Clinical trial NCT04067882: Validation of the Genetic Signature 354849 as a Prognostic Method
Official title: Prospective Study for the Validation of the Genetic Signature 354849 to Predict the Response to Standard Treatment in Patients With Locally Advanced Cervical Cancer
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Cervix Cancer
Keywords: Genetic signature
Treatment response
Lead sponsor: National Institute of Cancerología
Sponsor class: OTHER_GOV
First posted: 2019-08-28
Enrollment: 189
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with the histopathological diagnosis of cervical cancer FIGO's clinical stage IB2-IVA.

Brief summary: This prospective study is focused on the validation of the genetic signature of 27 genes as a predictor of the response to concomitant chemotherapy treatment followed by brachytherapy in patients with locally advanced cervical cancer. The genes included are: ZNF238; SAP30; C10orf137; UHRF1; SUZ12; HMGN4; RBBP4; PPP1CB; SLFN11; FLJ39378; ENDOGL1; RECQL; TRPC1; TRIO; DNAH6; GNL3L; SLC36A2; SRP9; RPE; LDOC1L; PUS7L; CCDC89; LOC644921; PLEKHG1; FAM111B; RPRD2 y ETAA16.

Detailed description: There are several studies of genes or genetic signatures associated with the response to treatment in cervical cancer, but so far it has not been possible to standardize the use of any biomarker or biomarker signature as a predictor of the response to treatment with reproducible results. Therefore, there is still a need to develop an effective method to predict the response to chemo-radiotherapy in locally advanced cervical cancer. This prospective study included 189 patients with cervical cancer clinical stages IB2-IVA, without previous treatment.

Tumor samples will be obtained at the confirmatory diagnostic biopsy. All samples will be processed by the pathology laboratory as usual. The RNA will be extracted from the paraffin blocks with the RNeasy FFPE Kit (Qiagen) according to the manufacturer's recommendations. The RNA will be stored at -20°C until use. Quantitative PCR (qPCR) will be performed with the kit High-Capacity cDNA Reverse transcription Kit (Thermo Fisher Scientific). Primers for the 27 genes will be developed. The relative expression will be calculated using the 2- ΔΔCt method, using the expression of β-actin as a normalizing gene.

In order to obtain the prognostic score, the score assigned by the classifier for the sample will be calculated from the 2-ΔΔCt values obtained for each gene. This will be done by a computer-readable medium containing the type expression profiles related to a good and a bad response to the standard treatment.

Eligibility criteria: Inclusion Criteria:

* Women over 18 years old
* Cervical Cancer at IB2-IVA FIGO´s clinical stages
* Histology: squamous, adenosquamous or adenocarcinoma
* No previous treatment
* No distance metastases, discard by PET/CT
* Functional State ECOG (Eastern Cooperative Oncology Group) 0-2
* Candidates to receive standard chemoradiotherapy treatment followed by brachytherapy

Exclusion Criteria:

* Previous chemotherapeutic, surgical and/or radiotherapy treatment for female reproductive tract pathologies
* Previous invasive neoplasia (except non-melanoma skin cancer) unless there is complete remission of the disease of 3 years minimum.
* Previous systemic chemotherapy for the current cervical cancer.

Primary outcomes:
measure: Genetic signature validation
timeFrame: 2 years
Secondary outcomes:
measure: Predictive values test
timeFrame: 2 years
Other outcomes:
Locations:
city: Mexico
country: Mexico
facility: Instituto Nacional de Cancerologia
state: Mexico City
city: Mexico City
country: Mexico
facility: David Cantu de Leon
state: Tlalpan
Study officials:
affiliation: National Cancer Institute of Mexico
name: David F Cantú-deLeón, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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