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

Sponsor

Chang Gung Memorial Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT02432365

Collaborator

Asian Gynecologic Oncology Group (Other), Taiwanese Gynecologic Oncology Group (Other)

Enrollment

Locations

Arm

106

Duration (Months)

12.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Cervical Cancer	Drug: paclitaxel Drug: cisplatin Procedure: Radical hysterectomy and bilateral pelvic lymphadenectomy	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

64 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Feb 1, 2015

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Weekly paclitaxel and cisplatin 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 7-day cycle schedule of paclitaxel (60 mg/m2) Other Names: Taxol Drug: cisplatin 7-day cycle schedule of cisplatin (40 mg/m2) Other Names: Kemoplat Procedure: Radical hysterectomy and bilateral pelvic lymphadenectomy 2 weeks after last course of neoadjuvant chemotherapy Other Names: RH-PLND

Arm

Intervention/Treatment

Experimental: Weekly paclitaxel and cisplatin

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

7-day cycle schedule of paclitaxel (60 mg/m2)

Other Names:

Taxol

Drug: cisplatin

7-day cycle schedule of cisplatin (40 mg/m2)

Other Names:

Kemoplat

Procedure: Radical hysterectomy and bilateral pelvic lymphadenectomy

2 weeks after last course of neoadjuvant chemotherapy

Other Names:

RH-PLND

Outcome Measures

Primary Outcome Measures

overall survivial [January 31, 2023 (5 years)]
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.

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

35 Years to 70 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	Country
1	Department of Obstetrics & Gynecology, Chang Gung Memorial Hospital	Chiayi City	Taiwan
2	Department of Obstetrics & Gynecology, Chang Gung Memorial Hospital	Kaohsiung	Taiwan
3	Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital	Taichung	Taiwan
4	Department of Obstetrics & Gynecology, Chang Gung Memorial Hospital	Taipei	Taiwan
5	Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, Chang Gung Memorial Hospital Linkou Medical Center	Taoyuan	Taiwan