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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04337658
Recruitment Status : Not yet recruiting
First Posted : April 8, 2020
Last Update Posted : April 8, 2020
Sponsor:
Information provided by (Responsible Party):
xuexin he, Second Affiliated Hospital, School of Medicine, Zhejiang University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
HER2-positive Breast Cancer Drug: Pertuzumab Drug: Trastuzumab Drug: Fulvestrant Drug: Capecitabine Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 493 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Estimated Study Start Date : July 1, 2020
Estimated Primary Completion Date : April 30, 2024
Estimated Study Completion Date : April 30, 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Trastuzumab± Pertuzumab+ Fulvestrant

Pertuzumab(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

Drug: Pertuzumab
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.
Other Name: Perjeta

Drug: Trastuzumab
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.
Other Name: Herceptin

Drug: Fulvestrant
500mg intramuscular injections at day 1, 15, 28 and 4 weeks thereafter
Other Name: Faslodex

Active Comparator: Trastuzumab± Pertuzumab+ Capecitabine

Pertuzumab(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.

Drug: Pertuzumab
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.
Other Name: Perjeta

Drug: Trastuzumab
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.
Other Name: Herceptin

Drug: 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.
Other Name: Xeloda




Primary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: up to approximately 2 years ]
    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 :
  1. Overall Survival (OS) [ Time Frame: up to approximately 2 years ]
    Overall survival (OS) was defined as the time from randomization to death from any cause.

  2. Clinical Benefit Rate (CBR) [ Time Frame: up to approximately 2 years ]
    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.

  3. Duration of Clinical Benefit (DOCB) [ Time Frame: up to approximately 2 years ]
    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)

  4. Safety:Type incidence and severity (as graded by NCI CTCAE v 5.0) [ Time Frame: up to approximately 2 years ]
    Seriousness and attribution to the study medications of AEs



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.

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): NCT04337658


Contacts
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Contact: Xuexin He, MD +8618329139569 ext 057187784818 xuexinhe@zju.edu.cn

Locations
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China, Guangdong
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, China, 510000
Contact: Jiajia Huang, MD         
China, Zhejiang
Second Affiliated Hospital, Zhejiang University, School of Medicine
Hangzhou, Zhejiang, China, 310000
Contact: Xuexin He, MD    +8618329139569 ext 057187784818    xuexinhe@zju.edu.cn   
Sponsors and Collaborators
Second Affiliated Hospital, School of Medicine, Zhejiang University
Investigators
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Principal Investigator: Xuexin He, MD The Second Affiliated Hospital of Zhejiang University School of Medicine (SAHZU)
Principal Investigator: Jiajia Huang, MD Sun Yat-sen University

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Responsible Party: xuexin he, Principal Investigator, Second Affiliated Hospital, School of Medicine, Zhejiang University
ClinicalTrials.gov Identifier: NCT04337658    
Other Study ID Numbers: FAVOR
First Posted: April 8, 2020    Key Record Dates
Last Update Posted: April 8, 2020
Last Verified: April 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by xuexin he, Second Affiliated Hospital, School of Medicine, Zhejiang University:
breast cancer
hormone receptor positive
human epidermal growth factor receptor 2 positive
non-visceral metastases
fulvestrant
capecitabine
trastuzumab
pertuzumab
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasm Metastasis
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplastic Processes
Pathologic Processes
Capecitabine
Trastuzumab
Fulvestrant
Pertuzumab
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antineoplastic Agents, Immunological
Antineoplastic Agents, Hormonal
Estrogen Receptor Antagonists
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs