Dalpiciclib Combined With Letrozole in HR+/HER2 - Gynecologic Solid Tumors

February 4, 2024 updated by: Fengzhi Feng

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 is a prospective, single-arm, single-center registry study to investigate 6-month progression-free survival with Dalpiciclib, a CDK4/6 kinase inhibitor, plus letrozole in patients with unresectable refractory or resistant recurrent HR-positive, HER2-negative gynecologic solid tumors." Dalpiciclib is a CDK4/6 kinase inhibitor that selectively inhibits the activity of CDK4/6 kinase, so that the complex with Cyclin D cannot phosphorylate the downstream Rb protein and prevent cells from entering the S phase from G1 phase, thereby inhibiting cell proliferation and anti-tumor effects.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100730
        • Recruiting
        • Peking Union Medical College Hospital
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dalpiciclib+letrozole
Drug: Dalpiciclib 150mg qd, d1-21, q4w Letrozole 2.5mg qd, q4w
Drug: Dalpiciclib plus letrozole
Dalpiciclib 150mg qd, d1-21, repeated once every 4 weeks. Letrozole 2.5mg qd, repeated once every 4 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
6-month PFS rate
Time Frame: From the start of randomization to 6 months
according to RECIST1.1 criteria,the percent of participant whose PFS is more than 6 months
From the start of randomization to 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival(OS)
Time Frame: up to 2 years
The time from the start of treatment with this study protocol to the time of all-cause death of patients.
up to 2 years
Progression-free survival(PFS)
Time Frame: From the start of randomization to a minimum of 1 year
Time from initiation of study protocol treatment to disease progression or death
From the start of randomization to a minimum of 1 year
Objective Response Rate（ORR）
Time Frame: From the start of randomization to a minimum of 1 year
Percentage of patients with CR/PR in the number of patients that whose tumour can be evaluated.
From the start of randomization to a minimum of 1 year
Disease Control Rate (DCR)
Time Frame: From the start of randomization to a minimum of 1 year
Percentage of patients with CR/PR/SD in the number of patients that whose tumour can be evaluated.
From the start of randomization to a minimum of 1 year
Duration of response（DOR）
Time Frame: From the start of randomization to a minimum of 1 year
The time between the onset of efficacy and confirmation of tumor progression
From the start of randomization to a minimum of 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Fengzhi Feng

Investigators

  • Principal Investigator: Zhi f Feng, PhD, Peking Union Medical College Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 17, 2023

Primary Completion (Estimated)

December 31, 2024

Study Completion (Estimated)

June 30, 2025

Study Registration Dates

First Submitted

January 9, 2024

First Submitted That Met QC Criteria

February 4, 2024

First Posted (Estimated)

February 6, 2024

Study Record Updates

Last Update Posted (Estimated)

February 6, 2024

Last Update Submitted That Met QC Criteria

February 4, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • K4823

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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