Molecular Phenotype Changes and Personalized Treatment for CRPC

NCT02208583 | Unknown DMC

• 1 other identifier: E2014064
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

To explore the molecular phenotypic changes and personalized treatment in castration-resistant prostate cancer.

Conditions

Hormone Refractory Prostate Cancer

Keywords

Molecular phenotypic；CRPC; personalized treatment

Outcome Measures

Primary Outcomes (2)

• Molecular phenotypic changes after acquired resistance of hormonal therapy

  The acquired resistance criteria is based on the european criteria for castration resistant prostate cancer.The molecular phenotypic changes including the following observations:1.histopathologic analysis for rebiopsy pathology in CRPC;2.Immunohistochemical staining for androgen receptor(AR),Ki-67,cluster of differentiation 56(CD56),Syn,P53, AURKA,N-myc,retinoblastoma susceptibility(RB), E-cadherin, vimentin;3.Targeting exom sequencing by TruSeq Amplicon Cancer Panel(TSACP) including the hotspot mutation for 48 cancer related genes.

  24 months

• clinical progression free survival(cPFS)

  cPFS is defined as the time from the start of treatment to disease progression.

  24months

Secondary Outcomes (2)

• Overall Survival(OS)

  24 months

• The relationship between molecular phenotypic changes and OS

  24 months

Study Arms (2)

AR dependent CRPC

ACTIVE COMPARATOR

Assignment to Treatment Group based on druggable gene mutations analysis: CRPC patients without druggable gene mutations: Docetaxel \& Prednisone; CRPC patients with druggable gene mutations: DP \& Targeted drugs

Drug: Docetaxel & Prednisone; Drug: DP & Targeted drugs

AR independent CRPC

ACTIVE COMPARATOR

Assignment to Treatment Group based on druggable gene mutations analysis: CRPC patients without druggable gene mutations: cisplatin \& Etoposide; CRPC patients with druggable gene mutations: EP \& Targeted drugs

Drug: cisplatin & Etoposide; Drug: EP & Targeted drugs

Interventions

Docetaxel & Prednisone DRUG

Docetaxel \& Prednisone: Docetaxel 75mg/m2，d1;Prednisone 5mg，bid，d1-21

Also known as: Taxotere

AR dependent CRPC

DP & Targeted drugs DRUG

Docetaxel 75mg/m2，d1; Prednisone 5mg，bid，d1-21;Targeted drugs for PO. Participants with EGFR gene mutation will receive a drug called Gefitinib; Participants with BRAF gene mutations will receive a drug called Vemurafenib; Participants with AKT1 gene mutations will receive a drug called Celecoxib; Participants who have ERBB2 gene mutation will receive a drug called lapatinib; Participants with PDGFRA gene mutations will receive a drug called sunitinib; Participants with PIK3CA gene mutations will receive a drug called Everolimus

Also known as: Targeted drugs for PO

AR dependent CRPC

cisplatin & Etoposide DRUG

cisplatin \& Etoposide:cisplatin 25mg/m2，d1-3; Etoposide 100 mg/m2，d1-3

Also known as: cisplatin and Etoposide for injection

AR independent CRPC

EP & Targeted drugs DRUG

cisplatin 25mg/m2，d1-3; Etoposide 100 mg/m2，d1-3; Targeted drugs for po. Participants with EGFR gene mutation will receive a drug called Gefitinib; Participants with BRAF gene mutations will receive a drug called Vemurafenib; Participants with AKT1 gene mutations will receive a drug called Celecoxib; Participants who have ERBB2 gene mutation will receive a drug called lapatinib; Participants with PDGFRA gene mutations will receive a drug called sunitinib; Participants with PIK3CA gene mutations will receive a drug called Everolimus

Also known as: Targeted drugs for po

AR independent CRPC

Eligibility Criteria

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

You may qualify if:

• Years and older;
• patients with CRPC according to European Association of Urology diagnostic criteria ;
• vital organs functions including bone marrow, heart, liver, kidney are normal;
• complete pathological specimens including newly diagnosed with prostate cancer and disease progress to CRPC: ① biopsies or surgical specimens (tissue bank or wax block preserved specimens) at diagnosis ; ② re-biopsy specimens,transurethral prostatectomy (TURP) specimens, metastases palliative surgical specimens (tissue bank or wax block preserved specimens) after progress to CRPC; ③ amount sufficient sample for DNA extraction and quality control by up to standard (a) Sample type: None RNA degradation and pollution-free DNA samples; (b) the amount of the sample (single): ≥ 250ng (using agilent liquid platform); (c) sample concentration: ≥ 50 ng / μl (using agilent liquid platform); (d) sample purity: OD 260/280 = 1.8 \~ 2.0 );
• Then we perform following tests when patients meet the above criteria: ①Histological analysis: Hematoxylin-eosin(HE) staining ②immunohistochemistry(IHC) staining ③ 48 carcinomas associated exon sequencing
• After performing the above test, enter treatment group ① Docetaxel \& Prednisone(DP) : with high PSA and no gene mutation; ② DP + targeted drugs: with high PSA and gene mutations; ③ cisplatin \& Etoposide(EP) : low PSA and no gene mutation; ④ EP + targeted drug: Low PSA and gene mutations.
• All patients enrolled in draw peripheral blood samples 7.5ml and detect circulating tumor cells (CTC) , monitoring efficacy.
• \. Willing and able to comply with the program during the study period. 9 before entering clinical trials to provide written informed consent form, and the patient has to know you can withdraw from the study at any time in the study, and without any loss.
• \. Agrees to provide blood and tissue specimens. 11 expected survival of\> 6 months 12.Karnofsky performance status (KPS)\> 60; Eastern Cooperative Oncology Group(ECOG) score 0-2 13 signed informed consent form

You may not qualify if:

• other cancers
• cognitive inability and mental abnormalities
• other serious disease or condition
• severe, uncontrolled internal medicine and infectious diseases
• severe digestive disorder can not control
• severe electrolyte imbalance
• active disseminated intravascular coagulation
• major organ failure, such as decompensated heart, lung, liver, kidney failure
• peripheral neuropathy symptoms, NCI grade\> Ⅱ degree
• can not tolerate chemotherapy or refuse chemotherapy
• using the other test drug or participate other clinical trials
• can not oral drugs
• receiving chemotherapy, biological therapy, or other anti-cancer medicine intervals less than 4 weeks
• Researchers believe patients unsuitable (compliance, we should not follow-up)

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead

Study Sites (1)

Department of Interventional Oncology, Tianjin Medical University Cancer Institute and Hospital

Tianjin, Tianjin Municipality, 300060, China

RECRUITING

MeSH Terms

Interventions

Docetaxel; Prednisone; PE regimen; Cisplatin; Etoposide; Injections

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Glucosides; Glycosides; Carbohydrates; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Wang HaiTao, Ph.D

  Department of Interventional Oncology, Tianjin Medical University Cancer Institute and Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wang HaiTao, Ph.D

CONTACT

+86-18630955984; peterrock2000@126.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2014
• First Posted: August 5, 2014
• Study Start: June 1, 2014
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: August 5, 2014

Record last verified: 2014-06

Locations

CN (1)