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

NCT04337658 | Not Yet Recruiting Phase 3

• 1 other identifier: FAVOR
• Study Type: interventional
• Target: 493
• Locations: 1 country
• Sites: 2

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.

Conditions

HER2-positive Breast Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  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.

  up to approximately 2 years

Secondary Outcomes (4)

• Overall Survival (OS)

  up to approximately 2 years

• Clinical Benefit Rate (CBR)

  up to approximately 2 years

• Duration of Clinical Benefit (DOCB)

  up to approximately 2 years

• Safety:Type incidence and severity (as graded by NCI CTCAE v 5.0)

  up to approximately 2 years

Study Arms (2)

Trastuzumab± Pertuzumab+ Fulvestrant

EXPERIMENTAL

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; Drug: Trastuzumab; Drug: Fulvestrant

Trastuzumab± Pertuzumab+ Capecitabine

ACTIVE COMPARATOR

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; Drug: Trastuzumab; Drug: Capecitabine

Interventions

Pertuzumab DRUG

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.

Also known as: Perjeta

Trastuzumab± Pertuzumab+ Capecitabine; Trastuzumab± Pertuzumab+ Fulvestrant

Trastuzumab DRUG

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.

Also known as: Herceptin

Trastuzumab± Pertuzumab+ Capecitabine; Trastuzumab± Pertuzumab+ Fulvestrant

Fulvestrant DRUG

500mg intramuscular injections at day 1, 15, 28 and 4 weeks thereafter

Also known as: Faslodex

Trastuzumab± Pertuzumab+ Fulvestrant

Capecitabine DRUG

1000mg/m2 orally Bid on day 1 to day 14 every 3 weeks until disease progression, unacceptable toxicity, withdrawal of consent, or study termination.

Also known as: Xeloda

Trastuzumab± Pertuzumab+ Capecitabine

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients provided written informed consent
• Postmenopausal or premenopausal or perimenopausal women aged 18-75 years:
• ≥60 years, or bilateral ovariectomy was previously performed, or
• \<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
• Premenopausal or perimenopausal women, willing to receive luteinizing hormone (LHRH) stimulation during the study
• Histologically or cytologically confirmed HR-positive (ER/PR≥10%), HER2-positive (IHC 3+ or ISH+) breast cancer
• 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)
• 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)
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 2
• Life expectancy \> 24 weeks
• left ventricular ejection fraction (LVEF) of 50% or higher at baseline (within 42 days before randomization)
• Previous adjuvant chemotherapy treatment is allowed
• Previous adjuvant trastuzumab treatment is allowed
• Hormone therapy must have been discontinued at least 1 month prior to recruitment

You may not qualify if:

• Primary and metastatic lesion lack of histological or cytological confirmation of HR-positive (ER/PR≥10%), HER2-positive (IHC 3+ or ISH+)
• Breast cancer with visceral metastases (liver, lung, pleura, pericardium, peritoneum, kidney, adrenal, brain or leptomeningeal metastases)
• Inflammatory breast cancer
• 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.
• Disease progression or recurrence within 12 months after neo/adjuvant endocrine therapy
• 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).
• CT or MRI confirmed the presence of brain or leptomeningeal metastases.
• 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.
• Non- visceral metastatic lesions cannot be evaluated by RECIST v1.1
• Active infection with human immunodeficiency virus (HIV) prior to first study treatment administration.
• History of participating any other clinical trials within 30 days prior to randomization
• Known hypersensitivity (Grade 3 or 4) to Pertuzumab, Trastuzumab, Fulvestrant or Capecitabine or the excipients of any of the trial drugs
• Pregnancy or lactation
• Uncontrolled illnesses including symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia requiring therapy, myocardial infarction within the past 6 months, or active infection
• severe pulmonary and renal disease

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (2)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510000, China

Location

Second Affiliated Hospital, Zhejiang University, School of Medicine

Hangzhou, Zhejiang, 310000, China

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

pertuzumab; Trastuzumab; Fulvestrant; Capecitabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Xuexin He, MD

  The Second Affiliated Hospital of Zhejiang University School of Medicine (SAHZU)

  PRINCIPAL INVESTIGATOR

• Jiajia Huang, MD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xuexin He, MD

CONTACT

+8618329139569; xuexinhe@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• 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: January 11, 2020
• First Posted: April 8, 2020
• Study Start: July 1, 2020
• Primary Completion: April 30, 2024
• Study Completion: April 30, 2026
• Last Updated: April 8, 2020

Record last verified: 2020-04

Locations

CN (2)