Identification of Molecular Biomarkers for Cancer Target Therapy Efficacy
试验速览
- 阶段
- 不适用
- 入组人数
- 200
- 试验地点
- 7
- 主要终点
- Tumor response
研究概览
简要总结
This is a prospective trial for a computation-based efficacy prediction method for anticancer target therapies. The original computational algorithm utilizes individual transcriptome data of a cancer sample and assesses changes at the level of gene expression and intracellular signaling pathways. By applying the database of known molecular targets of anticancer target drugs it allows to rank potential efficacies of target drugs.
详细描述
Original computational algorithm Oncobox was developed to determine molecular features of individual tumors. It represents the solution for a personalized selection of target anticancer therapies. The method is based on the analysis of gene expression profile of a cancer sample in comparison with the corresponding normal tissue biosamples in order to select the most effective molecular targets for their inhibition and, accordingly, to identify more effective target drugs for cancer treatment. Histological material obtained from cancer patients during surgery or core-needle biopsy as part of standard treatment will be used for the analysis. Total RNA extracted from the tumor material will be subjected to next-generation sequencing (NGS). By comparing transcriptome profile of the tumor sample with the profiles of the corresponding normal tissue samples the rate of molecular pathways activation/deactivation will be calculated, as well as the case-to-normal ratios for the individual gene products - molecular targets of drugs. Based on these data, each target drug will be assigned with a score reflecting its potential efficacy for each individual tumor treatment. A drug with the score value above 0.1 will be considered potentially effective, a drug with the score value equal to or below 0.1 - as potentially ineffective. Following Oncobox test, 130 target anticancer drugs will be rated according to their predicted effectiveness (see the list of eligible target drugs below). This information will be fully available to a patient and his/her doctor. The doctor will prescribe treatment according to his/her consideration, e.g. based on the standards of care and the patient's life indications. After the appointment of therapy, the patients will be divided naturally into the following three observation groups. The first group will be formed from patients receiving target drugs with the score value above 0,1 as monotherapy or in combination. The second group - patients receiving only non-target drugs or target drugs with the score value equal to or below 0,1 as monotherapy or in combination. Third group will be formed by patients receiving palliative care. Within this study, these three groups will be compared by response to the therapy according to the results of instrumental studies, by time to progression and by time to progression compared to the previous line of therapy (if any). Additionally, overall survival will be measured in all three groups.
Eligible target drugs:
- Abemaciclib (LY2835219)
- Afatinib
- Aflibercept
- Alectinib
- Alemtuzumab
- Alitretinoin
- Anastrozole
- Apalutamide, ARN-509
- Arsenic trioxide
- Atezolizumab
- Avelumab
- Axitinib
- Belinostat
- Bevacizumab
- Bexarotene
- Bicalutamide
- Binimetinib (MEK162)
- Blinatumomab
- Bortezomib
- Bosutinib
- Brentuximab vedotin
- Brigatinib
- Cabazitaxel
- Cabozantinib
- Carfilzomib
- Ceritinib (Zykadia, LDK378)
- Cetuximab
- Cobimetinib
- Crizotinib
- CYT387 (Momelotinib)
- Dabrafenib
- Daratumumab
- Dasatinib
- Degarelix
- Denileukin diftitox (Ontac)
- Denosumab
- Docetaxel
- Dovitinib
- Durvalumab
- Elotuzumab
- Encorafenib
- Enzalutamide
- Erlotinib
- Estramustine
- Everolimus
- Exemestane
- Flavopiridol (Alvociclib)
- Foretinib
- Fulvestrant
- Ganetespib (STA-9090)
- Gefitinib
- Goserelin
- Homoharringtonine (Omacetaxine mepesuccinate)
- Ibritumomab tiuxetan
- Ibrutinib
- Idelalisib
- Imatinib
- Inotuzumab ozogamicin
- Ipilimumab
- Ixabepilone
- Ixazomib (MLN9708)
- Lapatinib
- Lenalidomide
- Lenvatinib
- Letrozole
- Leuprolide
- Lomustine
- Masitinib
- Medroxyprogesterone acetate (MPA)
- Megestrol
- Methyltestosterone
- Midostaurin
- Mogamulizumab
- Moxetumomab pasudotox
- Necitumumab
- Nilotinib
- Nilutamide
- Nimotuzumab
- Nintedanib (BIBF 1120)
- Niraparib
- Nivolumab (BMS-936558)
- Obinutuzumab
- Ofatumumab
- Olaparib
- Olaratumab
- Osimertinib
- Paclitaxel
- Palbociclib
- Panitumumab
- Panobinostat
- Pazopanib
- Pembrolizumab
- Perifosine
- Pertuzumab
- Pomalidomide
- Ponatinib
- Ramucirumab (Cyramza)
- Regorafenib
- Ribociclib
- Rigosertib
- Rituximab
- Romidepsin
- Rucaparib
- Ruxolitinib
- Selumetinib
- Siltuximab
- Sonidegib (LDE225)
- Sorafenib
- Sunitinib
- Tamoxifen
- Tecemotide (Emepepimut-S, L-BLP25)
- Temozolomide
- Temsirolimus
- Thalidomide
- Tivantinib
- Tivozanib
- Toremifene
- Trametinib (Mekinst)
- Trastuzumab
- Trebananib
- Vandetanib
- Veliparib
- Vemurafenib
- Venetoclax
- Vinblastine
- Vincristine
- Vindesine
- Vinorelbine
- Vismodegib
- Vorinostat
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults, diagnosed with cancer;
- •Age 18 - 80;
- •Patients who previously received anticancer treatment within the standard care, patients for whom standard therapy was not indicated or patients refused to receive standard therapy. Patients could receive an unlimited number of treatment lines before this study;
- •Available formalin fixed, paraffin-embedded (FFPE) samples of cancer tissue. The material should be confirmed by a certified pathologist, the sample taken for the analysis should contain at least 70% of tumor cells;
- •Anticipated survival of at least 3 months since the patient's inclusion in the current investigation;
- •Patients who have signed an informed consent.
排除标准
- •Anticipated survival of less than 3 months since the patient's inclusion in the current investigation;
- •Lack of tumor biopsy material, inability to obtain a new tumor biopsy.
研究组 & 干预措施
Group 3
Patients receiving palliative care
干预措施: palliative care (Drug)
Group 3
Patients receiving palliative care
干预措施: Transcriptome analysis (Other)
Group 1
Patients receiving target drugs with the score value above 0,1 as monotherapy or in combination
干预措施: RNA sequencing (Other)
Group 1
Patients receiving target drugs with the score value above 0,1 as monotherapy or in combination
干预措施: Transcriptome analysis (Other)
Group 1
Patients receiving target drugs with the score value above 0,1 as monotherapy or in combination
干预措施: target drug with the score above 0,1 (Drug)
Group 2
Patients receiving only non-target drugs or target drugs with the score value equal to or below 0,1 as monotherapy or in combination
干预措施: RNA sequencing (Other)
Group 2
Patients receiving only non-target drugs or target drugs with the score value equal to or below 0,1 as monotherapy or in combination
干预措施: Transcriptome analysis (Other)
Group 2
Patients receiving only non-target drugs or target drugs with the score value equal to or below 0,1 as monotherapy or in combination
干预措施: target drug with the score equal or below 0,1 (Drug)
Group 2
Patients receiving only non-target drugs or target drugs with the score value equal to or below 0,1 as monotherapy or in combination
干预措施: non-target drug (Drug)
Group 3
Patients receiving palliative care
干预措施: RNA sequencing (Other)
结局指标
主要结局
Tumor response
时间窗: 2 years
Tumor response according to the results of instrumental studies
Time to progression
时间窗: 2 years
Time to progression
Time to progression compared to the previous therapy lane
时间窗: 2 years
Time to progression compared to the previous therapy lane
次要结局
- Overall survival(2 years)