Clinical Trials /

The Efficacy of Fulvestrant in ESR1(Estrogen Receptor 1) Mutated Metastatic Breast Cancer

NCT03202862

Description:

This is an open-label, single arm, phase II trial to evaluate the efficacy and safety of 500mg Fulvestrant (Faslodex®) in ESR1 mutated postmenopausal women with hormone receptor positive, HER2 negative locally advanced or metastatic breast cancer after previous aromatase inhibitor therapy. Fifty patients will be enrolled and treated with 500 mg Fulvestrant until disease progression or study closed. Treatment will continue until disease progression, unless any of the criteria for treatment discontinuation are met first. If a patient progresses during the treatment period, the patient must be withdrawn from the treatment and further treatment will be at the investigator's discretion.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: The Efficacy of Fulvestrant in ESR1(Estrogen Receptor 1) Mutated Metastatic Breast Cancer
  • Official Title: An Open-Label, Single Arm, Phase II Trial to Evaluate the Efficacy of 500mg Fulvestrant (Faslodex) in ESR1 Mutated Postmenopausal Women With Hormone Receptor Positive, HER2 Negative Locally Advanced or Metastatic Breast Cancer After Previous Aromatase Inhibitor Treatment

Clinical Trial IDs

  • ORG STUDY ID: Fulvestrant in ESR1 Mutated BC
  • NCT ID: NCT03202862

Conditions

  • Breast Neoplasms

Interventions

DrugSynonymsArms
FulvestrantESR1 mutated

Purpose

This is an open-label, single arm, phase II trial to evaluate the efficacy and safety of 500mg Fulvestrant (Faslodex®) in ESR1 mutated postmenopausal women with hormone receptor positive, HER2 negative locally advanced or metastatic breast cancer after previous aromatase inhibitor therapy. Fifty patients will be enrolled and treated with 500 mg Fulvestrant until disease progression or study closed. Treatment will continue until disease progression, unless any of the criteria for treatment discontinuation are met first. If a patient progresses during the treatment period, the patient must be withdrawn from the treatment and further treatment will be at the investigator's discretion.

Detailed Description

      All patients will be followed up for disease progression, regardless of whether they have
      discontinued treatment, unless they have withdrawn consent.

      Efficacy will be determined based on tumor assessments performed by each investigator
      according to RECIST 1.1. Safety will be monitored based on the frequency and severity of
      adverse events (AEs), as assessed by Common Terminology Criteria (CTC) grade version 4.0.

      Tumor assessments will be assessed by computed tomography (CT) or magnetic resonance imaging
      (MRI) or X ray if necessary every 12 weeks for all patients until documented evidence of
      objective disease progression.

      Reporting of SAEs to regulatory authorities will be done by the investigator in accordance
      with CFDA regulations.
    

Trial Arms

NameTypeDescriptionInterventions
ESR1 mutatedExperimentalESR1 mutated postmenopausal women with hormone receptor positive, HER2 negative locally advanced or metastatic breast cancer after previous aromatase inhibitor therapy
  • Fulvestrant

Eligibility Criteria

        Inclusion Criteria:

          1. Signed informed consent document on file.

          2. Postmenopausal woman, defined as a woman fulfilling any of the following criteria:

               -  Having undergone a bilateral oophorectomy;

               -  Age ≥60 years;

               -  Age <60 years and amenorrheic for 12 or more months in the absence of
                  chemotherapy, tamoxifen, toremifene, or ovarian suppression and FSH (follicle
                  stimulating hormone) and oestradiol level in the postmenopausal range (utilizing
                  ranges from the local laboratory facility);

               -  If taking tamoxifen or toremifene, and age < 60 years, then FSH and plasma
                  oestradiol level in the postmenopausal ranges (utilizing ranges from the local
                  laboratory facility).

          3. Histological/cytological confirmation of advanced breast cancer or inoperable locally
             advanced disease and documented positive oestrogen receptor status, ER (Estrogen
             Receptor) positive and/or PgR (Progesterone Receptor) positive of primary or
             metastatic tumour tissue, according to the local laboratory parameters.

          4. Relapsed or progressed during prior treatment with aromatase inhibitor, meeting either
             of the following criteria:

               -  Relapsing during, or after of completion of adjuvant aromatase inhibitors
                  therapy, i.e. anastrozole, letrozole, exemestane. Duration of adjuvant aromatase
                  inhibitors treatment should be at least 2 years.

               -  Progressing on at least 6 months first line aromatase inhibitors therapy for
                  advanced disease

          5. Metastatic disease must be measurable or evaluable. Patients fulfilling one of the
             following criteria:

               -  Patients with measurable disease as per RECIST 1.1 criteria.

               -  Patients with bone lesions, lytic or mixed (lytic + sclerotic), which had not
                  been previously irradiated, in the absence of measurable disease as defined by
                  RECIST 1.1 criteria.

          6. The blood sample is clarified to be ESR1 mutated, The mutation should be: Y537C,
             Y537N, Y537S, S463P and D538G.

          7. ECOG performance status 0,1.

          8. Patients with life expectancy of more than 3 months.

        Exclusion Criteria:

          1. Presence of life-threatening metastatic visceral disease, defined as extensive hepatic
             involvement, or any degree of brain or leptomeningeal involvement (past or present),
             or symptomatic pulmonary lymphangitic spread. Patients with discrete pulmonary
             parenchymal metastases are eligible, provided their respiratory function is not
             compromised as a result of disease.

          2. Previous systemic chemotherapy for advanced breast cancer.

          3. Received endocrine therapy for advanced breast cancer > 1 lines;

          4. Extensive radiation therapy within the last 4 weeks (greater than or equal to 30%
             marrow or whole pelvis or spine) or cytotoxic treatment within the past 4 weeks prior
             to screening laboratory assessment, or strontium-90 (or other radiopharmaceuticals)
             within the past 3 months.

          5. Prior treatment with Fulvestrant.

          6. HER2 overexpression or gene amplification, ie, immunohistochemistry (IHC)3+ positive
             or fluorescence in situ hybridisation (FISH) positive, where appropriate

          7. Treatment with a non-approved or experimental drug within 4 weeks.

          8. Current or prior malignancy within previous 3 years (other than breast cancer or
             adequately treated basal cell or squamous cell carcinoma of the skin or in-situ
             carcinoma of the cervix)

          9. Any of the following laboratory values :

               -  Platelets < 100 10^9 / L

               -  Total bilirubin >1.5 ULRR

               -  ALT( Alanine transaminase) or AST(Aspartate transaminase)>2.5 ULRR if no
                  demonstrable liver metastases or > 5 ULRR in presence of liver metastases

               -  Severe renal impairment (creatinine clearance < 30ml/min)

         10. History of:

             •bleeding diathesis (i.e., disseminated intravascular coagulation [DIC], clotting
             factor deficiency), or long-term anticoagulant therapy (other than antiplatelet
             therapy and low dose warfarin).

         11. History of hypersensitivity to active or inactive excipients of Fulvestrant and castor
             oil.

        Any severe concomitant condition which makes it undesirable for the patient to participate
        in the trial or which would jeopardize compliance with the trial protocol. E.g.
        uncontrolled cardiac disease or uncontrolled diabetes mellitus.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:N/A
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Tumour assessment
Time Frame:An average of 5 years, up to 10 years.
Safety Issue:
Description:The study will be closed at all the patients progressed or 12 months after the last patient has been recruited depends on which one met first. From date of the first recruitment until the date of all the patients progressed or 12 months after the last patient has been recruited, whichever came first, assessed up to 10 years.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Fudan University

Trial Keywords

  • fulvestrant
  • ESR1

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