Neoadjuvant Chemotherapy in Cervical Cancer

Cervical Cancer Clinical Trial

Official title:

To Study the Factors Affecting Treatment Responses in Patients With Uterine Cervical Carcinoma Undergoing Neoadjuvant Chemotherapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05384366
• Other study ID #: NeoCx
• Status: Completed
• Phase: Phase 3
• Start date: August 1, 2020
• Est. completion date: March 31, 2022

Study information

• Verified date: May 2022
• Source: Banaras Hindu University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Cervical cancer represents the second commonest cancer in women worldwide, with 500,000 new cases and 300,000 deaths reported yearly. Among cervical cancer cases, 80% occur in developing countries and about 70% are identified as advanced cancer. According to the International Federation of Gynecology and Obstetrics (FIGO) staging system, a locally advanced cervical cancer includes stage IB2 to IIB. Treatment modalities include radical surgery with or without adjuvant radiotherapy (RT), Neoadjuvant Chemotherapy (NAC) plus radical hysterectomy with or without adjuvant RT, and concomitant chemo radiation. Currently, platinum based concurrent chemoradiotherapy is the gold standard for locally advanced cervical carcinoma. Neoadjuvant chemotherapy has many advantages: decreasing tumor size making surgery easier with improved rate of complete resection, decreased pelvic recurrence rate significantly, decreasing rate of parametrial invasion and lymph node metastasis, better brachytherapy distribution, minimal radiation toxicity, and 15% absolute increase of 5-year survival. This study will evaluate various factors i.e. patient related (Age, Menopausal status, HPV, HIV, Comorbidities), Tumor related pathological stages (TNM), grade, lymphovascular perineural invasion, lymph nodes, extranodal extension, tumor margins including radial margin, type of tumor i.e. Adeno vs squamous, mutation profile and Treatment related factors (type of NAC, duration of NAC, no of cycles of NAC).

Description:

This is a single group prospective study to evaluate factors affecting treatment responses in uterine cervical carcinoma. All patients who will be receiving NAC followed by surgery will be included and assessed for various defined factors influencing response. Responses will be assessed by RECIST 1.1 criteria. 1. All patients of cervical growth will be evaluated. Initial clinical evaluation, biopsy and if positive, HPV DNA status will be done. On confirmation of malignancy further staging will be done by FIGO Classification. Imaging will include contrast enhanced computed tomography (CECT) abdomen or Magnetic resonance imaging (MRI) pelvis and ultrasound (USG) abdomen. Routine blood investigations, chest X-ray (CXR) and Electrocardiography (ECG) will be done. 2. In recruited patients, 3 cycles of NAC consisting of Paclitaxel (175 mg/m2) and Carboplatin (AUC5) at 21 day intervals were given. 3. Adverse reactions if any were recorded as WHO toxicity grades. 4. Evaluation of response was done after end of 2nd cycle of chemotherapy with clinical examination and Imaging (CT/MRI) by RECIST 1.1 criteria. 5. Response was divided into two groups- 1) Complete/ Partial response 2) Poor response/ Stable disease/ Progressive disease. Patients with Poor response/ stable disease/ progressive disease will undergo concurrent chemoradiation (CCRT) while patients with partial/complete response will undergo Wertheim's hysterectomy. 6. After surgery Pathological evaluation will include T, N, M, histological type, Lymphovascular invasion (LVI), Perineural invasion (PNI), Depth of Tumor Invasion, Extra nodal extension (ENE), Grade, (next generation sequencing (NGS)- Mutation Analysis. 7. Post operative external pelvic irradiation was given according to Sedlis criteria in node negative, margin negative, parametria negative cases. 8. Follow up Evaluation was done at 1, 3 & 6 months by clinical examination, Biopsy for any recurrence and Imaging (CECT or MRI pelvis) at 6 months. Follow up was continued every 3 months thereof.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: March 31, 2022
• Est. primary completion date: March 31, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 100 Years

Eligibility

Inclusion Criteria:

• • All patients receiving NACT followed by Surgery/RT and willing to give consent will be included in study
• FIGO Stage Ib/ IIa/ IIb
• Age more than 18 yrs

Exclusion Criteria:

• • FIGO Stage Ia/ III/ IV
• Patients who received treatment earlier
• Pregnant/ lactating women
• Second primary cancer

Related Conditions & MeSH terms

• Cancer of the Uterine Cervix
• Cervical Cancer
• Cervix Cancer
• Uterine Cervical Neoplasms

Intervention

Drug:
• Neoadjuvant chemotherapy
doublet of taxane and carboplatin

Locations

Country	Name	City	State
India	Banaras Hindu University	Varanasi	UP

Sponsors (1)

Lead Sponsor	Collaborator
Banaras Hindu University

Country where clinical trial is conducted

India, 

References & Publications (8)

Di Donato V, Schiavi MC, Ruscito I, Visentin VS, Palaia I, Marchetti C, Fischetti M, Monti M, Muzii L, Benedetti Panici P. Effects of Neoadjuvant Chemotherapy Plus Radical Surgery as Front Line Treatment Strategy in Patients Affected by FIGO Stage III Cervical Cancer. Ann Surg Oncol. 2016 Dec;23(Suppl 5):841-849. Epub 2016 Sep 27. — View Citation

Katsumata N, Yoshikawa H, Kobayashi H, Saito T, Kuzuya K, Nakanishi T, Yasugi T, Yaegashi N, Yokota H, Kodama S, Mizunoe T, Hiura M, Kasamatsu T, Shibata T, Kamura T; Japan Clinical Oncology Group. Phase III randomised controlled trial of neoadjuvant chemotherapy plus radical surgery vs radical surgery alone for stages IB2, IIA2, and IIB cervical cancer: a Japan Clinical Oncology Group trial (JCOG 0102). Br J Cancer. 2013 May 28;108(10):1957-63. doi: 10.1038/bjc.2013.179. Epub 2013 May 2. — View Citation

Koensgen D, Sehouli J, Belau A, Weiss M, Stope MB, Grokopf V, Eichbaum M, Ledwon P, Lichtenegger W, Zygmunt M, Köhler G, Mustea A. Clinical Outcome of Neoadjuvant Radiochemotherapy in Locally Advanced Cervical Cancer: Results of an Open Prospective, Multicenter Phase 2 Study of the North-Eastern German Society of Gynecological Oncology. Int J Gynecol Cancer. 2017 Mar;27(3):500-506. doi: 10.1097/IGC.0000000000000894. — View Citation

Osman M. The role of neoadjuvant chemotherapy in the management of locally advanced cervix cancer: a systematic review. Oncol Rev. 2014 Sep 23;8(2):250. doi: 10.4081/oncol.2014.250. eCollection 2014 Sep 23. Review. — View Citation

Rose PG. Combined-modality therapy of locally advanced cervical cancer. J Clin Oncol. 2003 May 15;21(10 Suppl):211s-217s. Review. — View Citation

Sardi JE, Giaroli A, Sananes C, Ferreira M, Soderini A, Bermudez A, Snaidas L, Vighi S, Gomez Rueda N, di Paola G. Long-term follow-up of the first randomized trial using neoadjuvant chemotherapy in stage Ib squamous carcinoma of the cervix: the final results. Gynecol Oncol. 1997 Oct;67(1):61-9. — View Citation

Singh U, Ahirwar N, Rani AK, Singh N, Sankhwar P, Qureshi S. The efficacy and safety of neoadjuvant chemotherapy in treatment of locally advanced carcinoma cervix. J Obstet Gynaecol India. 2013 Aug;63(4):273-8. doi: 10.1007/s13224-012-0342-6. Epub 2013 Mar 12. — View Citation

Takatori E, Shoji T, Omi H, Kagabu M, Miura F, Takeuchi S, Kumagai S, Yoshizaki A, Sato A, Sugiyama T. Analysis of prognostic factors for patients with bulky squamous cell carcinoma of the uterine cervix who underwent neoadjuvant chemotherapy followed by radical hysterectomy. Int J Clin Oncol. 2015 Apr;20(2):345-50. doi: 10.1007/s10147-014-0702-6. Epub 2014 May 14. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical Response	Response to intervention by RACIST criteria 1.1	21 days after completion of third cycles
Primary	Pathological response	Pathological response after evaluation of surgical specimen and pathological staging	6 months