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

NCT ID: NCT04337658

Last Updated: 2020-04-08

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 493 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-01
• Study Completion Date: 2026-04-30

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.

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.

Conditions

HER2-positive Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Pertuzumab

Intervention Type: 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.

Trastuzumab

Intervention Type: 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.

Fulvestrant

Intervention Type: DRUG

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

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.

Group Type: ACTIVE_COMPARATOR

Pertuzumab

Intervention Type: 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.

Trastuzumab

Intervention Type: 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.

Capecitabine

Intervention Type: 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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Fulvestrant

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

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Perjeta; Herceptin; Faslodex; Xeloda

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Second Affiliated Hospital, School of Medicine, Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

xuexin he

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Xuexin He, MD

Role: PRINCIPAL_INVESTIGATOR

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

Jiajia Huang, MD

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-sen University

Locations

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

Second Affiliated Hospital, Zhejiang University, School of Medicine

Hangzhou, Zhejiang, China

Countries

China

Central Contacts

Xuexin He, MD

Role: CONTACT

xuexinhe@zju.edu.cn

+8618329139569 ext. 057187784818

Facility Contacts

Jiajia Huang, MD

Role: primary

Xuexin He, MD

Role: primary

xuexinhe@zju.edu.cn

+8618329139569 ext. 057187784818

Other Identifiers

FAVOR

Identifier Type: -

Identifier Source: org_study_id