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

NCT03289039 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 17-318
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 6

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

Conditions

Breast Cancer

Keywords

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival

  Progression-Free Survival (PFS) is defined as the time from randomization (or registration) to the earlier of progression or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Disease assessment were conducted at baseline and every two cycles after the first cycle.

  Participants were followed for PFS up to 20.3 months from registration.

Secondary Outcomes (3)

• Overall Survival

  Participants were followed for up to 38.4 months (3 years and 2 months) from registration to removal from protocol therapy or death.

• Overall Response Rate

  2 years

• Duration Of Responses

  2 years

Study Arms (2)

Neratinib

EXPERIMENTAL

* Neratinib will be administered orally once daily * Neratinib is dosed at 240mg (six 40mg tablets)

Drug: Neratinib

Neratinib + Fulvestrant

EXPERIMENTAL

* 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; Drug: Fulvestrant

Interventions

Neratinib DRUG

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)

Also known as: Nerlynx

Neratinib; Neratinib + Fulvestrant

Fulvestrant DRUG

Fulvestrant, works in treating breast cancer that has spread to other parts of the body

Also known as: Faslodex

Neratinib + Fulvestrant

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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. If ER quantification is not available, a determination of ER+ by IHC will suffice. 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) 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

You may not qualify if:

• 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 colestipol.
• Participants who have received previous therapy with neratinib.
• 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 known brain metastases that are untreated, symptomatic, or require therapy to control symptoms. Participants with a history of treated central nervous system (CNS) metastases are eligible. Treated brain metastases are defined as those without ongoing requirement for corticosteroids, as ascertained by clinical examination and/or brain imaging (magnetic resonance imaging or CT scan) completed during screening. Any corticosteroid use for brain metastases must have been discontinued without the subsequent appearance of symptoms for ≥ 7 days prior to registration. Treatment for brain metastases may include whole brain radiotherapy, radiosurgery, surgery or a combination as deemed appropriate by the treating physician. Radiation therapy must be completed at least 14 days prior to registration.
• 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.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Puma Biotechnology, Inc.: collaborator

Study Sites (6)

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Eastern Maine Medical Center

Brewer, Maine, 04412, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Dana-Farber/New Hampshire Oncology-Hematology

Londonderry, New Hampshire, 03053, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

UT Southwestern

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

neratinib; Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Jose Pablo Leone, MD
• Organization: Dana-Farber Cancer Institute

josep_leone@dfci.harvard.edu

617-632-3800

Study Officials

• Jose Leone, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 18, 2017
• First Posted: September 20, 2017
• Study Start: October 25, 2017
• Primary Completion: July 20, 2021
• Study Completion: July 20, 2021
• Last Updated: January 22, 2026
• Results First Posted: March 21, 2023

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)