Validation of the Genetic Signature 354849 as a Prognostic Method

Cervix Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04067882
• Other study ID #: 019/018/ICI
• Status: Recruiting
• Start date: September 30, 2019
• Est. completion date: May 30, 2024

Study information

• Verified date: November 2023
• Source: National Institute of Cancerología
• Contact: David F Cantú-de León, MD, MSc. PhD
• Phone: +5215537093156
• Email: dfcantu[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 189
• Est. completion date: May 30, 2024
• Est. primary completion date: May 30, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cervix Cancer
• Uterine Cervical Neoplasms

Intervention

Other:
• 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.

Locations

Country	Name	City	State
Mexico	Instituto Nacional de Cancerologia	Mexico	Mexico City
Mexico	David Cantu de Leon	Mexico City	Tlalpan

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Cancerología

Country where clinical trial is conducted

Mexico, 

References & Publications (19)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Genetic signature validation	Validate the genetic signature of 27 genes to predict treatment response in patients with cervix cancer.	2 years
Secondary	Predictive values test	Determine sensitivity, specificity and predictive values.	2 years

External Links

•   Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I, B.F. Global Cancer Observatory: Cancer Today
•   World Health Organitation. Human papillomavirus (HPV) and cervical cancer.