Identification of Molecular Biomarkers for Cancer Target Therapy Efficacy

Sponsor

OmicsWay Corp. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03724097

Collaborator

Oncobox Ltd (Other), Vitamed LLC (Other), N.N. Blokhin National Medical Research Center of Oncology (Other), Kaluga Regional Clinical Oncology Center (Other), Multidisciplinary medical holding SM-Clinic (Other), Oncological Clinical Dispensary No. 1 of the Moscow City Health Department (Other)

200

Enrollment

Locations

60.5

Anticipated Duration (Months)

28.6

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Cancer	Other: RNA sequencing Other: Transcriptome analysis Drug: target drug with the score above 0,1 Drug: target drug with the score equal or below 0,1 Drug: non-target drug Drug: palliative care

Detailed Description

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

Study Design

Study Type:

Observational

Anticipated Enrollment :

200 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

Identification of Molecular Biomarkers for Cancer Target Therapy Efficacy

Actual Study Start Date :

Oct 17, 2017

Actual Primary Completion Date :

Apr 1, 2021

Anticipated Study Completion Date :

Nov 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Group 1 Patients receiving target drugs with the score value above 0,1 as monotherapy or in combination	Other: RNA sequencing Next Generation Sequencing of RNA from tumor samples, rRNA-depleted. Other Names: RNA-seq Other: Transcriptome analysis Analysis of RNA-seq data using the Oncobox algorithm. Drug: target drug with the score above 0,1 target drug with the score above 0,1
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	Other: RNA sequencing Next Generation Sequencing of RNA from tumor samples, rRNA-depleted. Other Names: RNA-seq Other: Transcriptome analysis Analysis of RNA-seq data using the Oncobox algorithm. Drug: target drug with the score equal or below 0,1 target drug with the score equal or below 0,1 Drug: non-target drug non-target drug
Group 3 Patients receiving palliative care	Other: RNA sequencing Next Generation Sequencing of RNA from tumor samples, rRNA-depleted. Other Names: RNA-seq Other: Transcriptome analysis Analysis of RNA-seq data using the Oncobox algorithm. Drug: palliative care palliative care

Arm

Intervention/Treatment

Group 1

Patients receiving target drugs with the score value above 0,1 as monotherapy or in combination

Other: RNA sequencing

Next Generation Sequencing of RNA from tumor samples, rRNA-depleted.

Other Names:

RNA-seq

Other: Transcriptome analysis

Analysis of RNA-seq data using the Oncobox algorithm.

Drug: target drug with the score above 0,1

target drug with the score above 0,1

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

Other: RNA sequencing

Next Generation Sequencing of RNA from tumor samples, rRNA-depleted.

Other Names:

RNA-seq

Other: Transcriptome analysis

Analysis of RNA-seq data using the Oncobox algorithm.

Drug: target drug with the score equal or below 0,1

target drug with the score equal or below 0,1

Drug: non-target drug

non-target drug

Group 3

Patients receiving palliative care

Other: RNA sequencing

Next Generation Sequencing of RNA from tumor samples, rRNA-depleted.

Other Names:

RNA-seq

Other: Transcriptome analysis

Analysis of RNA-seq data using the Oncobox algorithm.

Drug: palliative care

palliative care

Outcome Measures

Primary Outcome Measures

Tumor response [2 years]
Tumor response according to the results of instrumental studies
Time to progression [2 years]
Time to progression
Time to progression compared to the previous therapy lane [2 years]
Time to progression compared to the previous therapy lane

Secondary Outcome Measures

Overall survival [2 years]
Overall survival

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	OmicsWay Corp.	Walnut	California	United States	91789
2	Kaluga Regional Clinical Oncology Center	Kaluga		Russian Federation	248007
3	Oncological Clinical Dispensary No. 1 of the Moscow City Health Department	Moscow		Russian Federation	105005
4	Multidisciplinary medical holding "SM-Clinic"	Moscow		Russian Federation	109316
5	N.N. Blokhin National Medical Research Center of Oncology	Moscow		Russian Federation	115478
6	"Oncobox" Ltd.	Moscow		Russian Federation	121205
7	Vitamed LLC	Moscow		Russian Federation	121309