Dalpiciclib With Endocrine Therapy for Advanced Breast Cancer After CDK4/6 Inhibitor Failure (DAWNA-FES)

NCT05861830 | Recruiting Phase 3

• 1 other identifier: PekingUMCH-FES-BC-2
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

CDK4/6 inhibitors are currently the standard treatment for female breast cancer patients with HR+ tumors. However, there is no established standard treatment for patients who experience treatment failure with CDK4/6 inhibitors. The MAINTAIN study has shown clinical benefits by switching to Ribociclib and changing endocrine therapy after progression on CDK4/6 inhibitors. We hypothesize that combining Dalpiciclib with physician-selected endocrine therapy, following treatment failure with CDK4/6 inhibitors, would similarly lead to improved patient survival. In this study, 18F-FES PET/CT will be employed as a non-invasive alternative to biopsy techniques for evaluating the expression of ER in various systemic lesions of the patients.

Conditions

Advanced Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Investigator-assessed PFS

  The time from the initiation of treatment to the first radiographic assessment of disease progression (PD) or any event leading to death

  Up to approximately 24 months

Secondary Outcomes (3)

• Objective Response Rate (ORR)

  Up to approximately 24 months

• Disease Control Rate (DCR)

  Up to approximately 24 months

• Overall Survival (OS)

  Up to approximately 24 months

Study Arms (2)

Arm A

EXPERIMENTAL

The combination of Dalpiciclib with physician-selected endocrine therapy

Drug: The combination of Dalpiciclib with physician-selected endocrine therapy

Arm B

ACTIVE COMPARATOR

Chemotherapy selected by the physician

Drug: Chemotherapy selected by the physician

Interventions

The combination of Dalpiciclib with physician-selected endocrine therapy DRUG

* Dalpiciclib: 150 mg, orally, once daily, on days 1-21, every 28 days (3 weeks on, 1 week off) * Letrozole: 2.5 mg, orally, once daily (continuous), every 28 days OR Anastrozole: 1.0 mg, orally, once daily (continuous), every 28 days OR Exemestane: 25 mg, orally, once daily (continuous), every 28 days OR Fulvestrant: 500 mg, intramuscular injection on day 1/15 of the first cycle, then on day 1 of each subsequent cycle, every 28 days OR Tamoxifen: 10-20 mg, orally, twice daily (continuous), every 28 days * Pre/perimenopausal women also require ovarian function suppression (OFS), which can be achieved through bilateral oophorectomy or the use of gonadotropin-releasing hormone (GnRH) analog drugs

Arm A

Chemotherapy selected by the physician DRUG

The chemotherapy regimen is chosen by the clinical physician and may include, but is not limited to, the following options: the combination of paclitaxel and capecitabine, the combination of paclitaxel and carboplatin, single-agent capecitabine, single-agent platinum drugs, and the combination of gemcitabine and platinum-based chemotherapy. Each treatment cycle consists of a 21-day duration.

Arm B

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The recent pathology results showed HR-positive and HER2-negative.
• F-FES-PET/CT showed at least one ER-positive lesion.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score: 0-2 points.
• Expected survival time ≥ 3 months.
• Previous antitumor therapy: (1) (neo)adjuvant treatment with Palbociclib or Abemaciclib or Ribociclib or relapse after adjuvant treatment with Palbociclib or Abemaciclib or Ribociclib; (2) receiving Palbociclib or Abemaciclib or Ribociclib-based treatment in the context of metastatic breast cancer or disease progression after treatment; (3) previously received ≤1 line of chemotherapy for recurrent or metastatic breast cancer; (4) previously received ≤3 lines of endocrine therapy for recurrent or metastatic breast cancer.
• Willing to undergo 18F-FDG PET/CT standard imaging.
• At least one measurable lesion outside the skull according to RECIST V1.1.
• The function of important organs meets the requirements.
• The subjects have recovered from any adverse event related to previous tumor treatment (≤ Grade 1) before the first administration of the investigational drug.

You may not qualify if:

• F-FES-PET/CT shows that all lesions are ER-negative.
• Previously received treatment with Dalpiciclib.
• MRI or lumbar puncture confirms leptomeningeal metastasis.
• Imaging confirms central nervous system metastasis.
• Participants with visceral crisis, rapid disease progression, and patients not suitable for endocrine therapy.
• Participants with ascites, baseline pleural effusion with clinical symptoms, and pericardial effusion requiring drainage within the first 4 weeks of treatment.
• Unable to swallow, intestinal obstruction, or other factors that affect drug administration and absorption.
• Participants diagnosed with any other malignancy within the past 5 years, excluding non-melanoma skin cancer treated with curative intent. Basal cell or squamous cell skin cancer, or cervical intraepithelial neoplasia and papillary thyroid cancer.
• Participants who have undergone major surgery or suffered a major injury within 4 weeks before starting treatment, or are expected to undergo major surgical treatment.
• Known history of allergy to the components of this treatment regimen.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead
• Jiangsu HengRui Medicine Co., Ltd.: collaborator

Study Sites (1)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

RECRUITING

Study Officials

• Qiang Sun, M.D.

  Peking Union Medical College Hospital

  STUDY CHAIR

Central Study Contacts

Bo Pan, M.D.

CONTACT

+86-133-6617-1269; panbopumc@163.com

Qiang Sun, M.D.

CONTACT

sunqiang_pumc@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2023
• First Posted: May 17, 2023
• Study Start: May 15, 2023
• Primary Completion: December 31, 2025
• Study Completion (Estimated): June 30, 2026
• Last Updated: March 12, 2024

Record last verified: 2024-03

Locations

CN (1)