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

Sponsor
Henan Cancer Hospital (Other)
Overall Status
Recruiting
CT.gov ID
NCT05063136
Collaborator
(none)
1,979
1
2
83.1
23.8

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Capecitabine+endocrine therapy
  • Drug: Placebo+endocrine therapy
Phase 3

Study Design

Study Type:
Interventional
Anticipated Enrollment :
1979 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Prevention
Official Title:
Adjuvant Capecitabine Metronomic Chemotherapy Plus Endocrine Therapy for HR-positive, HER2-negative, Primary Breast Cancer: a Multicenter, Randomized, Double-blind Phase III Clinical Trial
Actual Study Start Date :
Sep 28, 2021
Anticipated Primary Completion Date :
Sep 1, 2024
Anticipated Study Completion Date :
Sep 1, 2028

Arms and Interventions

Arm Intervention/Treatment
Experimental: Capecitabine+endocrine therapy

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

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

Placebo Comparator: Placebo+endocrine therapy

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

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

Outcome Measures

Primary Outcome Measures

  1. Invasive disease-free survival (iDFS) [through study completion,an average of 5 year]

    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.

Secondary Outcome Measures

  1. Overall survival (OS) [through study completion,an average of 5 year]

    OS: defined as the period from the date of allocation to the date of death from any cause

  2. Distant disease-free survival (DDFS) [through study completion,an average of 5 year]

    DDFS defined as the period from the date of allocation to the date on which the patient was diagnosed with distant recurrence, or the date of death from any cause

  3. Disease-free survival (DFS) [through study completion,an average of 5 year]

    DFS defined as the period from the date of treatment allocation to the date on which recurrence was confirmed, the date on which the development of cancerous lesions other than recurrence was confirmed, or the date of death from any cause, whichever was the earliest

  4. Adverse events [through study completion,up to 7 years]

    The incidence and severity of adverse events will be evaluated according to CTCAE 4.0

Other Outcome Measures

  1. multi-gene assays as prognostic marker [through study completion,up to 7 years]

    To measure expression of genes related to immune infiltration, cell proliferation and Angiogenesis, and to develop prognostic markers in relation to clinical benefit of metronomic Capecitabine

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 70 Years
Sexes Eligible for Study:
Female
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  1. Age: 18-70 years old

  2. 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.)

  3. 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)

  4. 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.

  5. 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);

  6. 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.

  7. For patients receiving anthracycline chemotherapy, EF value of cardiac ultrasound was ≥ 55% within 14 days before randomization;

  8. If the patient is a woman of childbearing age, the serum pregnancy test was negative within 14 days before randomization.

  9. ECOG score was 0 or 1.

  10. Patient has signed informed consent voluntarily.

Exclusion Criteria:
  1. 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.

  2. Bilateral breast cancer (simultaneous/metachronous) (Notes: patients with invasive breast cancer combined with contralateral DCIS, the patient was considered eligible for inclusion if the contralateral DCIS have been removed with radical surgery)

  3. Received oral 5-FU for more than 2 weeks before treatment (Notes: patient with a history of intravenous 5-FU was considered eligible for inclusion).

  4. Severe Diarrhea.

  5. 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.

  6. Past medical history: (1) myocardial infarction within 6 months; (2) Interstitial pneumonia (For local interstitial pneumonia, it can be proved to improve after treatment. Not included in this definition). (3) History of fluorouracil allergy; (4) Pregnant and lactating women; (5) Other patients not suitable for inclusion.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Henan cancer hospital Zhengzhou Henan China

Sponsors and Collaborators

  • Henan Cancer Hospital

Investigators

  • Principal Investigator: Zhenzhen Liu, Study Principal Investigator Henan Cancer Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Liuzhenzhen, Director, Henan Cancer Hospital
ClinicalTrials.gov Identifier:
NCT05063136
Other Study ID Numbers:
  • HNCH-BC008
First Posted:
Sep 30, 2021
Last Update Posted:
Oct 13, 2021
Last Verified:
Oct 1, 2021
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Liuzhenzhen, Director, Henan Cancer Hospital
Additional relevant MeSH terms:

Study Results

No Results Posted as of Oct 13, 2021