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

NCT04289974 | Unknown DMC FDA Drug

• 1 other identifier: LQ005
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer

Keywords

Palbociclib; endocrinotherapy; resistance

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (2)

• Genetic indicators of effect and prognosis of palbociclib combined endocrinotherapy on ER+/HER2- breast cancer.

  2 year

• Genetic indicators of resistance of palbociclib combined endocrinotherapy on ER+/HER2- breast cancer.

  2 year

Study Arms (1)

Palbociclib+fulvestrant

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

Interventions

Palbociclib DRUG

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)

Also known as: Fulvestrant

Palbociclib+fulvestrant

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

metastatic breast cancer patients of ER+/HER2- with resistance of first line endocrine therapy

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Chinese Academy of Medical Sciences: lead
• OrigiMed: collaborator

Study Sites (1)

Cancer Hospital, ChineseAMS

Beijing, Beijing Municipality, 100021, China

RECRUITING

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

MeSH Terms

Conditions

Breast Neoplasms

Interventions

palbociclib; Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Binghe Xu, PHD

  Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Qiao Li, MD

CONTACT

86-10-87788120; liqiaopumc@yahoo.cn

Binghe Xu, PHD

CONTACT

86-10-87788495; xubinghe@medmail.com.cn

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 31, 2019
• First Posted: February 28, 2020
• Study Start: February 14, 2019
• Primary Completion: June 1, 2020
• Study Completion: April 1, 2022
• Last Updated: February 28, 2020

Record last verified: 2020-02

Locations

CN (1)