Validation of the Genetic Signature 354849 as a Prognostic Method

NCT ID: NCT04067882

Last Updated: 2023-11-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

189 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-09-30

Study Completion Date

2024-05-30

Brief Summary

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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

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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.

Conditions

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Cervix Cancer

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Cervix cancer

Women older than 18 years with histopathological diagnosis of cervical cancer clinical stage I2-IVA, candidates to receive standard treatment with chemotherapy followed by brachytherapy.

Genetic signature

Intervention Type OTHER

The RNA will be extracted from the tumor sample with a special kit and a q-PCR will be performed. In order to quantify the genetic expression, the comparative method called Cycle threshold or Crossing point will be used.

Interventions

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Genetic signature

The RNA will be extracted from the tumor sample with a special kit and a q-PCR will be performed. In order to quantify the genetic expression, the comparative method called Cycle threshold or Crossing point will be used.

Intervention Type OTHER

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Cancerología

OTHER_GOV

Sponsor Role lead

Responsible Party

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David Cantu

Chief of clinical trials department

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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David F Cantú-deLeón, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute of Mexico

Locations

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Instituto Nacional de Cancerologia

Mexico City, Mexico City, Mexico

Site Status RECRUITING

David Cantu de Leon

Mexico City, Tlalpan, Mexico

Site Status RECRUITING

Countries

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Mexico

Central Contacts

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David F Cantú-de León, MD, MSc. PhD

Role: CONTACT

+5215537093156

Carlos G Pérez-Placencia, MSc, PhD

Role: CONTACT

Facility Contacts

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David F Cantu-de Leon, Md, PhD

Role: primary

525556280400 ext. 21016

Lenny N Gallardo-Alvarado, Md, MSc

Role: backup

525556280400 ext. 37000

David F Cantu-de Leon, MD. Msc. Phd

Role: primary

+5215537093116

Lenny N Gallardo-Alvarado, MD, Msc

Role: backup

+5215537021118

References

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Crosbie EJ, Einstein MH, Franceschi S, Kitchener HC. Human papillomavirus and cervical cancer. Lancet. 2013 Sep 7;382(9895):889-99. doi: 10.1016/S0140-6736(13)60022-7. Epub 2013 Apr 23.

Reference Type BACKGROUND
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Cohen PA, Jhingran A, Oaknin A, Denny L. Cervical cancer. Lancet. 2019 Jan 12;393(10167):169-182. doi: 10.1016/S0140-6736(18)32470-X.

Reference Type BACKGROUND
PMID: 30638582 (View on PubMed)

Bhatla N, Aoki D, Sharma DN, Sankaranarayanan R. Cancer of the cervix uteri. Int J Gynaecol Obstet. 2018 Oct;143 Suppl 2:22-36. doi: 10.1002/ijgo.12611.

Reference Type BACKGROUND
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Todo Y, Watari H. Concurrent chemoradiotherapy for cervical cancer: background including evidence-based data, pitfalls of the data, limitation of treatment in certain groups. Chin J Cancer Res. 2016 Apr;28(2):221-7. doi: 10.21147/j.issn.1000-9604.2016.02.10.

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Morris M, Eifel PJ, Lu J, Grigsby PW, Levenback C, Stevens RE, Rotman M, Gershenson DM, Mutch DG. Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med. 1999 Apr 15;340(15):1137-43. doi: 10.1056/NEJM199904153401501.

Reference Type BACKGROUND
PMID: 10202164 (View on PubMed)

Leath CA 3rd, Monk BJ. Twenty-first century cervical cancer management: A historical perspective of the gynecologic oncology group/NRG oncology over the past twenty years. Gynecol Oncol. 2018 Sep;150(3):391-397. doi: 10.1016/j.ygyno.2018.06.023. Epub 2018 Jun 27.

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Thomas GM. Improved treatment for cervical cancer--concurrent chemotherapy and radiotherapy. N Engl J Med. 1999 Apr 15;340(15):1198-200. doi: 10.1056/NEJM199904153401509. No abstract available.

Reference Type BACKGROUND
PMID: 10202172 (View on PubMed)

Lakosi F, de Cuypere M, Viet Nguyen P, Jansen N, Warlimont B, Gulyban A, Gennigens C, Seidel L, Delbecque K, Coucke P, Hermesse J, Kridelka F. Clinical efficacy and toxicity of radio-chemotherapy and magnetic resonance imaging-guided brachytherapy for locally advanced cervical cancer patients: A mono-institutional experience. Acta Oncol. 2015;54(9):1558-66. doi: 10.3109/0284186X.2015.1062542. Epub 2015 Sep 25.

Reference Type BACKGROUND
PMID: 26406152 (View on PubMed)

Chuang L, Kanis MJ, Miller B, Wright J, Small W Jr, Creasman W. Treating Locally Advanced Cervical Cancer With Concurrent Chemoradiation Without Brachytherapy in Low-resource Countries. Am J Clin Oncol. 2016 Feb;39(1):92-7. doi: 10.1097/COC.0000000000000222.

Reference Type BACKGROUND
PMID: 26398064 (View on PubMed)

Chemoradiotherapy for Cervical Cancer Meta-analysis Collaboration (CCCMAC). Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: individual patient data meta-analysis. Cochrane Database Syst Rev. 2010 Jan 20;2010(1):CD008285. doi: 10.1002/14651858.CD008285.

Reference Type BACKGROUND
PMID: 20091664 (View on PubMed)

Chemoradiotherapy for Cervical Cancer Meta-Analysis Collaboration. Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: a systematic review and meta-analysis of individual patient data from 18 randomized trials. J Clin Oncol. 2008 Dec 10;26(35):5802-12. doi: 10.1200/JCO.2008.16.4368. Epub 2008 Nov 10.

Reference Type BACKGROUND
PMID: 19001332 (View on PubMed)

Marita A, Ordeanu C, Rancea A, Nicolae T, Nagy VM. Long-term survival following neoadjuvant chemotherapy and concomitant radiochemotherapy in locally advanced cervical cancer: results of the Oncology Institute "Prof. Dr. Ion Chiricuta" experience. J Med Life. 2018 Jan-Mar;11(1):42-50.

Reference Type BACKGROUND
PMID: 29696064 (View on PubMed)

Yin KC, Lu CH, Lin JC, Hsu CY, Wang L. Treatment outcomes of locally advanced cervical cancer by histopathological types in a single institution: A propensity score matching study. J Formos Med Assoc. 2018 Oct;117(10):922-931. doi: 10.1016/j.jfma.2018.07.002. Epub 2018 Jul 17.

Reference Type BACKGROUND
PMID: 30025761 (View on PubMed)

Horikawa N, Baba T, Matsumura N, Murakami R, Abiko K, Hamanishi J, Yamaguchi K, Koshiyama M, Yoshioka Y, Konishi I. Genomic profile predicts the efficacy of neoadjuvant chemotherapy for cervical cancer patients. BMC Cancer. 2015 Oct 19;15:739. doi: 10.1186/s12885-015-1703-1.

Reference Type BACKGROUND
PMID: 26482555 (View on PubMed)

Moreno-Acosta P, Carrillo S, Gamboa O, Romero-Rojas A, Acosta J, Molano M, Balart-Serra J, Cotes M, Rancoule C, Magne N. Novel predictive biomarkers for cervical cancer prognosis. Mol Clin Oncol. 2016 Dec;5(6):792-796. doi: 10.3892/mco.2016.1055. Epub 2016 Oct 19.

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PMID: 28101358 (View on PubMed)

Chen Q, Tian WJ, Huang ML, Liu CH, Yao TT, Guan MM. Association Between HIF-1 Alpha Gene Polymorphisms and Response in Patients Undergoing Neoadjuvant Chemotherapy for Locally Advanced Cervical Cancer. Med Sci Monit. 2016 Sep 5;22:3140-6. doi: 10.12659/msm.897486.

Reference Type BACKGROUND
PMID: 27593081 (View on PubMed)

Fernandez-Retana J, Lasa-Gonsebatt F, Lopez-Urrutia E, Coronel-Martinez J, Cantu De Leon D, Jacobo-Herrera N, Peralta-Zaragoza O, Perez-Montiel D, Reynoso-Noveron N, Vazquez-Romo R, Perez-Plasencia C. Transcript profiling distinguishes complete treatment responders with locally advanced cervical cancer. Transl Oncol. 2015 Apr;8(2):77-84. doi: 10.1016/j.tranon.2015.01.003.

Reference Type BACKGROUND
PMID: 25926073 (View on PubMed)

Zwenger AO, Grosman G, Iturbe J, Leone J, Vallejo CT, Leone JP, Verdera PP, Perez JE, Leone BA. Expression of ERCC1 and TUBB3 in locally advanced cervical squamous cell cancer and its correlation with different therapeutic regimens. Int J Biol Markers. 2015 Jul 22;30(3):e301-14. doi: 10.5301/jbm.5000161.

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PMID: 26165688 (View on PubMed)

Wen YF, Cheng TT, Chen XL, Huang WJ, Peng HH, Zhou TC, Lin XD, Zeng LS. Elevated circulating tumor cells and squamous cell carcinoma antigen levels predict poor survival for patients with locally advanced cervical cancer treated with radiotherapy. PLoS One. 2018 Oct 10;13(10):e0204334. doi: 10.1371/journal.pone.0204334. eCollection 2018.

Reference Type BACKGROUND
PMID: 30303986 (View on PubMed)

Related Links

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https://gco.iarc.fr/today/home

Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I, B.F. Global Cancer Observatory: Cancer Today

http://www.who.int/news-room/fact-sheets/detail/human-papillomavirus-(hpv)-and-cervical-cancer

World Health Organitation. Human papillomavirus (HPV) and cervical cancer.

Other Identifiers

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019/018/ICI

Identifier Type: -

Identifier Source: org_study_id

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