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

Breast Cancer Clinical Trial

Official title:

An Open, Multicenter Study for the Predicted Biomarkers of CDK4/6 Inhibitors (Palbociclib) in ER-positive Metastasis Breast Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04289974
• Other study ID #: LQ005
• Status: Recruiting
• Start date: February 14, 2019
• Est. completion date: April 2022

Study information

• Verified date: February 2020
• Source: Chinese Academy of Medical Sciences
• Contact: Qiao Li, MD
• Phone: 86-10-87788120
• Email: liqiaopumc[@]yahoo.cn
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: April 2022
• Est. primary completion date: June 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

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)

Locations

Country	Name	City	State
China	Cancer Hospital, ChineseAMS	Beijing	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Chinese Academy of Medical Sciences	OrigiMed

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathway regulatory mechanism during palbociclib treatment on ER+/HER2- breast cancer.	Crosstalk patterns of genetic change processes with significant correlation with treatment of palbociclib combined endocrinotherapy, assessed by DNA and RNA sequencing.	2 year
Primary	Patterns of clonal changing on lesions during treatment of palbociclib combined endocrinotherapy.	The evolution patterns of genetic profiles since the begining of palbociclib combined endocrinotherapy until occurance of drug resistance obtained by collecting ctDNA variations dynamically.	2 year
Secondary	Genetic indicators of effect and prognosis of palbociclib combined endocrinotherapy on ER+/HER2- breast cancer.	Indicator genes with measurable up/down regulated activities of ER+/HER2- breast cancer patients significantly correlated with treatment of palbociclib combined endocrinotherapy.	2 year
Secondary	Genetic indicators of resistance of palbociclib combined endocrinotherapy on ER+/HER2- breast cancer.	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.	2 year