Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Capecitabine 7/7 Schedule With Neratinib in Patients With Metastatic HER2-Positive 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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03377387
Recruitment Status : Recruiting
First Posted : December 19, 2017
Last Update Posted : May 24, 2019
Sponsor:
Collaborator:
Puma Biotechnology, Inc.
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Brief Summary:
This is a phase l/II study. The purpose of this study is to test the safety of the study drug neratinib in combination with a standard chemotherapy drug called capecitabine at different doses to find out what effects, if any, it has on people. Capecitabine (Xeloda®) is approved by the Food and Drug Administration (FDA) for advanced breast cancer treatment. Neratinib is an investigational drug, meaning the FDA has not approved the use of this drug for advanced breast cancer. The combination of capecitabine and neratinib has been studied before in another study where capecitabine was administered using the standard dosing schedule. In this study, the investigators want to find out if a different dosing schedule of capecitabine combined with neratinib is safer. This different dosing schedule is experimental, meaning the administration schedule of capecitabine and neratinib is not FDA approved for treatment for HER2 positive advanced breast cancer.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Capecitabine Drug: Neratinib Behavioral: EORTC QLQ - BR23, EQ-5D-5L, EORTC QLQ-C30 Phase 1 Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Intervention Model: Single Group Assignment
Intervention Model Description: This is a phase Ib/II study of capecitabine 7/7 with neratinib in patients with HER2-positive metastatic breast cancer.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase Ib/II Study of Capecitabine 7/7 Schedule With Neratinib in Patients With Metastatic HER2-Positive Breast Cancer
Actual Study Start Date : December 13, 2017
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: capecitabine 7/7 with neratinib

In the phase I portion of the study, a 3+3 design will be used. Once the MTD is reached, the phase II portion will enroll up to 24 patients. Capecitabine will be taken orally in AM and PM (at the assigned dose per cohort) 7 days on and 7 days off. Neratinib is given as 240 mg daily continuously without stopping. A cycle is 28 days. Patients will be seen on Day 1 of each cycle (+/- 3 days).

The MD has been determined as 240mg of neratinib and 1000mg BID of capecitabine.

Drug: Capecitabine
Capecitabine will be taken orally in AM and PM (at the assigned dose per cohort) 7 days on and 7 days off. Phase II MD 1000mg BID of capecitabine.

Drug: Neratinib
Neratinib is given as 240 mg daily continuously without stopping. A cycle is 28 days. Phase II The MD has been determined as 240mg of neratinib

Behavioral: EORTC QLQ - BR23, EQ-5D-5L, EORTC QLQ-C30
Questionnaires Every Cycle (+/- 3 days) (For phase II)




Primary Outcome Measures :
  1. Maximum Tolerated Dose (MTD) [ Time Frame: 1 year ]
    If 0 of the 3 patients entered at a dose level experiences a DLT, another 3 patients will be treated at the next higher dose level. If 1 of 3 patients in a cohort experiences a DLT, then up to 3 additional patients will be treated at the same dose level. If none of these 3 additional patients experience a DLT, then the dose will be escalated to the next higher dose level. If > 2 of the initial 3 or 6 patients at a dose level experience a DLT, then the MTD will have been exceeded, and de-escalation is warranted. De-escalation will continue if > 2 of the initial 3 or 6 patients in a dose level cohort experience a DLT. There will be 2 dose de-escalation levels (dose levels -1 and -2) and one dose escalation (dose level +1) as shown in the table below. If < 1 of 6 patients, at that dose level, experience a DLT, then that dose level will be confirmed as the MTD.



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.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Breast Cancer
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Aged ≥18 years at signing of informed consent.
  • Histologically confirmed MBC, current stage IV.
  • Documented HER2 overexpression (immunohistochemistry (IHC) 3+ or gene-amplified tumor with fluorescence in situ hybridization (FISH) ratio of ≥ 2.0.
  • For phase Ib, any line of prior treatments is permitted including prior neratinib and capecitabine.
  • For phase II, up to 4 prior chemotherapy-based treatments in the metastatic setting are allowed. Patients must have had prior trastuzumab-based therapy. Prior neratinib treatment is not permitted. Prior capecitabine is allowed, if not combined with neratinib.
  • Measurable or non-measurable disease is permitted as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) for phase 1b. For phase 2, patients must have measurable disease as defined in RECIST v1.1.
  • Left ventricular ejection fraction (LVEF) ≥50% measured by multiple-gated acquisition scan (MUGA) or echocardiogram (ECHO).
  • Eastern Cooperative Oncology Group (ECOG) status of 0 to 1
  • Hematologic parameters: white blood cell (WBC) count of > 3000/ul, absolute neutrophil count (ANC) ≥ 1000/ul, platelets ≥ 50,000/ul, hemoglobin ≥ 8.0 g/dl
  • Non-hematologic parameters: bilirubin ≤ 1.5 mg/dl, AST/ALT ≤ 3.0 x upper limit of normal (ULN) (≤ 5.0 x ULN if liver metastases are involved)
  • Creatinine ≤1.5 mg/dl Patients with "treated and stable" brain lesions of a duration of ≥ 2 months may be enrolled.
  • Negative β-human chorionic gonadotropin (hCG) pregnancy test for premenopausal women of reproductive capacity (those who are biologically capable of having children) and for women less than 12 months after menopause.
  • Women of childbearing potential must agree and commit to the use of a highly effective method of contraception as determined to be acceptable by the investigator, from the time of informed consent until 28 days after the last dose of the investigational product. Men must agree and commit to use a barrier method of contraception while on treatment and for 3 months after last dose of investigational products.
  • Provide written, informed consent to participate in the study and follow the study procedures

Exclusion Criteria:

  • Active uncontrolled cardiac disease, including cardiomyopathy, congestive heart failure (New York Heart Association functional classification of ≥2), unstable angina, myocardial infarction within 12 months of enrollment, or ventricular arrhythmia
  • Received prior therapy resulting in a cumulative epirubicin dose >900 mg/m2 or cumulative doxorubicin dose >450 mg/m2. If another anthracycline or more than one anthracycline has been used, the cumulative dose must not exceed the equivalent of 450 mg/m^2 doxorubicin.
  • Any major surgery ≤28 days prior to the initiation of investigational products, or received anti-cancer therapy (including chemotherapy, biological therapy, hormonal therapy, investigational agents, or other anti-cancer therapy) administered ≤14 days prior to the initiation of investigational products.
  • Received radiation therapy ≤14 days prior to initiation of investigational products.
  • QTc interval >450 ms for men or 470 ms for women, or known history of QTc prolongation or Torsades de Pointes.
  • Active hepatitis B or C
  • Active infection or unexplained fever >38.5°C (>101.3°F) within 2 weeks prior to enrollment.
  • Significant chronic gastrointestinal disorder with diarrhea as a major symptom (e.g., Crohn's disease, malabsorption, or Grade ≥2 diarrhea of any etiology screening).
  • Known dihydropyrimidine dehydrogenase deficiency.
  • Known hypersensitivity to 5-fluorouracil or to any component of the investigational products or compounds of similar chemical composition.
  • Pregnant patients or currently breast-feeding.

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): NCT03377387


Contacts
Layout table for location contacts
Contact: Chau Dang, MD 914-367-7181 dangc@mskcc.org
Contact: Shanu Modi, MD 646-888-4564

Locations
Layout table for location information
United States, Connecticut
Hartford Healthcare Cancer Institute @ Hartford Hospital Recruiting
Hartford, Connecticut, United States, 06102
Contact: Rajani Nadkarni, MD    203-238-7747      
United States, Florida
Baptist Health South Florida Recruiting
Miami, Florida, United States, 33143
Contact: Grace Wang, MD    305-595-2141      
United States, New Jersey
Memorial Sloan Kettering at Basking Ridge Recruiting
Basking Ridge, New Jersey, United States, 07920
Contact: Chau Dang, MD    914-367-7181      
Memorial Sloan Kettering Monmouth Recruiting
Middletown, New Jersey, United States, 07748
Contact: Chau Dang, MD    914-367-7181      
Memorial Sloan Kettering Bergen Recruiting
Montvale, New Jersey, United States, 07645
Contact: Chau Dang, MD    914-367-7181      
United States, New York
Memorial Sloan Kettering Commack Recruiting
Commack, New York, United States, 11725
Contact: Chau Dang, MD    914-367-7181      
Memorial Sloan Kettering Westchester Recruiting
Harrison, New York, United States, 10604
Contact: Chau Dang, MD    914-367-7181      
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Chau Dang, MD    914-367-7181      
Contact: Shanu Modi, MD    646-888-4564      
Principal Investigator: Chau Dang, MD         
Memorial Sloan Kettering Nassau Recruiting
Uniondale, New York, United States, 11553
Contact: Chau Dang, MD    914-367-7181      
United States, Pennsylvania
Lehigh Valley Health Network Recruiting
Allentown, Pennsylvania, United States, 18103
Contact: Ranju Gupta, MD    610-402-7880      
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Puma Biotechnology, Inc.
Investigators
Layout table for investigator information
Principal Investigator: Chau Dang, MD Memorial Sloan Kettering Cancer Center

Additional Information:
Layout table for additonal information
Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT03377387     History of Changes
Other Study ID Numbers: 17-585
First Posted: December 19, 2017    Key Record Dates
Last Update Posted: May 24, 2019
Last Verified: May 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Memorial Sloan Kettering Cancer Center:
Capecitabine
Neratinib
HER2-Positive
17-585

Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Capecitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents