Neoadjuvant Chemotherapy in Cervical Cancer

Phase 3

Completed

• Conditions: Cancer of the Uterine Cervix; Cervix Cancer; Cervical Cancer
• Interventions: Drug: Neoadjuvant chemotherapy

• Registration Number: NCT05384366
• Lead Sponsor: Banaras Hindu University

Brief 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).

Detailed 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.

Study Timeline

• Study Start: 2020-08-01
• Primary Completion: 2022-03-31
• Study Completion: 2022-03-31
• Status Verified: 2022-05
• Study First Submitted: 2022-05-16
• Study First Submitted QC: 2022-05-19
• Last Update Submitted: 2022-05-19
• Study First Posted: 2022-05-20
• Last Update Posted: 2022-05-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 33

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Neoadjuvant chemotherapy	Neoadjuvant chemotherapy	Patients receiving neoadjuvant paclitaxel 175mg/m2 and carboplatin (AUC5) at three weekly interval by intravenous route

Primary Outcome Measures

Name	Time	Method
Clinical Response	21 days after completion of third cycles	Response to intervention by RACIST criteria 1.1
Pathological response	6 months	Pathological response after evaluation of surgical specimen and pathological staging

Trial Locations

Locations (1)

Banaras Hindu University; 🇮🇳 Varanasi, UP, India