We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
ClinicalTrials.gov Menu

Predicted Biomarkers of CDK4/6 Inhibitors (Palbociclib) in ER-positive Metastasis Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT04289974
Recruitment Status : Unknown
Verified February 2020 by Li Qiao, Chinese Academy of Medical Sciences.
Recruitment status was:  Recruiting
First Posted : February 28, 2020
Last Update Posted : February 28, 2020
Information provided by (Responsible Party):
Li Qiao, Chinese Academy of Medical Sciences

Brief Summary:
This is a multi-center, observational study designed to explore the regulatory mechanism of palbociclib correlative pathways in therapeutic process of breast cancer, employing next generation sequencing (NGS) on DNA and RNA. This study also monitor the clonal evolution of genes by tracing the ctDNA.

Condition or disease Intervention/treatment
Breast Cancer Drug: Palbociclib

Layout table for study information
Study Type : Observational
Estimated Enrollment : 100 participants
Observational Model: Cohort
Time Perspective: Retrospective
Official Title: An Open, Multicenter Study for the Predicted Biomarkers of CDK4/6 Inhibitors (Palbociclib) in ER-positive Metastasis Breast Cancer
Actual Study Start Date : February 14, 2019
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : April 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Group/Cohort Intervention/treatment

100 cases of patients with ER+, HER2- breast cancer, experienced resistance after first line endocrinotherapy, will be assigned participants into treatment regimen, including palbociclib combined with fulvestrant.

FFPE blocks/sections or fresh tumor tissues/biopsies will be obtained from the hospitals on the points before administration and since resistance appearance. The tissue will be sequenced by a pan-cancer DNA panel (500+ genes) and whole transcriptome sequencing (WTS).

5-10 ml peripheral blood will be collected from each patient on the points before administration, 1 month after treatment, every subsequent visit and resistance appearance. The liquid biopsy will be sequenced by a pan-cancer ctDNA panel (300+ genes).

The genomic characteristics of patients received resistance will be analyzed. The relevant pathway mechanisms will be identified.

Drug: Palbociclib
Palbociclib (125 mg PO qDay for Days 1-21 of each 28-day cycle) combined with Fulvestrant (500 mg IM on Days 1, 15, and 29, and then once monthly thereafter)
Other Name: Fulvestrant

Primary Outcome Measures :
  1. Pathway regulatory mechanism during palbociclib treatment on ER+/HER2- breast cancer. [ Time Frame: 2 year ]
    Crosstalk patterns of genetic change processes with significant correlation with treatment of palbociclib combined endocrinotherapy, assessed by DNA and RNA sequencing.

  2. Patterns of clonal changing on lesions during treatment of palbociclib combined endocrinotherapy. [ Time Frame: 2 year ]
    The evolution patterns of genetic profiles since the begining of palbociclib combined endocrinotherapy until occurance of drug resistance obtained by collecting ctDNA variations dynamically.

Secondary Outcome Measures :
  1. Genetic indicators of effect and prognosis of palbociclib combined endocrinotherapy on ER+/HER2- breast cancer. [ Time Frame: 2 year ]
    Indicator genes with measurable up/down regulated activities of ER+/HER2- breast cancer patients significantly correlated with treatment of palbociclib combined endocrinotherapy.

  2. Genetic indicators of resistance of palbociclib combined endocrinotherapy on ER+/HER2- breast cancer. [ Time Frame: 2 year ]
    Specific genetic aberrations in alternative pathways, i.e. CCND1 amplification or RB1 inactivation, before treatment of palbociclib combining with endocrinotherapy and after drug-resistance of the breast cancer patients.

Biospecimen Retention:   Samples With DNA
Formalin fixed paraffin-embedded (FFPE) tumor tissue for DNA sequencing obtained from surgical/needle biopsy; fresh or liquid nitrogen frozen tissues for RNA sequencing obtained from surgical biopsy; peripheral blood (PB) samples for ctDNA sequencing

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
metastatic breast cancer patients of ER+/HER2- with resistance of first line endocrine therapy

Inclusion Criteria:

  • women aged 18-70 years old at the time of sign informed consent
  • patients diagnosed as breast cancer with evidence supporting metastatic disease, unsuitable for radical operation or radiotherapy, with no chemotherapy indication
  • full histological or cytological assessment of ER+, HER2- breast cancer
  • refractory to the most recent endocrine therapy, or progression within 12 months of endocrine therapy
  • Eastern Cooperative Oncology Group (ECOG) performance status score 0 or 1, no refractory within recent 2 weeks
  • patients with at least 1 measuralbe lesion; lesions will be excluded if received radiotherapy, unless had confirmed progression
  • life expectancy of 12 weeks or more
  • clinical laboratory test indicators meet the following criteria:
  • PLT≥100×10^9/L
  • ANC≥1.5×10^9/L
  • Hgb≥90 g/L
  • TBil≤1.5 ULN
  • ALT and AST ≤3 ULN
  • creatinine≤1.5 ULN or creatinine clearance rate≥50 mL/min
  • patients who signed informed consents before any projects, sampling and analysis; be available of tumor tissue biopsy and liquid biopsy; be cooperative for observation period
  • patients can swallow oral drugs
  • In addition to alopecia and stable peripheral neurotoxicity below grade 2, any clinical toxicity associated with previous treatment prior to enrollment must be restored to baseline or grade 1.

Exclusion Criteria:

  • no prior treatment
  • receiving treatment other than the trial 4 weeks prior to the study, or participating in another clinical study
  • unwilling to provide tissue and blood for genetic testing
  • non-resistant on endocrine therapy before treating with palbociclib
  • progress of ≥ 2nd line endocrine therapy
  • patients with advanced disease, symptoms, visceral spread, and life-threatening complications in the short term (including large uncontrollable spills [thoracic, pericardium, abdominal cavity], pulmonary lymphangitis, and liver involvement>50%)
  • patients with active, uncontrolled or symptomatic central nervous system metastases, cancerous meningitis or clinical signs suggesting pia mater disease, brain edema and/or tumor growth. Patients with a history of central nervous system metastasis or spinal cord compression, if they have received local treatment (such as radiation therapy, stereotactic surgery) and are clinically stable, they need to stop convulsions and steroids for at least 4 weeks before randomization.
  • patients received major surgery, chemotherapy, radiation therapy, or other anticancer treatments within 2 weeks prior to enrollment
  • diagnosis of any other malignant tumor, within 3 years prior to the enrollment, except adequately treated basal/squamous cell skin cancer or cervical carcinoma
  • assessed as not eligible to participate in the trial
  • infused whole blood without leukocytes removing within 120 days prior to sampling
  • during lactation or with positive blood or urine pregnancy test

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04289974

Layout table for location contacts
Contact: Qiao Li, MD 86-10-87788120 liqiaopumc@yahoo.cn
Contact: Binghe Xu, PHD 86-10-87788495 xubinghe@medmail.com.cn

Layout table for location information
China, Beijing
Cancer Hospital, ChineseAMS Recruiting
Beijing, Beijing, China, 100021
Contact: Qiao LI, MD    86-10-87788120    liqiaopumc@yahoo.cn   
Contact: Binghe XU, MD, PHD    86-10-87788495    xubinghe@medmail.com.cn   
Sponsors and Collaborators
Chinese Academy of Medical Sciences
Layout table for investigator information
Principal Investigator: Binghe Xu, PHD Chinese Academy of Medical Sciences
Layout table for additonal information
Responsible Party: Li Qiao, Principal Investigator, Chinese Academy of Medical Sciences
ClinicalTrials.gov Identifier: NCT04289974    
Other Study ID Numbers: LQ005
First Posted: February 28, 2020    Key Record Dates
Last Update Posted: February 28, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Li Qiao, Chinese Academy of Medical Sciences:
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Estrogen Receptor Antagonists
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action