well it works with paclitaxel and with or without pertuzumab and trastuzumab before combination chemotherapy in treating patients with breast cancer that has spread to other places in the body (metastatic). Neratinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with pertuzumab and trastuzumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as paclitaxel, doxorubicin, and cyclophosphamide, 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. Giving neratinib, pertuzumab, trastuzumab, paclitaxel and combination chemotherapy may work better in treating patients with breast cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Feb 2018
Longer than P75 for phase_1
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
March 30, 2017
CompletedFirst Posted
Study publicly available on registry
April 5, 2017
CompletedStudy Start
First participant enrolled
February 19, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 13, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
May 13, 2025
CompletedResults Posted
Study results publicly available
February 12, 2026
CompletedFebruary 12, 2026
February 1, 2026
7.2 years
March 30, 2017
January 22, 2026
February 10, 2026
Conditions
Outcome Measures
Primary Outcomes (3)
Dose-Limiting Toxicities (DLTs) During Dose Escalation
Dose-limiting toxicities (DLTs) observed during the first two treatment cycles (approximately 6 weeks) among participants receiving escalating doses of neratinib in combination therapy in Cohort I Phase Ib. Participants With ≥1 DLT.
From treatment initiation through completion of 2 cycles (approximately 6 weeks)
Pathologic Complete Response (pCR) in HER2+ Metastatic or Locally Advanced IBC in Cohort I Phase II
Pathologic complete response (pCR) was defined as no residual invasive cancer in the breast and sampled lymph nodes at surgery (ypT0/Tis, ypN0). The primary analysis was conducted using the intent-to-treat (ITT) population; participants who did not undergo surgery were counted as non-pCR.
At surgery following completion of neoadjuvant therapy (approximately 18-24 weeks from treatment initiation).
Pathologic Complete Response (pCR) in HER2-Negative / HR-Positive IBC in Cohort II
Pathologic complete response (pCR) was defined as no residual invasive cancer in the breast and sampled lymph nodes at surgery (ypT0/Tis, ypN0). The primary analysis was conducted using the intent-to-treat (ITT) population; participants who did not undergo surgery were counted as non-pCR.
At the time of surgery (mastectomy), following completion of neoadjuvant therapy; approximately 18-24 weeks from treatment initiation.
Secondary Outcomes (1)
Event-Free Survival (EFS) Rate at 2 Years
From treatment initiation to 2 years after start of therapy.
Study Arms (3)
Group A (Cohort 1 Phase Ib)
EXPERIMENTALPatients receive neratinib PO QD on days 1-21, paclitaxel IV over 1-3 hours on days 1, 8, and 15, pertuzumab IV over 1 hour on day 1, and trastuzumab IV over 1-2 hours on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients without progression or excessive toxicity with metastatic disease may receive up to 4 additional courses and with locally advanced disease may receive up to 2 additional courses.
Group B (Cohort 1 Phase II)
EXPERIMENTALPatients receive neratinib, paclitaxel, pertuzumab, and trastuzumab as in Group A. Patients then receive doxorubicin IV and cyclophosphamide IV over 90 minutes on day 1. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo standard of care surgery.
Group C (Cohort 2)
EXPERIMENTALPatients receive neratinib PO QD on days 1-21, paclitaxel IV over 1-3 hours on days 1, 8, and 15. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery/ Patients then receive doxorubicin and cyclophosphamide as in Group B. Patients then undergo standard of care surgery.
Interventions
Given IV
Given IV
Correlative studies
Given PO
Given IV
Given IV
Given IV
Eligibility Criteria
You may qualify if:
- Histological confirmation of breast cancer
- Able to provide written informed consent for the trial
- Performance status of =\< 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
- Able to swallow oral medication
- Left ventricular ejection fraction (LVEF) assessment by 2-dimensional (D) echocardiogram or multi-gated acquisition (MUGA) scan performed within 90 days prior to registration must be \>= 50%
- Absolute neutrophil count \>= 1,500 /uL
- Platelets \>= 100,000 /uL
- Hemoglobin \>= 9 g/dL
- Creatinine clearance \>= 50 ml/min
- Total bilirubin =\< 1.5 X upper limit of normal (ULN), for patients with congenital unconjugated hyperbilirubinemia (Crigler-Najjar syndrome type 1 and 2, Gilbert syndrome) that transient hyperbilirubinemia can occur due to physiological condition, as long as there is clear documentation of diagnosis, allowed to be enrolled if direct (conjugated) bilirubin is =\< 1.5 X ULN
- Alanine aminotransferase and aspartate aminotransferase =\< 2.5 X ULN except in patients with aspartate aminotransferase (AST)/alanine aminotransferase (ALT) elevation that is declared to be caused due to liver metastasis, they are allowed to be enrolled as long as \< 5 x ULN
- Subject of childbearing potential should be willing to use effective methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study and through at least 4 months after the last dose of study drug; subject of childbearing potential is defined as has not been surgically sterilized or free from menses for \> 1 year; effective methods of birth control include: 1) use of hormonal birth control methods: pills, shots/injections, implants (placed under the skin by a health care provider), or patches (placed on the skin); 2) intrauterine devices (IUDs); 3) using 2 barrier methods (each partner must use 1 barrier method) with a spermicide; males must use the male condom (latex or other synthetic material) with spermicide; females must choose either a diaphragm with spermicide, or cervical cap with spermicide, or a sponge (spermicide is already in the contraceptive sponge); female patients of childbearing potential must have a negative urine pregnancy test no more than 7 days prior to starting study drug; 4) for male participant, they must agree and commit to use a barrier method of contraception while on treatment and for 3 months after the last dose of investigational product
- Cohort 1: Phase 1b: patient must have HER2 + (regardless of hormonal receptor status) metastatic or locally advanced breast cancer (IBC or Non-IBC); HER2 positive status is defined as strongly positive (3+) staining score by immunohistochemistry (IHC), or gene amplification using fluorescence in situ hybridization (FISH), if performed; if IHC is equivocal (2+), please refer to current American Society of Clinical Oncology (ASCO) guidelines algorithm for evaluation of HER2; HER2 negative status, which is determined by assays using IHC require negative (0 or 1+) staining score; if IHC is equivocal (2+) staining score, please refer to current ASCO guidelines algorithm for evaluation of HER2; IBC is determined by using international consensus criteria: onset: rapid onset of breast erythema, edema and/or peau d'orange, and/or warm breast, with/without an underlying breast mass; duration: history of such findings no more than 6 months; extent erythema occupying at least 1/3 of whole breast; pathology: pathologic confirmation of invasive carcinoma
- Cohort 1: Phase II: patient must have HER2+ (regardless of hormonal receptor status) stage III IBC or Stage IV IBC if the metastatic sites are amenable for local therapy (i.e. radiation and/ or surgery) and will have breast surgery
- Cohort 2: Patient must have HER2-/HR+ stage III IBC or Stage IV IBC if the metastatic sites are amenable for local therapy (i.e. radiation and/ or surgery) and will have breast surgery
You may not qualify if:
- Excisional biopsy or lumpectomy for the current breast cancer
- Any other previous malignancies (except for cervical in situ cancers treated only by local excision, and basal and squamous cell carcinomas of the skin) within 5 years
- Breast-feeding at screening or planning to become pregnant during the course of therapy
- History of active or known autoimmune disease that can cause diarrhea like (but not limited to) Addison's disease, celiac disease/gluten intolerance/irritable bowel syndrome, scleroderma
- Active infection or chronic infection requiring chronic suppressive antibiotics
- Known hepatitis B or hepatitis C with abnormal liver function tests
- Malabsorption syndrome, ulcerative colitis, inflammatory bowel disease, resection of the stomach or small bowel, or other disease or condition significantly affecting gastrointestinal function
- Persistent \>= grade 2 diarrhea regardless of etiology
- Sensory or motor neuropathy \>= grade 2
- Conditions that would prohibit intermittent administration of corticosteroids for paclitaxel premedication; however, corticosteroid can be dropped after confirming of no asthma like reaction to paclitaxel after 3 doses
- Uncontrolled hypertension defined as a systolic blood pressure (BP) \> 150 mmHg or diastolic BP \> 90 mmHg, with or without anti-hypertensive medications
- Cardiac disease (history of and/or active disease) that would preclude the use of any of the drugs included in the treatment regimen; this includes but is not confined to:
- Active cardiac diseases including:
- Symptomatic angina pectoris within the past 180 days that required the initiation of or increase in anti-anginal medication or other intervention
- Ventricular arrhythmias except for benign premature ventricular contractions
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- National Cancer Institute (NCI)collaborator
- M.D. Anderson Cancer Centerlead
Study Sites (1)
M D Anderson Cancer Center
Houston, Texas, 77030, United States
Related Publications (1)
Lim B, Marx A, Kai M, Alexander A, Bassett R Jr, Ma W, Willey J, Sun H, Nasrazadani A, Mohammad MM, Zhang J, Lucci A, Sun SX, Stauder MC, Whitman GJ, Le-Petross H, Valero V; MDACC Inflammatory Breast Cancer Team; Woodward WA, Layman RM. A phase Ib/II trial of neoadjuvant neratinib added to standard therapy in patients with HER2-positive or HR-positive/HER2-negative inflammatory breast cancer (including stage III and IV disease). Ther Adv Med Oncol. 2025 Oct 14;17:17588359251379392. doi: 10.1177/17588359251379392. eCollection 2025.
PMID: 41116969DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Rachel Layman, MD
- Organization
- The University of Texas MD Anderson Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Rachel Layman, MD
M.D. Anderson Cancer Center
Publication Agreements
- PI is Sponsor Employee
- Yes
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
March 30, 2017
First Posted
April 5, 2017
Study Start
February 19, 2018
Primary Completion
May 13, 2025
Study Completion
May 13, 2025
Last Updated
February 12, 2026
Results First Posted
February 12, 2026
Record last verified: 2026-02