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

HER2-positive Breast Cancer Clinical Trial

— FAVOR  

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 Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04337658
• Other study ID #: FAVOR
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: July 1, 2020
• Est. completion date: April 30, 2026

Study information

• Verified date: April 2020
• Source: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Contact: Xuexin He, MD
• Phone: +8618329139569
• Email: xuexinhe[@]zju.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 493
• Est. completion date: April 30, 2026
• Est. primary completion date: April 30, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Breast Neoplasms
• HER2-positive Breast Cancer
• Neoplasm Metastasis

Intervention

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

Locations

Country	Name	City	State
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong
China	Second Affiliated Hospital, Zhejiang University, School of Medicine	Hangzhou	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
Second Affiliated Hospital, School of Medicine, Zhejiang University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Overall Survival (OS)	Overall survival (OS) was defined as the time from randomization to death from any cause.	up to approximately 2 years
Secondary	Clinical Benefit Rate (CBR)	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.	up to approximately 2 years
Secondary	Duration of Clinical Benefit (DOCB)	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)	up to approximately 2 years
Secondary	Safety:Type incidence and severity (as graded by NCI CTCAE v 5.0)	Seriousness and attribution to the study medications of AEs	up to approximately 2 years