Neratinib and Paclitaxel With or Without Pertuzumab and Trastuzumab Before Combination Chemotherapy in Treating Patients With Metastatic or Locally Advanced Breast Cancer
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT03101748 |
|
Recruitment Status :
Active, not recruiting
First Posted : April 5, 2017
Last Update Posted : December 14, 2022
|
Sponsor:
M.D. Anderson Cancer Center
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| 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 | Drug: Cyclophosphamide Drug: Doxorubicin Other: Laboratory Biomarker Analysis Drug: Neratinib Drug: Paclitaxel Biological: Pertuzumab Biological: Trastuzumab | Phase 1 Phase 2 |
Show detailed description
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 43 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | January 29, 2018 |
| Estimated Primary Completion Date : | January 1, 2026 |
| Estimated Study Completion Date : | January 1, 2026 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Breast cancer
MedlinePlus related topics:
Breast Cancer
| Arm | Intervention/treatment |
|---|---|
|
Experimental: Group A (Cohort 1 Phase Ib)
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.
|
Other: Laboratory Biomarker Analysis
Correlative studies Drug: Neratinib Given PO
Other Names:
Drug: Paclitaxel Given IV
Other Names:
Biological: Pertuzumab Given IV
Other Names:
Biological: Trastuzumab Given IV
Other Names:
|
|
Experimental: 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.
|
Drug: Cyclophosphamide
Given IV
Other Names:
Drug: Doxorubicin Given IV
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Drug: Neratinib Given PO
Other Names:
Drug: Paclitaxel Given IV
Other Names:
Biological: Pertuzumab Given IV
Other Names:
Biological: Trastuzumab Given IV
Other Names:
|
|
Experimental: 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.
|
Drug: Cyclophosphamide
Given IV
Other Names:
Drug: Doxorubicin Given IV
Other Names:
Other: Laboratory Biomarker Analysis Correlative studies Drug: Neratinib Given PO
Other Names:
Drug: Paclitaxel Given IV
Other Names:
|
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 [ Time Frame: Up to 84 days (course 4) ]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 [ Time Frame: Up to 42 days (course 2) ]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 [ Time Frame: Up to 2 years ]
- Incidence of adverse events of combination therapy [ Time Frame: Up to 42 days (course 2) ]Monitored separately by cohort by the method of Thall and Sung.
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03101748
Locations
| United States, Texas | |
| M D Anderson Cancer Center | |
| Houston, Texas, United States, 77030 | |
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
| Principal Investigator: | Rachel Layman, MD | M.D. Anderson Cancer Center |
Additional Information:
| Responsible Party: | M.D. Anderson Cancer Center |
| ClinicalTrials.gov Identifier: | NCT03101748 |
| Other Study ID Numbers: |
2016-0537 NCI-2017-00813 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 2016-0537 ( Other Identifier: M D Anderson Cancer Center ) |
| First Posted: | April 5, 2017 Key Record Dates |
| Last Update Posted: | December 14, 2022 |
| Last Verified: | December 2022 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
|
Carcinoma Breast Neoplasms Inflammatory Breast Neoplasms Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Neoplasms by Site Breast Diseases Skin Diseases Paclitaxel Cyclophosphamide Doxorubicin Liposomal doxorubicin Trastuzumab Albumin-Bound Paclitaxel |
Daunorubicin Pertuzumab Trastuzumab biosimilar HLX02 Antineoplastic Agents, Immunological Antibodies Immunoglobulins Antibodies, Monoclonal Antineoplastic Agents, Phytogenic Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action Immunosuppressive Agents Immunologic Factors |