Trial Title:
Dalpiciclib With Endocrine Therapy for Advanced Breast Cancer After CDK4/6 Inhibitor Failure (DAWNA-FES)
NCT ID:
NCT05861830
Condition:
Advanced Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
The combination of Dalpiciclib with physician-selected endocrine therapy
Description:
- 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 group label:
Arm A
Intervention type:
Drug
Intervention name:
Chemotherapy selected by the physician
Description:
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 group label:
Arm B
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.
Detailed description:
With the emergence of targeted therapies, the treatment landscape for patients with
hormone receptor-positive (HR+) and HER2-negative (HER2-) metastatic breast cancer (MBC)
is continuously evolving. The combination of cyclin-dependent kinases 4 and 6 inhibitors
(CDK4/6i) with endocrine therapy has become the standard treatment approach for
first-line therapy or treatment after progression on endocrine therapy. Multiple large
randomized studies have demonstrated that the combination of CDK4/6i and endocrine
therapy significantly improves progression-free survival (PFS) in HR+/HER2- MBC patients.
Updated analyses have also shown a significant improvement in overall survival (OS) with
the combination of endocrine therapy and either Palbociclib or Ribociclib. Currently,
regulatory agencies have approved four CDK4/6 inhibitors, namely Palbociclib,
Abemaciclib, Ribociclib, and Dalpiciclib, for the treatment of HR+/HER2- breast cancer.
All four CDK4/6 inhibitors are approved for use in combination with endocrine therapy for
advanced HR+/HER2- breast cancer. Abemaciclib has also been approved for use as adjuvant
therapy in early-stage breast cancer with HR+/HER2- subtype and high-risk recurrent
factors, as well as for the treatment of advanced breast cancer.
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. Despite the extensive clinical
experience with these drugs, our understanding of the long-term effects of CDK4/6
blockade in patients previously treated with CDK4/6 inhibitors is limited. 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.
18F-fluorodeoxyglucose (FDG) PET imaging is widely utilized in the field of oncology to
detect increased glucose metabolism activity. In the case of breast cancer, 18F-FDG
PET/CT imaging is predominantly recommended for patients with unclear staging, advanced
disease, or metastasis, when conventional imaging methods are inconclusive. On the other
hand, 18F-fluoroestradiol (FES) is an endogenous estrogen analogue that specifically
binds to estrogen receptors (ERs). Through PET imaging, FES enables dynamic,
quantitative, and non-invasive assessment of ER expression levels and distribution within
the patient's body. When combined with 18F-FDG PET or other imaging modalities, 18F-FES
PET imaging can evaluate the heterogeneity of ER expression and has the potential to
identify ER loss or dysfunction. It has been observed that 18F-FES PET exhibits good
correlation with traditional immunohistochemistry for assessing ER expression. Moreover,
published human studies have not reported any toxicity or adverse reactions associated
with 18F-FES usage. 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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- The recent pathology results showed HR-positive and HER2-negative.
- 18F-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.
Exclusion Criteria:
- 18F-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.
Gender:
All
Minimum age:
18 Years
Maximum age:
80 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Peking Union Medical College Hospital
Address:
City:
Beijing
Zip:
100730
Country:
China
Status:
Recruiting
Contact:
Last name:
Bo Pan, M.D.
Phone:
+86-133-6617-1269
Email:
panbopumc@163.com
Contact backup:
Last name:
Qiang Sun, M.D.
Email:
sunqiang_pumc@163.com
Investigator:
Last name:
Zhixin Hao, M.D.
Email:
Sub-Investigator
Investigator:
Last name:
Li Huo, M.D.
Email:
Sub-Investigator
Start date:
May 15, 2023
Completion date:
June 30, 2026
Lead sponsor:
Agency:
Peking Union Medical College Hospital
Agency class:
Other
Collaborator:
Agency:
Jiangsu HengRui Medicine Co., Ltd.
Agency class:
Industry
Source:
Peking Union Medical College Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05861830
