Dose-finding Study of Weekly Paclitaxel and Cisplatin in FIGO IB2 and Bulky IIA Cervical Cancer (Chemothreapy)

This study is enrolling participants by invitation only.
Sponsor:
Collaborator:
Sinphar Pharmaceutical Co., Ltd
Information provided by:
Chang Gung Memorial Hospital
ClinicalTrials.gov Identifier:
NCT00823186
First received: January 13, 2009
Last updated: January 3, 2010
Last verified: January 2009
  Purpose

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.


Condition Intervention Phase
Cervical Cancer
Drug: Phyxol(Paclitaxel)
Phase 1

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Chang Gung Memorial Hospital:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 21
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)
Arms Assigned Interventions
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
Drug: Phyxol(Paclitaxel)

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

Other Name: phyxol(Paclitaxel)

Detailed Description:

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.

Primary Objectives:

  • 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

Secondary Objectives:

  • 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.

  Eligibility

Ages Eligible for Study:   35 Years to 70 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

women aged 35-70 years with all of the following criteria: untreated, histologically confirmed squamous cell carcinoma of the uterine cervix FIGO stage IB2 or bulky IIA, with tumor extension limited to within the upper one third of the vaginal wall. Bulky tumor is defined as (a) 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 and verified by magnetic resonance image (MRI), 3-dimensional (D) computed tomography (CT), or 3-D ultrasound study no suspicious lymph node metastasis as no enlarged lymph node or extrapelvic spread of cancer detected by MRI, or negative cytologic or histologic study of the suspicious node(s) (for those also participating PET-CT monitoring response trial, only abnormal FDG uptake in pelvic node(s) without proven nodal or extrapelvic metastasis are eligible)

Exclusion Criteria:

Histological or cytological documented pelvic lymph node or extrapelvic metastasis, concurrent or history of malignant tumor(s) other than treated nonmelanoma skin cancer had undergone surgical procedure other than cervical biopsy or had received cytotoxic procedure including chemotherapy, radiotherapy or treatment with biologic response modifier(s) for the cervical tumor participate in investigational treatment for the 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, a urinary pregnancy test must be performed on all patients who are of child-bearing potential before entering the study and the result must be negative

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  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00823186

Locations
Taiwan
Chang Gung Memorial Hospital
Tao Yuan, Lin kou, Taiwan, 333
Chang Gung Memory Hpspital
Chia Yi, Taiwan
Taipei Chang Gung Memory Hospital
Taipei, Taiwan
Sponsors and Collaborators
Chang Gung Memorial Hospital
Sinphar Pharmaceutical Co., Ltd
Investigators
Principal Investigator: HAO LIN, MD Chang Gung Memorial Hospital, Kaohsiung
  More Information

Additional Information:
No publications provided

Responsible Party: Department of Obstetrics & Gynecology, Chang Gung Memorial Hospital, Kaohsiung
ClinicalTrials.gov Identifier: NCT00823186     History of Changes
Other Study ID Numbers: 97-0365A3
Study First Received: January 13, 2009
Last Updated: January 3, 2010
Health Authority: Taiwan: Department of Health

Keywords provided by Chang Gung Memorial Hospital:
cervical carcinoma
neoadjuvant chemotherapy

Additional relevant MeSH terms:
Uterine Cervical Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Cisplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on July 09, 2014