Adjuvant Metronomic Capecitabine Plus Endocrine Therapy for HR+/HER2- Primary Breast Cancer

NCT05063136 | Recruiting Phase 3 DMC

• 1 other identifier: HELEN-008
• Study Type: interventional
• Target: 1,979
• Locations: 1 country
• Sites: 1

Brief Summary

Breast cancer (BC) is one of most prevalent malignant tumors in the world. According to the 2020 edition of the global cancer statistics report, the incidence rate of BC has overtaken lung cancer to become the most commonly diagnosed cancer. In the past three decades, survival of patients with primary BC have been notably improved, mainly due to early detection of the disease and advances in adjuvant treatments such as endocrine therapy, chemotherapy, and anti-HER2 therapy. Patients with HR-positive and HER2-negative primary BC account for approximately 70% of all cases of early breast cancer. Endocrine therapy is the core treatment for this subtype of BC. Tamoxifen, aromatase inhibitor or their sequential administration can reduce the recurrence and mortality of this BC subtype. The results of TEXT/SOFT study showed that, compared with the traditional 5-year tamoxifen treatment, tamoxifen + OFS or aromatase inhibitor + OFS can further improve the survival of HR+/HER2- breast cancer patients. However, for premenopausal BC patients with HR+/HER2-, only 82.5% (tamoxifen plus OFS) and 85.7% (aromatase inhibitor plus OFS) of 5-year DFS were achieved. For postmenopausal BC patients, the 5-year DFS was only about 84% with aromatase inhibitors. Therefore, the survival of HR+/ HER2- BC patients needs to be further improved. Metronomic chemotherapy refers to the use of the minimum effective dose of chemotherapy drugs for long-term, uninterrupted administration to achieve anti-tumor effect. Metronomic chemotherapy has gradually been verified in clinical practice in the past 20 years. In 2020, SYSUCC-001 study has confirmed that capecitabine (650 mg/ m2 bid, for 1 years) can reduce the risk of 5-year DFS events by 36% in TNBC patients in addition to standard treatment. Besides, POTENT study has confirmed that the combination of endocrine therapy and S-1 (for one year) can further reduce the risk of iDFS by 37% in HR+/HER2- BC patients who have completed the standard treatment. Compared with capecitabine, S-1 has no indication for BC and it is not in the recommendation for BC treatment in the guidelines. Therefore, the investigators conduct this study to explore whether adjuvant Capecitabine metronomic chemotherapy for one year can further improve the survival of BC patients with HR+/ HER2- in addition to standard treatment.

Conditions

Breast Cancer

Keywords

HR-positive, Her2-negative

Outcome Measures

Primary Outcomes (1)

• Invasive disease-free survival (iDFS)

  iDFS defined as the period from the treatment allocation date to the confirmed recurrence date (excluding non-invasive ductal carcinoma, non-invasive lobular carcinoma, and all other intraepithelial carcinoma), confirmed development of cancerous lesions other than recurrence, or the date of death from any cause, whichever was the earliest.

  through study completion，an average of 5 year

Secondary Outcomes (4)

• Overall survival (OS)

  through study completion，an average of 5 year

• Distant disease-free survival (DDFS)

  through study completion，an average of 5 year

• Disease-free survival (DFS)

  through study completion，an average of 5 year

• Adverse events

  through study completion，up to 7 years

Other Outcomes (1)

• multi-gene assays as prognostic marker

  through study completion，up to 7 years

Study Arms (2)

Capecitabine+endocrine therapy

EXPERIMENTAL

capecitabine (500mg, tid) (for 1 year)+standard endocrine therapy (at least 5 years)

Drug: Capecitabine+endocrine therapy

Placebo+endocrine therapy

PLACEBO COMPARATOR

oral placebo (tid) (for 1 year) + standard endocrine therapy (at least 5 years)

Drug: Placebo+endocrine therapy

Interventions

Capecitabine+endocrine therapy DRUG

Capecitabine (500mg, tid) (for 1 year)+ standard endocrine therapy (at least 5 years)

Also known as: Experimental group

Capecitabine+endocrine therapy

Placebo+endocrine therapy DRUG

Placebo (tid) (for 1 year)+ standard endocrine therapy (at least 5 years)

Also known as: Control group

Placebo+endocrine therapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: 18-70 years old
• Women with known menstrual status (at the beginning of randomization or adjuvant endocrine therapy). Postmenopausal status is defined as (1) The patient has undergone bilateral ovariectomy, or (2) Age ≥ 60 years, or age \< 60 years, amenorrhea for 12 months or more (without chemotherapy, tamoxifen, toremifene or ovarian suppression), and follicle stimulating hormone (FSH) and plasma estradiol are within the normal range of local postmenopausal women.(3) If the patient is taking tamoxifen or toremifene and is younger than 60 years old, the FSH and plasma estradiol levels are within the postmenopausal range (Notes:For premenopausal women before the start of adjuvant chemotherapy, amenorrhea is not a reliable indicator of menopausal status. Ovarian function may be complete or restored despite anovulation/amenorrhea. For women with treatment-induced amenorrhea, continuous measurements of FSH and/or estradiol are required according to clinical guidelines to determine postmenopausal status.)
• Invasive breast cancer patients with HR (+) and HER2(-), which is confirmed by histopathology. (1) ER and/or PR positive (positive staining accounted for more than 1% of all tumor cells) (2) HER-2 negative (IHC 0, 1+, or IHC 2 + and no fish amplification)
• Patients received radical surgery and chemotherapy (neoadjuvant or adjuvant chemotherapy), and for patients who received neoadjuvant chemotherapy, at least one of the following conditions should be met: (1) Patients not achieving PCR after neoadjuvant chemotherapy; (2) Axillary lymph nodes metastasis (including micro-metastasis) were confirmed by cytology or histology before neoadjuvant chemotherapy.
• Patients who have received breast cancer treatment in the past should meet the following conditions at the same time: (1) No more than 1 year after radical mastectomy. (2) For the patients receiving adjuvant chemotherapy, the time from the last chemotherapy to the beginning of enrollment should be more than 21 days. (3) For patients receiving radiotherapy, it should be no less than 14 days from the date of last radiotherapy to the beginning of enrollment. (4) Endocrine therapy should not exceed 6 months before entering the study (calculated as 30 days per month);
• The following laboratory results should be met to determine that the patient has sufficient bone marrow and organ function: Absolute neutrophil count (ANC) ≥ 1.5 × 109/L; Platelet ≥ 100 × 109/L; hemoglobin ≥ 9.0 g / dl; Creatinine clearance rate ≥ 50ml/min; alanine aminotransferase (ALT)\< 2.5 × Upper limit of normal range (ULN); aspartate aminotransferase (AST) \< 2.5 × ULN.
• For patients receiving anthracycline chemotherapy, EF value of cardiac ultrasound was ≥ 55% within 14 days before randomization;
• If the patient is a woman of childbearing age, the serum pregnancy test was negative within 14 days before randomization.
• ECOG score was 0 or 1.
• Patient has signed informed consent voluntarily.

You may not qualify if:

• Double primary cancers in active stage (simultaneous double primary cancers and heterochronous double primary cancers with disease-free interval ≤ 5 years). Note: carcinoma in situ (intraepithelial carcinoma or lesion equivalent to mucosal carcinoma) cured by local treatment is not included in active double primary carcinoma.
• Severe Diarrhea.
• Combined with the following serious complications: (1) Uncontrolled diabetes; (2) Uncontrolled hypertension; (3) Unstable angina and arrhythmias need treatment; (4) cirrhosis and liver failure (5) Interstitial pneumonia, pulmonary fibrosis and severe emphysema; (6) Active infection; (7) Other serious complications.

Sponsors & Collaborators

• Henan Cancer Hospital: lead

Study Sites (1)

Henan cancer hospital

Zhengzhou, Henan, China

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Control Groups

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Study Officials

• Zhenzhen Liu

  Study Principal Investigator Henan Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhenzhen Liu

CONTACT

13603862755; liuzhenzhen73@163.com

Jiujun Zhu

CONTACT

13676962766; bigapple0601@126.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: September 13, 2021
• First Posted: September 30, 2021
• Study Start: September 28, 2021
• Primary Completion: September 1, 2025
• Study Completion (Estimated): September 1, 2028
• Last Updated: November 4, 2024

Record last verified: 2024-10

Locations

CN (1)