Combining Dalpiciclib and Letrozole for Treating Certain Gynecologic Cancers

A Phase II Study of the CDK4/6 Inhibitor Dalpiciclib Combined With Letrozole in Unresectable Refractory or Resistant Recurrent HR+/HER2 - Gynecologic Solid Tumors

This study is testing if combining Dalpiciclib with letrozole can help women with certain hard-to-treat gynecologic cancers live longer without their disease getting worse.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 75 Years
• Sex: Female
• Sponsor: Peking Union Medical College Hospital (other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Beijing, Beijing)
• Trial ID: NCT06243185 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of Dalpiciclib, a CDK4/6 kinase inhibitor, combined with letrozole in improving progression-free survival in women with unresectable, refractory, or resistant recurrent HR-positive, HER2-negative gynecologic solid tumors. The study is a prospective, single-arm, single-center registry that focuses on patients with specific types of ovarian and uterine cancers. The treatment aims to inhibit cell proliferation by blocking the activity of CDK4/6 kinase, which is crucial for cancer cell growth. Participants will be monitored for a duration of six months to assess the treatment's impact on disease progression.

Who should consider this trial

Good fit: Ideal candidates are female patients aged 18 to 75 with HR-positive, HER2-negative recurrent ovarian or uterine cancers that have not responded to standard treatments.

Not a fit: Patients with HER2-positive tumors or those who have not been diagnosed with HR-positive cancers may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat gynecologic cancers.

How similar studies have performed: While the specific combination of Dalpiciclib and letrozole is novel, similar approaches using CDK4/6 inhibitors have shown promise in other cancer types.

Eligibility criteria

Inclusion Criteria:

1. Female patients aged ≥18 years and ≤75 years;
2. Women with pathologically confirmed HR-positive, HER2-negative ovarian cancer or uterine tumors (including but not limited to high-grade serous ovarian cancer, low-grade serous ovarian cancer, ovarian endometrioid cancer, endometrioid cancer, low -grade endometrial stromal sarcoma, and uterine leiomyosarcoma) with evidence of focal recurrence or metastasis; Non-curative surgical resection or radiation therapy failing standard treatment, and no standard chemotherapy regimen. Er-positivity and/or PR-positive tumor cells were defined as 1% or more of all tumor cells that stained positively (as confirmed by the site investigator). Her2-negative was defined as 0/1+ on standard immunohistochemical (IHC) testing; An HER2/CEP17 ratio of less than 2.0 or a HER2 gene copy number of less than 4, as assessed by in situ hybridization (ISH), was confirmed by site investigator review.
3. Receipt of any previous systemic anticancer therapy for focal recurrent or metastatic disease.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
5. Measurable lesions meeting RECIST 1.1 criteria or bone-only metastatic lesions (including osteolytic lesions or mixed osteolytic/osteogenic lesions).
6. Adequate organ and bone marrow function, defined as neutrophil count (ANC) ≥ 1500/mm3(1.5 × 109/L) (no growth factor administration within 14 days); Platelet count (PLT) ≥ 100,000/mm3 (100 × 109/L) (no corrective therapy within 7 days); Hemoglobin (Hb) ≥ 9 g/dL (90 g/L) (no corrective therapy used within 7 days); Serum creatinine ≤ 1.5 times the upper limit of normal (ULN) or creatinine clearance ≥ 60 ml/min; Total bilirubin (BIL) ≤ 1.5 times upper limit of normal value (ULN); Aspartate aminotransferase (AST/SGOT) or alanine aminotransferase (ALT/SGPT) ≤ 2.5 times The upper limit of normal (ULN), patients with liver metastases should be ≤ 5×ULN.
7. Use of a medically approved contraceptive method (e.g., an intrauterine device, contraceptive pill, or condom) during the study treatment period and for 3 months after the end of the study treatment period for patients with potential childbearing potential; A negative serum HCG test must have been performed within 72 hours before study entry; And had to be non-lactating.
8. All acute toxic effects prior to antineoplastic therapy resolved to grade 0-1 (according to NCICTCAE version 5.0) or to the level specified in the inclusion/exclusion criteria. Other toxicities, such as alopecia, that were deemed by the investigators not to pose a safety risk to patients were excluded.
9. There is no limit to the number of previous lines of endocrine therapy.
10. The subjects voluntarily joined the study, signed the informed consent form, had good compliance, and cooperated with the follow-up.

Exclusion Criteria:

1. Previous pathological diagnosis of HER2-positive. Patients who were not candidates for endocrine therapy as judged by the investigator. "Patients were included who were symptomatic, had spread to the viscera, and were at risk for life-threatening complications in the short term (including patients with uncontrolled massive exudates \[thoracic, pericardial, abdominal\], pulmonary lymphangitis, and more than 50% liver involvement)." 3.Patients with brain metastases diagnosed by head CT or MRI. 4.Patients had received any previous CDK4/6 inhibitor therapy. 5.Major surgery, chemotherapy, radiation therapy, any investigational drug, or other anticancer treatment within 2 weeks before study entry.

6.Any other malignancy was diagnosed within 3 years before study entry, except nonmelanoma skin cancer, basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix treated with curative intent 7.Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), active hepatitis B (HBV DNA ≥1000 IU/ml), hepatitis C (positive hepatitis C antibody and HCV-RNA higher than the lower limit of detection of the assay), or co-infection with hepatitis B and C.

8.In the 6 months prior to study entry, the following occurred: Myocardial infarction, severe

or unstable angina, cardiac dysfunction of NYHA class 2 or higher, persistent arrhythmia of class 2 or higher (according to NCICTCAE, version 5.0), atrial fibrillation of any grade, coronary or peripheral artery bypass grafting, symptomatic congestive heart failure, or cerebrovascular accident (including transient ischemic attack or symptomatic pulmonary embolism).

9.Severe infection (e.g., intravenous antibiotics, antifungal, or antiviral agents according to standard practice) within 4 weeks before the first dose or unexplained fever \>38.5oC during screening/before the first dose.

10.Inability to swallow, intestinal obstruction, or other factors affecting drug administration and absorption.

11.Known allergies to letrozole or anastrozole, LHRH agonist (goserelin), SHR6390/ placebo, or any excipients.

12.Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.

13.Known history of psychotropic drug abuse or drug use. 14.Patients with other serious physical or mental illnesses or laboratory abnormalities that may increase the risk of participating in the study or interfere with the study results, and those who are considered by the investigator to be unsuitable for participation in the study

Where this trial is running

Beijing, Beijing

• Peking Union Medical College Hospital — Beijing, Beijing, China (RECRUITING)

Study contacts

• Principal investigator: Zhi f Feng, PhD — Peking Union Medical College Hospital
• Study coordinator: Xiao Shang, PhD

Conditions: Recurrent Ovarian Carcinoma