Study of Weekly Paclitaxel and Cisplatin in FIGO IB2 and IIA2 Cervical Cancer Followed by Radical Hysterectomy

Study Overview
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Brief Summary
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The purpose was to establish a quick (7-day) cycle schedule of paclitaxel (60 mg/m2) combining with cisplatin (40 mg/m2) NAC regimen could be tolerated without interfering the following surgical treatment and a favorable overall survival rate for stages IB2 and IIA2 cervical squamous cell carcinoma (SCC).

Detailed Description
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This is a multi-center, open-label, Simon's 2-stage, phase II study of paclitaxel and cisplatin as neoadjuvant therapy in patients with FIGO IB2 or IIA2, squamous cell cervical carcinoma of the uterine cervix. Primary Objectives: • Overall survival Secondary Objectives: Safety Progression-free survival Response rate Postoperative RT/CRT rate To assess Quality-of-life An estimate of 64 evaluable patients will be enrolled in this phase II investigation.

Official Title
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Phase II Study of Weekly Paclitaxel and Cisplatin in FIGO IB2 and IIA2 Cervical Cancer Followed by Radical Hysterectomy

Conditions
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Cervical Cancer

Intervention / Treatment
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* Drug: paclitaxel
* Drug: cisplatin
* Procedure: Radical hysterectomy and bilateral pelvic lymphadenectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women with previously untreated, histologically confirmed squamous cell carcinoma of the uterine cervix HPV16-positive aged 35-70 years or HPV16-negative age <55 years FIGO stage IB2 or bulky IIA, with tumor extending to the vagina within the upper one third of the vaginal wall. Bulky tumor is defined as a visible cervical tumor with the largest diameter >4 cm or (b) a cervix expanded to > 4 cm as a result of tumor infiltration by pelvic examination verified by magnetic resonance image (MRI) or 3-dimensional (D) computed tomography (CT) no suspicious extrapelvic metastasis detected by MRI or 3-D CT adequate marrow, liver and renal functions :hemoglobin level >= 10 g/dL, WBC count >= 3,000/mm3 or absolute neutrophil count >= 1,500/mm3, platelet count >= 100,000/mm3, serum transaminase (AST, ALT) levels <= 60 IU/mL, total serum bilirubin within normal range, serum creatinine level <= 1.5 mg/dL, and blood urea nitrogen level <=20 mg/dL adequate cardiopulmonary function that tolerates the administration of study regimen and radical hysterectomy Eastern Cooperative Oncology Group performance status of 0 to 1 had written informed consent to participate in the study Appropriate organ and marrow function : leukocytes >=3,000/μL absolute neutrophil count >= 1,500/μL platelets >= 100,000/μL (not platelet transfusion dependent) hemoglobin >= 10 g/dL total bilirubin within normal range AST/ALT <= 2.5 X upper limit of normal range (ULN) BUN <= 20 mg/dL serum creatinine <=1.5 mg/dL or clearance > 60 mL/min a negative urinary pregnancy test in a patient with child-bearing potential Exclusion Criteria: Patients will be excluded from the study if they meet any of the following criteria: adenocarcinoma , adenosquamous carcinoma, or small cell carcinoma concurrent or history of malignant tumor(s) other than treated nonmelanoma skin cancer had received surgical procedure other than cervical biopsy or cytotoxic procedure including chemotherapy, radiotherapy or therapy with biologic response modifier(s) for the cervical tumor enlarged pelvic lymph node with positive aspiration cytologic or histologic study participate in investigational treatment or another clinical trial for cervical cancer history of allergic reaction to platinum or paclitaxel uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements pregnant or breast feeding women

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Weekly paclitaxel and cisplatin<br>7-day cycle schedule of paclitaxel (60 mg/m2) combining with cisplatin (40 mg/m2) NAC regimen followed by radical hysterectomy and bilateral pelvic lymphadenectomy | Drug: paclitaxel<br>* 7-day cycle schedule of paclitaxel (60 mg/m2)<br>* Other names: Taxol;Drug: cisplatin<br>* 7-day cycle schedule of cisplatin (40 mg/m2)<br>* Other names: Kemoplat;Procedure: Radical hysterectomy and bilateral pelvic lymphadenectomy<br>* 2 weeks after last course of neoadjuvant chemotherapy<br>* Other names: RH-PLND;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survivial | The primary objective is to determinate the difference in 5-year survival rate of subjects with NAC+RH-PLND compared with standard CCRT. Based on the pilot research, the 5-year survival rate of NAC+RH-PLND is expected to be around 87.5%. Thus, a sample size of 64 subjects in NAC+RH-PLND group is required for correctly detecting a 12.5% difference between 5-year OS rate of NAC+RH-PLND group and a reference value 75% of standard CCRT in order to achieving an 80% power at a significance level 0.05. | January 31, 2023 (5 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety (If > 6 significant G3/4 AEs occur) | If > 6 significant G3/4 AEs occur | January 31, 2023 (up to 5 years) | 
| Response rate (Pathological response) | Pathological response will be calculated | Post-operative 1 month | 
| Postoperative RT/CRT rate | Postoperative RT/CCRT will be given to defined high-risk group | Post-operative 6 months | 
| Quality-of-life | using EORTC QLQ-C30, EORTC-QLQ-CX24 | at completion of neoadjuvant chemotherapy | 
| Progression-free survival | PFS will be evaluated using Kaplan-Meier method | January 31, 2023 (up to 5 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Paclitaxel, Cisplatin, Cervical cancer, Radical hysterectomy, Neoadjuvant