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Neratinib and Paclitaxel With or Without Pertuzumab and Trastuzumab Before Combination Chemotherapy in Treating Patients With Metastatic or Locally Advanced Breast Cancer

Primary Purpose

Breast Inflammatory Carcinoma, Locally Advanced Breast Carcinoma, Metastatic Breast Carcinoma

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Cyclophosphamide
Doxorubicin
Laboratory Biomarker Analysis
Neratinib
Paclitaxel
Pertuzumab
Trastuzumab
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Inflammatory Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • Any other previous antitumor therapies for the current cancer event; this exclusion does not apply to phase Ib part of cohort 1
  • 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
      • Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication
      • Conduction abnormality requiring a pacemaker
      • Valvular disease with documented compromise in cardiac function
      • Symptomatic pericarditis
    • History of cardiac disease:

      • Myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricular (LV) function
      • History of documented congestive heart failure (CHF)
      • Documented cardiomyopathy
  • If you are pregnant, you will not be enrolled on this study

Sites / Locations

  • M D Anderson Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Group A (Cohort 1 Phase Ib)

Group B (Cohort 1 Phase II)

Group C (Cohort 2)

Arm Description

Patients 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.

Patients 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.

Patients 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.

Outcomes

Primary Outcome Measures

Pathologic complete response (pCR) rate determined by pCR in breast and axillary lymph nodes (pCR breast & nodes) in HER2+ and HER2-/hormone receptor (HR)+ inflammatory breast cancer treated with neratinib-based treatment
Evaluated at the end of neoadjuvant chemotherapy. In cohort 1, HER2-positive patients, will use Simon's optimum two-stage design to monitor the pathologic complete response rate. In cohort 2, HER2-negative/HR-positive patients, will also use Simon's minimax two-stage design to monitor the pathologic response rate.
Maximum tolerated dose of neratinib, pertuzumab, trastuzumab and paclitaxel treatment defined as dose limiting toxicities of grade 3 or higher
Will use the Bayesian modified toxicity probability interval dose-escalation algorithm to determine the maximum tolerated dose of neratinib.

Secondary Outcome Measures

Progression-free survival rate of HER2+, and HER2-/HR+ inflammatory breast cancer subgroups
Incidence of adverse events of combination therapy
Monitored separately by cohort by the method of Thall and Sung.

Full Information

First Posted
March 30, 2017
Last Updated
June 1, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT03101748
Brief Title
Neratinib and Paclitaxel With or Without Pertuzumab and Trastuzumab Before Combination Chemotherapy in Treating Patients With Metastatic or Locally Advanced Breast Cancer
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 29, 2018 (Actual)
Primary Completion Date
January 1, 2026 (Anticipated)
Study Completion Date
January 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
Detailed Description
PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of neratinib in combination with paclitaxel, pertuzumab, and trastuzumab in HER2-positive (HER2+) metastatic or locally advanced (stage III) breast cancer within 2 cycles. (Cohort 1: Phase Ib) II. To determine the pathologic complete response (pCR) rate of neratinib in combination with paclitaxel, pertuzumab, and trastuzumab followed by doxorubicin and cyclophosphamide (AC) in HER2+ metastatic or locally advanced (stage III) inflammatory breast cancer (IBC) patients. (Cohort 1: Phase II) III. To determine the pCR rate of neratinib in combination with paclitaxel followed by AC in HER2-negative/hormone receptor (HR)-positive (HER2-/HR+) metastatic or locally advanced (stage III) IBC patients. (Cohort 2) SECONDARY OBJECTIVES: I. To estimate 2 years progression free survival (PFS) rate of HER2+ metastatic or locally advanced (stage III) IBC patients, and HER2-/HR+ IBC patients treated with neratinib plus anthracycline and taxane based chemotherapy. (Cohort I Phase II and Cohort II) II. To determine toxicity and safety of the combination therapy. EXPLORATORY OBJECTIVES: I. To determine the adaptive target and downstream changes in pan-HER family members induced by one-week window period of neratinib based on tissue and blood based biomarkers. II. To determine the correlation between positive/negative changes in EGFR, HER2 and HER4 and the occurrence of pCR. III. To determine the rate of HER2 mutation in HER2+ IBC and HER2-/HR+ IBC. IV. To determine the association between HER2 mutation and pCR achieved by study combination therapy. V. To determine the correlation between tumor tissue based pharmacodynamic marker changes in association with circulating tumor cells (CTC) and circulating tumor deoxyribonucleic acid (ctDNA). OUTLINE: This is a phase I, dose-escalation study of neratinib followed by a phase II study. Patients are assigned to 1 of 3 groups. GROUP A (COHORT 1 PHASE IB): Patients receive neratinib orally (PO) once daily (QD) on days 1-21, paclitaxel intravenously (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): Patients 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): Patients 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. After completion of study treatment, patients are followed up at 1 month.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Inflammatory Carcinoma, Locally Advanced Breast Carcinoma, Metastatic Breast Carcinoma, Stage III Breast Cancer AJCC v7, Stage IIIA Breast Cancer AJCC v7, Stage IIIB Breast Cancer AJCC v7, Stage IIIC Breast Cancer AJCC v7, Stage IV Breast Cancer AJCC v6 and v7

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
43 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group A (Cohort 1 Phase Ib)
Arm Type
Experimental
Arm Description
Patients 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.
Arm Title
Group B (Cohort 1 Phase II)
Arm Type
Experimental
Arm Description
Patients 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.
Arm Title
Group C (Cohort 2)
Arm Type
Experimental
Arm Description
Patients 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.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
(-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Other Intervention Name(s)
Adriablastin, Hydroxydaunomycin, Hydroxyl Daunorubicin, Hydroxyldaunorubicin
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Drug
Intervention Name(s)
Neratinib
Other Intervention Name(s)
(2E)-N-(4-((3-chloro-4-((pyridin-2-yl)methoxy)phenyl)amino)-3-cyano-7-ethoxyquinolin-6-yl)-4-(dimethylamino)but-2-enamide, HKI 272, HKI-272, PB 272, PB-272
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Other Intervention Name(s)
Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
Pertuzumab
Other Intervention Name(s)
2C4, 2C4 Antibody, MoAb 2C4, Monoclonal Antibody 2C4, Omnitarg, Perjeta, rhuMAb2C4, RO4368451
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
Trastuzumab
Other Intervention Name(s)
ABP 980, ALT02, Anti-c-ERB-2, Anti-c-erbB2 Monoclonal Antibody, Anti-ERB-2, Anti-erbB-2, Anti-erbB2 Monoclonal Antibody, Anti-HER2/c-erbB2 Monoclonal Antibody, Anti-p185-HER2, c-erb-2 Monoclonal Antibody, HER2 Monoclonal Antibody, Herceptin, Herceptin Biosimilar PF-05280014, Herceptin Trastuzumab Biosimilar PF-05280014, Herzuma, Kanjinti, MoAb HER2, Monoclonal Antibody c-erb-2, Monoclonal Antibody HER2, Ogivri, Ontruzant, PF-05280014, rhuMAb HER2, RO0452317, SB3, Trastuzumab Biosimilar ABP 980, Trastuzumab Biosimilar ALT02, trastuzumab biosimilar EG12014, Trastuzumab Biosimilar HLX02, Trastuzumab Biosimilar PF-05280014, Trastuzumab Biosimilar SB3, Trastuzumab Biosimilar SIBP-01, Trastuzumab-anns, Trastuzumab-dkst, Trastuzumab-dttb, Trastuzumab-pkrb, Trastuzumab-qyyp, Trazimera
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Pathologic complete response (pCR) rate determined by pCR in breast and axillary lymph nodes (pCR breast & nodes) in HER2+ and HER2-/hormone receptor (HR)+ inflammatory breast cancer treated with neratinib-based treatment
Description
Evaluated at the end of neoadjuvant chemotherapy. In cohort 1, HER2-positive patients, will use Simon's optimum two-stage design to monitor the pathologic complete response rate. In cohort 2, HER2-negative/HR-positive patients, will also use Simon's minimax two-stage design to monitor the pathologic response rate.
Time Frame
Up to 84 days (course 4)
Title
Maximum tolerated dose of neratinib, pertuzumab, trastuzumab and paclitaxel treatment defined as dose limiting toxicities of grade 3 or higher
Description
Will use the Bayesian modified toxicity probability interval dose-escalation algorithm to determine the maximum tolerated dose of neratinib.
Time Frame
Up to 42 days (course 2)
Secondary Outcome Measure Information:
Title
Progression-free survival rate of HER2+, and HER2-/HR+ inflammatory breast cancer subgroups
Time Frame
Up to 2 years
Title
Incidence of adverse events of combination therapy
Description
Monitored separately by cohort by the method of Thall and Sung.
Time Frame
Up to 42 days (course 2)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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 Any other previous antitumor therapies for the current cancer event; this exclusion does not apply to phase Ib part of cohort 1 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 Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication Conduction abnormality requiring a pacemaker Valvular disease with documented compromise in cardiac function Symptomatic pericarditis History of cardiac disease: Myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of left ventricular (LV) function History of documented congestive heart failure (CHF) Documented cardiomyopathy If you are pregnant, you will not be enrolled on this study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rachel Layman, MD
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.mdanderson.org
Description
M D Anderson Cancer Center

Learn more about this trial

Neratinib and Paclitaxel With or Without Pertuzumab and Trastuzumab Before Combination Chemotherapy in Treating Patients With Metastatic or Locally Advanced Breast Cancer

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