Clinical Trials /

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

NCT03289039

Description:

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

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Neratinib +/- Fulvestrant in HER2+, ER+ Metastatic Breast Cancer
  • Official Title: A Phase 2 Study of Neratinib With or Without Fulvestrant in HER2-Positive, ER-Positive Metastatic Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: 17-318
  • NCT ID: NCT03289039

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
NeratinibNerlynxNeratinib
FulvestrantFaslodexNeratinib + Fulvestrant

Purpose

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

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.
    

Trial Arms

NameTypeDescriptionInterventions
NeratinibExperimentalNeratinib will be administered orally once daily Neratinib is dosed at 240mg (six 40mg tablets)
  • Neratinib
Neratinib + FulvestrantExperimentalNeratinib 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).
  • Neratinib
  • Fulvestrant

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival
Time Frame:5 years
Safety Issue:
Description: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

Measure:Overall Survival
Time Frame:5 years
Safety Issue:
Description: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.
Measure:Overall Response Rate
Time Frame:2 years
Safety Issue:
Description: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.
Measure:Duration Of Response
Time Frame:2 years
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Breast Cancer

Last Updated

November 7, 2017