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Neratinib +/- Fulvestrant in HER2+, ER+ Metastatic Breast Cancer

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ClinicalTrials.gov Identifier: NCT03289039
Recruitment Status : Recruiting
First Posted : September 20, 2017
Last Update Posted : February 8, 2019
Sponsor:
Collaborator:
Puma Biotechnology, Inc.
Information provided by (Responsible Party):
Heather A. Parsons, Dana-Farber Cancer Institute

Brief Summary:

This research study is studying a drug called Neratinib with and without Fulvestrant as possible treatments for HER2-positive breast cancer .

The interventions involved in this study are:

  • Neratinib and Fulvestrant
  • Neratinib alone

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Neratinib Drug: Fulvestrant Phase 2

Detailed Description:

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied.

The FDA (the U.S. Food and Drug Administration) has approved Neratinib as a treatment for breast cancer. Fulvestrant has been FDA approved for treatment of metastatic hormone receptor positive breast cancer.

The purpose of this research study is to determine how well neratinib, by itself or together with Fulvestrant, works in treating breast cancer that has spread to other parts of the body. Neratinib is a recently discovered oral drug that may stop breast cancer cells from growing abnormally by inhibiting (or blocking) members of a family of proteins that include Human Epidermal Growth Factor Receptor 2 (HER2).

Neratinib has been used in other research studies and information from those other research studies suggests that neratinib may help to shrink or stabilize HER2-positive breast cancer in this research study.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 152 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Neratinib With or Without Fulvestrant in HER2-Positive, ER-Positive Metastatic Breast Cancer
Actual Study Start Date : October 25, 2017
Estimated Primary Completion Date : March 31, 2021
Estimated Study Completion Date : March 31, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Neratinib
  • Neratinib will be administered orally once daily
  • Neratinib is dosed at 240mg (six 40mg tablets)
Drug: Neratinib
Neratinib is a recently discovered oral drug that may stop breast cancer cells from growing abnormally by inhibiting (or blocking) members of a family of proteins that include Human Epidermal Growth Factor Receptor 2 (HER2)
Other Name: Nerlynx

Experimental: Neratinib + Fulvestrant
  • Neratinib will be administered orally once daily
  • Neratinib is dosed at 240mg (six 40mg tablets)
  • Fulvestrant will be administered intramuscular as an injection (shot) on day 1 and 15 of cycle 1, day 1 of cycle 2, and then on day 1 of each subsequent cycle.
  • Fulvestrant is dosed as 250 mg/5mL (x2) for a total of 500 mg via intramuscular injection (two injections).
Drug: Neratinib
Neratinib is a recently discovered oral drug that may stop breast cancer cells from growing abnormally by inhibiting (or blocking) members of a family of proteins that include Human Epidermal Growth Factor Receptor 2 (HER2)
Other Name: Nerlynx

Drug: Fulvestrant
Fulvestrant, works in treating breast cancer that has spread to other parts of the body
Other Name: Faslodex




Primary Outcome Measures :
  1. Progression Free Survival [ Time Frame: 5 years ]
    Estimate the efficacy, as measured by progression free survival (PFS), of neratinib combined with fulvestrant compared with neratinib alone in patients with inoperable locally advanced or metastatic HER2 positive, ER positive breast cancer


Secondary Outcome Measures :
  1. Overall Survival [ Time Frame: 5 years ]
    Estimate the efficacy, as measured by overall survival (OS) of neratinib combined with fulvestrant compared with neratinib alone in patients with inoperable locally advanced or metastatic HER2-positive, ER-positive breast cancer.

  2. Overall Response Rate [ Time Frame: 2 years ]
    Estimate the clinical activity, as measured by overall response rate (ORR) of neratinib combined with fulvestrant compared with neratinib alone in patients with inoperable locally advanced or metastatic HER2-positive, ER-positive breast cancer.

  3. Duration Of Response [ Time Frame: 2 years ]
    Estimate the clinical activity, as measured by duration of response, of neratinib combined with fulvestrant compared with neratinib alone in patients with inoperable locally advanced or metastatic HER2-positive, ER-positive breast cancer.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants must have histologically or cytologically confirmed inoperable locally advanced or metastatic ER+ breast cancer. To fulfill the requirement for ER+ disease, a breast cancer must express, by immunohistochemistry (IHC), ER in ≥10% of cells, on the most recent biopsy. Central confirmation of ER status is not required.
  • Participants must have documented HER2+ disease by overexpression and/or gene amplification on the most recent biopsy, per current ASCO-CAP (American Society of Clinical Oncology - College of American Pathologists) 2013 guidelines. Central confirmation of HER2 status is not required.
  • Participants must have received prior therapy with the following agents in any combination, and in setting (i.e., neoadjuvant, adjuvant, metastatic, etc.). These therapies do not need to be the most recent line of therapy.

    • Trastuzumab
    • Pertuzumab
    • Ado-trastuzumab emtansine (T-DM1)
  • Participants must agree to undergo a research biopsy of a reasonably accessible metastatic lesion (chest wall, skin, subcutaneous tissue, lymph nodes, skin, breast, bones, lung, and liver metastases). If a reasonably accessible metastatic lesion is not available, the patient may go on study provided that archived tissue is available. However, if a reasonably accessible site is available for biopsy, the patient must agree to biopsy. Any patients not undergoing biopsy must be approved for study enrollment by the Overall Principal Investigator at DFCI. Biopsies may be done with local anesthesia or intravenous conscious sedation, according to institutional guidelines. If a biopsy requires general anesthesia, then it is only allowed if acquisition of tissue is clinically indicated, and excess tissue may be collected for research purposes. Patients without sites available for biopsy must have available tissue [archived formalin-fixed paraffin embedded blocks (FFPB), blocks from which slides can be created, or fresh frozen tissue from original diagnosis or metastatic setting] for correlative studies. Tissue needs to be located and available at the time of registration See Section 9.3 for more details.
  • Women ≥ 18 years of age. Men are not eligible.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (see Appendix A).
  • Participants must have normal organ and marrow function as described below:

    • Absolute neutrophil count ≥1,000/uL
    • Platelets ≥75,000/uL
    • Hemoglobin ≥8g/dL
    • Total bilirubin ≤ 1.5 X institutional upper limit of normal (ULN); in case of known Gilbert's syndrome, <2 x ULN is allowed
    • AST(SGOT)/ALT(SGPT) ≤3X institutional ULN without liver metastases, or ≤5X institutional ULN with liver metastases
    • Creatinine clearance ≥ 50 mL/min
    • Left ventricular ejection fraction ≥50%, as determined by RVG (MUGA) or echocardiogram (ECHO) within 60 days prior to initiation of protocol therapy
  • Participants may have received any number of prior therapies as long as they have adequate performance status and meet all other eligibility criteria.
  • Women of childbearing potential (including premenopausal women and women less than 12 months after menopause) must have a negative β-human chorionic gonadotropin (hCG) urine pregnancy test within 4 weeks of registration.
  • The effects of neratinib and fulvestrant on the developing human fetus are unknown. For this reason and because SERD agents are known to be teratogenic, women of child-bearing potential must agree to be abstinent, or to use a highly effective double barrier method of contraception (e.g, a combination of male condom with an intravaginal device such as the cervical cap, diaphragm, or vaginal sponge with spermicide) or a non-hormonal method, while enrolled in the study, until at least 28 days after the last dose of neratinib or 1 year after the last dose of fulvestrant. Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately. If a woman is of childbearing potential, she must agree to use adequate contraception prior to the study, for the duration of study participation, and for one year after completion of the study drug.
  • Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

  • Participants who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to neratinib or fulvestrant.
  • Participants who have known hypersensitivity to any component of loperamide or budesonide.
  • Participants who have received previous therapy with neratinib or fulvestrant.
  • Participants who have received anti-cancer therapy (including chemotherapy, biological therapy, investigational agents, hormonal therapy, or other anti-cancer therapy) or radiotherapy within ≤14 days prior to the planned initiation of investigational products, or those who have not recovered to grade ≤1from adverse events due to their most recent therapy (excepting alopecia).
  • Participants who have had any major surgery ≤28 days prior to the planned initiation of study therapy, or those who have not recovered from adverse events due to agents/surgery administered more than 4 weeks earlier.
  • Participants who are receiving any other investigational agents.
  • Participants with symptomatic or progressive brain metastases, or requiring steroids to control symptoms of brain metastases.
  • Participant has 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.
  • Participant has a QTc interval >470 ms or known history of QTc prolongation or Torsade de Pointes.
  • Participant has an active infection or unexplained fever >38.5°C (101.3°F).
  • Participant has had another malignancy within the past 5 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the breast, cervix or vulva; or c) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder, or benign tumors of the adrenal or pancreas.
  • Participant has significant chronic gastrointestinal disorder with diarrhea as a major symptom (e.g., Crohn's disease, malabsorption, or Grade ≥2 (NCI CTCAE v.4.0) diarrhea of any etiology at screening).
  • Participant has known active infection with hepatitis B or hepatitis C virus. Hepatitis B and C serology testing is not required, unless active infection is suspected.
  • Participant is unable or unwilling to swallow tablets.
  • Participant has evidence of significant medical illness, abnormal laboratory finding, or psychiatric illness/social situations that would, in the Investigator's judgment, limit compliance with study requirements.
  • Pregnant women are excluded from this study because fulvestrant is a SERD agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with neratinib and/or fulvestrant, breastfeeding should be discontinued if the mother is treated with neratinib and/or fulvestrant.

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): NCT03289039


Contacts
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Contact: Heather A. Parsons, MD 617-632-3800 HeatherA_Parsons@dfci.harvard.edu
Contact: Paulina Lange 617-632-2257 PaulinaB_Lange@dfci.harvard.edu

Locations
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United States, Indiana
Indiana University Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Tarah Ballinger, MD       Tarahb@iu.edu   
Principal Investigator: Tarah Ballinger, MD         
United States, Maine
Eastern Maine Medical Center Recruiting
Brewer, Maine, United States, 04412
Contact: Sarah Sinclair, MD       ssinclair@emhs.org   
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Heather A. Parsons, MD       HeatherA_Parsons@dfci.harvard.edu   
Principal Investigator: Heather A. Parson, MD         
Berkshire Medical Center Recruiting
Pittsfield, Massachusetts, United States, 01201
Contact: Michael DeLeo, MD       mdeleo@bhs1.org   
United States, New Hampshire
Dana-Farber/New Hampshire Oncology-Hematology Recruiting
Londonderry, New Hampshire, United States, 03053
Contact: Fred Briccetti, MD       fred_briccetti@dfci.harvard.edu   
Principal Investigator: Fred Briccetti, MD         
United States, Ohio
The Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Contact: Robert Wesolowski, MD       Robert.Wesolowski@osumc.edu   
United States, Texas
UT Southwestern Recruiting
Dallas, Texas, United States, 75390
Contact: Barbara Haley, MD       barbara.haley@utsouthwestern.edu   
Sponsors and Collaborators
Dana-Farber Cancer Institute
Puma Biotechnology, Inc.
Investigators
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Principal Investigator: Heather A. Parsons, MD Dana-Farber Cancer Institute

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Responsible Party: Heather A. Parsons, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT03289039     History of Changes
Other Study ID Numbers: 17-318
First Posted: September 20, 2017    Key Record Dates
Last Update Posted: February 8, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Heather A. Parsons, Dana-Farber Cancer Institute:
Breast Cancer

Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Fulvestrant
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Estrogen Receptor Antagonists
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs