Dose-finding Study of Weekly Paclitaxel and Cisplatin in FIGO IB2 and Bulky IIA Cervical Cancer (Chemothreapy)
This phase I study is designed to establish an optimal dose of paclitaxel, under a fixed cisplatin dose at 40 mg/m2, delivered every week for three weeks, as neoadjuvant therapy before radical hysterectomy in bulky (FIGO IB2 or FIGO IIA with primary tumor dimension > 4 cm) squamous cell cervical cancer. This study will be conducted at all branches of Chang Gung Memorial Hospital.
The starting dose of paclitaxel is 50 mg/m2, and will be escalated by increments of 10 mg/m2 to a maximum dose of 80 mg/m2. The drugs will be administered sequentially (paclitaxel first, followed by cisplatin) within one day every week for three cycles.
A cohort of 3 patients, who are assessable for toxicity, is treated at each dose level. Each patient receives a fixed dose of paclitaxel and cisplatin, without modification. If none of the first 3 patients experiences a dose limiting toxicity (DLT, see definition below this paragraph), then escalation to the next dose level will proceed. If one patient develops a DLT, the cohort will be expanded to 6 patients. If no more than 1 of these 6 patients experiences a DLT, then escalation to the next dose level will proceed. The maximum tolerated dose (MTD) is the highest dose level at which no more than 1 of 6 patients experience a DLT. This dose level will be considered as the recommended dose for Phase II study. Although efficacy evaluation is not the main purpose of this study, a response rate of 60%, evaluated immediately before or at surgery, in all cases who have undergone 2 cycles of therapy is preset as a requirement for further phase II study using this regimen.The primary goal of NAC in cervical cancer is to improve the feasibility of surgical treatment, radical hysterectomy, without delaying the scheduled surgery or increasing the surgical risk or morbidity. Therefore, the definition of DLT for NAC is responded to this principle, in addition to the standard dose-limiting toxicity for phase I study.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Dose Escalation Study Of Weekly Paclitaxel and Cisplatin Followed by Radical Hysterectomy in FIGO IB2 and Bulky IIA Cervical Cancer|
- to establish an optimal dose of weekly cisplatin plus paclitaxel for 3 cyclesas neoadjuvant chemotherapy (NAC) for FIGO IB2 and bulky IIA, squamous cell cervical cancer, followed by radical hysterectomy and pelvic lymphadenectomy [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
- to evaluate the toxicity of the study regimen and its impact to the radical hysterectomy after neoadjuvant chemotherapy [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]
- to evaluate the overall tumor response to the neoadjuvant chemotherapy [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]
|Study Start Date:||February 2009|
|Estimated Study Completion Date:||January 2013|
|Estimated Primary Completion Date:||January 2012 (Final data collection date for primary outcome measure)|
Experimental: Phyxol,cancer,intra vascular flow
weekly cisplatin plus paclitaxel for 3 cycles as neoadjuvant chemotherapy (NAC) for FIGO IB2 and bulky IIA, squamous cell cervical cancer followed by radical hysterectomy and pelvic lymphedectomy
Paclitaxel is 5ß,20-Epoxyl-1,2α,4,7,β 10 β,13 α-hexahydroxytax-11-en-9-one 4,10
-diacetae 2-benzoate 13-ester with (2R,3S)-N-benzoyl-3-phenylisocerine
This is a multi-center, open-label, phase I study of paclitaxel and cisplatin as neoadjuvant therapy in patients with FIGO IB2 or bulky IIA, squamous cell cervical carcinoma of the uterine cervix.
The study is mainly for the dose-finding of paclitaxel, combining with a fixed cisplatinum dose, as neoadjuvant chemotherapy on a weekly basis. The optimal dose of paclitaxel is principally defined as the highest dose that allow at least 5/6 patients, after NAC, to undergo scheduled radical hysterectomy. A subsequent toxicity assessment to evaluate the impact of this neoadjuvant chemotherapy to the recovery of the following radical hysterectomy, and efficacy assessment is set as the second purpose of this study.
- to establish an optimal dose of weekly cisplatin plus paclitaxel for 3 cycles as neoadjuvant chemotherapy (NAC) for FIGO IB2 and bulky IIA, squamous cell cervical cancer, followed by radical hysterectomy and pelvic lymphadenectomy
- to evaluate the toxicity of the study regimen and its impact to the radical hysterectomy after neoadjuvant chemotherapy
- to evaluate the overall tumor response to the neoadjuvant chemotherapy
An estimated of 8 to 21 patients will be enrolled in this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00823186
|Chang Gung Memorial Hospital|
|Tao Yuan, Lin kou, Taiwan, 333|
|Chang Gung Memory Hpspital|
|Chia Yi, Taiwan|
|Taipei Chang Gung Memory Hospital|
|Principal Investigator:||HAO LIN, MD||Chang Gung Memorial Hospital, Kaohsiung|