Efficacy and Safety of Dalpiciclib Plus Toremifene in the Treatment of Advanced First-line HR Positive and HER2 Negative Breast Cancer: a Multicenter, Single Arm, Exploratory Phase II Clinical Study

NCT06495515 | Not Yet Recruiting Phase 2

• 1 other identifier: Tianjin Cancer Hospital...
• Study Type: interventional
• Target: 36
• Locations: 0 countries
• Sites: N/A

Brief Summary

Experimental population:Advanced first-line HR+, HER2 metastatic breast cancer patients Research endpoint: Main research endpoint: PFS evaluated by researchers (according to RECIST 1.1 standard) Secondary study endpoint: ORR、CBR、DCR、OS The incidence of adverse events (AE) and severe adverse events (SAE) Exploratory study endpoint: Tumor infiltrating lymphocytes (sTIL) Peripheral blood lymphocyte ratio Distribution of fecal microbiota Research overall design:This study adopts a prospective, single arm design, and plans to include 36 postmenopausal or premenopausal/perimenopausal patients with metastatic breast cancer who are HR positive and HER2 negative, and receive maintenance treatment with darcy plus toremifene. In this study, the screening period did not exceed 28 days. After completing the screening examination and evaluation, eligible subjects entered the study treatment period and received maintenance treatment with darcilib combined with toremifen, for a period of 4 weeks until disease progression, intolerable toxicity, withdrawal of informed consent, or termination of medication as determined by the investigator. Conduct research according to the plan regulations Treatment and visits. Perform tumor imaging evaluation every 2 cycles (8 weeks ± 7 days) during the first 13 treatment cycles (52 weeks) of the treatment period; Afterwards, tumor imaging evaluation will be conducted every 3 cycles (12 weeks ± 7 days). Subjects should visit the research center at the end of treatment/withdrawal from the study to complete corresponding safety checks and imaging evaluations; And visit the research center 28 days after the last treatment to complete the corresponding safety assessment.

Conditions

CANCER; BRAEST CANCER; Late Frontline

Outcome Measures

Primary Outcomes (1)

• PFS

  The time from randomization to disease progression evaluated by researchers for patients

  30.6 months

Study Arms (1)

Treatment group

EXPERIMENTAL

Trial medication/treatment: 1. Dalpiciclib : 150mg orally, once a day, taken for 3 weeks, stopped for 1 week, with a cycle of 4 weeks. It is recommended to take medication at the same time every day, with warm water for delivery. It is recommended to do so on an empty stomach and fast for at least 1 hour before and after taking the medication. 2. Toremifen: 60mg orally, once a day If it is a premenopausal or perimenopausal patient, it is necessary to combine with OFS (OFS includes bilateral ovariectomy or GnRHa drugs). The subjects will be treated according to the study protocol until disease progression, intolerable toxicity, withdrawal of informed consent, or termination of medication as determined by the researcher

Drug: Dalpiciclib，Toremifen

Interventions

Dalpiciclib，Toremifen DRUG

1. Dalpiciclib : 150mg orally, once a day, taken for 3 weeks, stopped for 1 week, with a cycle of 4 weeks. It is recommended to take medication at the same time every day, with warm water for delivery. It is recommended to do so on an empty stomach and fast for at least 1 hour before and after taking the medication. 2. Toremifen: 60mg orally, once a day If it is a premenopausal or perimenopausal patient, it is necessary to combine with OFS (OFS includes bilateral ovariectomy or GnRHa drugs).

Treatment group

Eligibility Criteria

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

You may qualify if:

• Postmenopausal or premenopausal/perimenopausal female patients aged ≥ 18 years and ≤ 75 years old,
• Meet one of the following conditions:
• a) Previously underwent bilateral oophorectomy, or aged ≥ 60 years old; or b) Age\<60, natural postmenopausal state (defined as spontaneous cessation of regular menstruation for at least 12 consecutive months without any other pathological or physiological reasons), E2 and FSH at postmenopausal levels.
• c) Premenopausal or perimenopausal female patients can also be selected, but they must be willing to receive LHRH agonist treatment during the study period.
• ECOG PS 0-1；
• Female breast cancer patients diagnosed as HR positive and HER2 negative by pathology have evidence of local recurrence or metastasis, which is not suitable for surgical resection or radiotherapy for the purpose of cure.
• It has been diagnosed as HR positive and HER2 negative breast cancer (ER and PR ≥ 10%)
• HER2 is negative. If HER2 is expressed as 2+, in situ hybridization testing is required to confirm that the HER2 gene has not been amplified; 4. The patient\'s previous endocrine therapy must meet the following conditions:
• A) Late stage: did not receive any endocrine therapy; Progression within 12 months of receiving other endocrine treatments (except tamoxifen) in the late stage; b) Stage of adjuvant endocrine therapy: Progress over 12 months after completion of tamoxifen assisted endocrine therapy; During the use of aromatase inhibitors (treatment duration exceeding 6 months) or after completion of treatment, progress may occur.
• According to the RECIST 1.1 standard, there should be at least one measurable lesion present or only bone metastases (including osteolytic lesions or mixed osteolytic/osteogenic lesions).
• \. The functional level of organs must meet the following requirements:
• Blood routine
• ANC≥1.5×109/L；
• PLT≥90×109/L；
• Hb≥90 g/L；

You may not qualify if:

• The previous pathological diagnosis was HER2 positive breast cancer.
• Researchers determine patients who are not suitable for endocrine therapy. This includes late stage patients who have symptoms, have spread to the internal organs, and are at risk of life-threatening complications in the short term (including patients with uncontrollable exudates (chest, pericardium, abdominal cavity) through drainage or other methods, pulmonary lymphangitis, and more than 50% liver involvement).
• The patient has undergone major surgical procedures unrelated to breast cancer within 4 weeks before enrollment, or has not fully recovered from such surgical procedures.
• Patients with extensive advanced/metastatic, symptomatic visceral diseases, or known uncontrolled or symptomatic brain metastases.
• Previously used any CDK inhibitors, tamoxifen, everolimus, or drugs that inhibit the PI3K mTOR pathway for treatment. Using strong or moderate CYP3A4 and/or CYP2D6 inhibitors or inducers.
• Other malignant tumors within the past 5 years, excluding cured cervical carcinoma in situ, basal cell carcinoma of the skin, or squamous cell carcinoma of the skin.
• Have suffered from any heart disease, including: (1) angina pectoris; (2) Arrhythmias that require medication treatment or have clinical significance; (3) Myocardial infarction; (4) Heart failure; (5) Any other heart disease determined by the researcher as unsuitable for participation in this trial.
• Inability to swallow, intestinal obstruction, or other factors that affect medication administration and absorption.
• Known to be allergic to darcilib, letrozole, or any excipients.
• Pregnant and lactating female patients, female patients with fertility and positive baseline pregnancy test results, or those in the whole family Female patients of childbearing age who were unwilling to take effective contraceptive measures during the trial period.
• Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
• Other serious physical or mental illnesses or laboratory test abnormalities may increase the risk of participating in the study, or Disturb the research results and any other circumstances that the researcher deems unsuitable for participation in this study.

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead

MeSH Terms

Conditions

Neoplasms

Central Study Contacts

Xue Jing Liu

CONTACT

86-022-23340123; lxj8109@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2024
• First Posted: July 10, 2024
• Study Start: August 1, 2024
• Primary Completion: July 30, 2025
• Study Completion (Estimated): June 30, 2026
• Last Updated: July 10, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share