Clinical Trials /

Anti-HER2 Therapy + Fulvestrant/Capecitabine in Women With HR+, HER2+, Non-visceral Metastases Stage IV Breast Cancer

NCT04337658

Description:

The purpose of this study is to evaluate the effectiveness of anti-HER2 therapy plus Fulvestrant or Capecitabine in women with hormone receptor positive (HR+), human epidermal growth factor receptor 2 positive (HER2+), non-visceral metastases, stage IV breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Anti-HER2 Therapy + Fulvestrant/Capecitabine in Women With HR+, HER2+, Non-visceral Metastases Stage IV Breast Cancer
  • Official Title: A Phase 3, Randomized, Multicenter, Open-Label Study to Compare the Efficacy and Safety of Anti-HER2 Therapy Plus Fulvestrant or Capecitabine in First-line Treatment of Women With HR+, HER2+, Non-visceral Metastases, Stage IV Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: FAVOR
  • NCT ID: NCT04337658

Conditions

  • HER2-positive Breast Cancer

Interventions

DrugSynonymsArms
PertuzumabPerjetaTrastuzumab± Pertuzumab+ Capecitabine
TrastuzumabHerceptinTrastuzumab± Pertuzumab+ Capecitabine
FulvestrantFaslodexTrastuzumab± Pertuzumab+ Fulvestrant
CapecitabineXelodaTrastuzumab± Pertuzumab+ Capecitabine

Purpose

The purpose of this study is to evaluate the effectiveness of anti-HER2 therapy plus Fulvestrant or Capecitabine in women with hormone receptor positive (HR+), human epidermal growth factor receptor 2 positive (HER2+), non-visceral metastases, stage IV breast cancer.

Detailed Description

      This is a prospective, randomized, 2-arm, multicenter study to compare the safety and
      efficiency of anti-HER2 therapy (Trastuzumab ± Pertuzumab) plus fulvestrant versus anti-HER2
      therapy (Trastuzumab ± Pertuzumab) plus capecitabine in women with hormone receptor positive
      (HR+), human epidermal growth factor receptor 2 positive (HER2+), non-visceral metastases,
      stage IV breast cancer. Subjects will be randomized into one of two treatment arms. Arm A
      subjects will receive the anti-HER2 therapy plus fulvestrant. Arm B subjects will receive the
      anti-HER2 therapy plus capecitabine. The use of Pertuzumab depends on patients' choices.
    

Trial Arms

NameTypeDescriptionInterventions
Trastuzumab± Pertuzumab+ FulvestrantExperimentalPertuzumab(Perjeta): Participants will receive 840 milligrams (mg) loading dose of pertuzumab, followed every 3 weeks thereafter by a dose of 420 mg via intravenous (IV) infusion until disease progression, unacceptable toxicity, withdrawal of consent, or study termination. It depends on the patient's choice. Trastuzumab(Herceptin): Participants will receive trastuzumab (8 mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles) administered by IV infusion every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent, or study termination. Fulvestrant(Faslodex): 500mg intramuscular injections at day 1, 15, 28 and every 4 weeks thereafter
  • Pertuzumab
  • Trastuzumab
  • Fulvestrant
Trastuzumab± Pertuzumab+ CapecitabineActive ComparatorPertuzumab(Perjeta): Participants will receive 840 milligrams (mg) loading dose of pertuzumab, followed every 3 weeks thereafter by a dose of 420 mg via intravenous (IV) infusion until disease progression, unacceptable toxicity, withdrawal of consent, or study termination. It depends on the patient's choice. Trastuzumab(Herceptin): Participants will receive trastuzumab (8 mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles) administered by IV infusion every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent, or study termination. Capecitabine: 1000mg/m2 orally Bid on day 1 to day 14 every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent, or study termination.
  • Pertuzumab
  • Trastuzumab
  • Capecitabine

Eligibility Criteria

        Inclusion Criteria:

          1. Patients provided written informed consent

          2. Postmenopausal or premenopausal or perimenopausal women aged 18-75 years:

               1. ≥60 years, or bilateral ovariectomy was previously performed, or

               2. <60 years, natural postmenopausal status (defined as a continuous period of at
                  least 12 months following spontaneous cessation without other pathological or
                  physiological causes), estrogen (E2) and follicle-stimulating hormone (FSH) are
                  present at postmenopausal levels

               3. Premenopausal or perimenopausal women, willing to receive luteinizing hormone
                  (LHRH) stimulation during the study

          3. Histologically or cytologically confirmed HR-positive (ER/PR≥10%), HER2-positive (IHC
             3+ or ISH+) breast cancer

          4. At least one measurable non-visceral metastatic lesion (liver, lung, pleura,
             pericardium, peritoneum, kidney, adrenal, brain or leptomeningeal metastases are
             excluded), HR-positive (ER/PR≥10%), HER2-positive (IHC 3+ or ISH+), (≥10 mm on
             T1-weighted, gadolinium-enhanced MRI) (RECIST v1.1)

          5. Previous treatment with HER2 inhibitors to be discontinued prior to first study
             treatment administration (at least 14 days for trastuzumab and other antibodies, at
             least 7 days for lapatinib)

          6. Previous chemotherapy, biological or target therapy to recurrent or metastatic disease
             are not allowed; Previous radiotherapy allowed, but radiotherapy must have been
             discontinued at least 14 days prior to first study treatment administration.

          7. Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 2

          8. Life expectancy > 24 weeks

          9. left ventricular ejection fraction (LVEF) of 50% or higher at baseline (within 42 days
             before randomization)

         10. Previous adjuvant chemotherapy treatment is allowed

         11. Previous adjuvant trastuzumab treatment is allowed

         12. Hormone therapy must have been discontinued at least 1 month prior to recruitment

         13. Patients with good compliance

         14. Patients must have recovered to baseline condition or to Common Terminology Criteria
             for Adverse Events (CTCAE) version 5.0 grade = 1 from any acute CTCAE v. 5.0 grade =2
             side effects of previous treatments

         15. Without infection of human immunodeficiency virus (HIV) on central laboratory assay
             results prior to randomization

         16. Alanine aminotransferase (ALT) </= 2.5 × the upper limit of normal (ULN), Aspartate
             aminotransferase (AST) </= 2.5 × ULN prior to randomization

         17. Total bilirubin (TBIL) </= 1.25 × ULN

         18. Alkaline phosphatase (ALK) </= 2.5 × ULN

         19. Gamma glutamyl transpeptidase (GGT) </= 2.5 × ULN

         20. Serum total bilirubin (TBil) </= 1.5 × ULN

         21. Serum creatinine (Scr) </= 1.5 × ULN

         22. WBC >/= 3×109/L, Blood neutrophil count >/= 1×109/L, Platelet count >/= 100×109/L, HB
             >/= 9 g/dL

         23. Albumin >/= 30g/L

         24. Women of child-bearing age who had a negative serum pregnancy test (within 14 days
             before randomization) should take effective contraceptive measures

        Exclusion Criteria:

          1. Primary and metastatic lesion lack of histological or cytological confirmation of
             HR-positive (ER/PR≥10%), HER2-positive (IHC 3+ or ISH+)

          2. Breast cancer with visceral metastases (liver, lung, pleura, pericardium, peritoneum,
             kidney, adrenal, brain or leptomeningeal metastases)

          3. Inflammatory breast cancer

          4. Having a life-threatening metastatic visceral disease, defined as extensive liver
             damage or brain or leptomeninges damage (past or present) or symptomatic pulmonary
             lymphatic diffusion. Patients with discrete pulmonary parenchyma metastasis were
             eligible if the investigators determined that their respiratory function was not
             significantly impaired by the disease.

          5. Disease progression or recurrence within 12 months after neo/adjuvant endocrine
             therapy

          6. Unable to tolerate endocrine therapy, including those who with symptoms, who have
             spread to the viscera, and who are at risk for short-term life-threatening
             complications (including uncontrolled thorax, pericardium, or abdominal cavity
             exudation, pulmonary lymphangitis, and more than 50% liver damage).

          7. CT or MRI confirmed the presence of brain or leptomeningeal metastases.

          8. Any other current malignancy or malignancy diagnosed within the past five years (other
             than breast cancer, carcinoma in situ of the cervix, skin basal cell carcinoma or
             squamous cell carcinoma), unless radical treatment is performed and there is no
             evidence of recurrence or metastasis within the last 5 years.

          9. Non- visceral metastatic lesions cannot be evaluated by RECIST v1.1

         10. Active infection with human immunodeficiency virus (HIV) prior to first study
             treatment administration.

         11. History of participating any other clinical trials within 30 days prior to
             randomization

         12. Known hypersensitivity (Grade 3 or 4) to Pertuzumab, Trastuzumab, Fulvestrant or
             Capecitabine or the excipients of any of the trial drugs

         13. Pregnancy or lactation

         14. Uncontrolled illnesses including symptomatic congestive heart failure, unstable angina
             pectoris, cardiac arrhythmia requiring therapy, myocardial infarction within the past
             6 months, or active infection

         15. severe pulmonary and renal disease

         16. Patients with GI tract disease resulting in an inability to take oral medication,
             malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures
             affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative
             colitis)

         17. Legal incompetence or limitation.

         18. Considered unable to complete the study or sign the informed consent due to a medical
             or mental disorder by the investigator.
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:up to approximately 2 years
Safety Issue:
Description:Progression-free survival (PFS) was defined as the time from randomization to first occurrence of progressive disease (PD), as determined by the investigator using RECIST v1.1, or death from any cause, whichever occurred first.

Secondary Outcome Measures

Measure:Overall Survival (OS)
Time Frame:up to approximately 2 years
Safety Issue:
Description:Overall survival (OS) was defined as the time from randomization to death from any cause.
Measure:Clinical Benefit Rate (CBR)
Time Frame:up to approximately 2 years
Safety Issue:
Description:Clinical Benefit Rate (CBR) is estimated by dividing the number of patients with CR, PR, or SD (for patients with measurable disease) ≥ 24 weeks from randomization.
Measure:Duration of Clinical Benefit (DOCB)
Time Frame:up to approximately 2 years
Safety Issue:
Description:DOCB was defined as the time from randomization to first occurrence of progressive disease (PD), as determined by the investigator using RECIST v1.1, or death from any cause, whichever occurred first (only for patients of CB)
Measure:Safety:Type incidence and severity (as graded by NCI CTCAE v 5.0)
Time Frame:up to approximately 2 years
Safety Issue:
Description:Seriousness and attribution to the study medications of AEs

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Second Affiliated Hospital, School of Medicine, Zhejiang University

Trial Keywords

  • breast cancer
  • hormone receptor positive
  • human epidermal growth factor receptor 2 positive
  • non-visceral metastases
  • fulvestrant
  • capecitabine
  • trastuzumab
  • pertuzumab

Last Updated

April 5, 2020