4 Versus 6 Courses of Adjuvant Chemotherapy in LACC Patients Previously Treated With NACT Plus Radical Surgery

February 18, 2015 updated by: Roberto Angioli, Campus Bio-Medico University

Phase II Randomized Controlled Trial on the Safety and Efficacy of 4 Versus 6 Courses of Adjuvant Chemotherapy in Locally Advanced Cervical Cancer Patients Previously Treated With Neoadjuvant Chemotherapy Plus Radical Surgery

The investigators primary outcome was to evaluate the effectiveness in term of Overall Survival (OS) and disease free interval (DFI) of two different platinum-based chemotherapic regimen (3 and 6 cycles) for treatment of Locally Advanced Cervical Cancer (LACC) (IB2-IIB) previously treated with Neoadjuvant Chemotherapy Plus Radical Surgery (NACT+RS).

The secondary outcome was to evaluate and compare safety, in term of toxicity profile, of the two treatment options.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Between February 2007 to January 2013, all patients with diagnosis of LAAC referred to the Division of Gynecologic Oncology of the Campus Bio-Medico University of Rome, were eligible for this protocol. The institutional internal review board approved the study. Inclusion criteria were: I) Patients with squamous cell, adenosquamous or adenocarcinoma of the cervix; II) Stage IB2-IIB according to the International Federation of Gynecology and Obstetrics (FIGO); III) age between 18 and 75 years; IV) Eastern Cooperative Oncology Group (ECOG) performance status 0-2; V) normal cardiac and respiratory functions; VI) absence of secondary malignancies; VII) no previous surgical, chemotherapic and/or radiotherapic treatment for secondary malignancies VIII) informed consent obtained from the patient.Exclusion criteria included: I) histological confirmation of papillary serous, mucinous, clear cell, squamous cell, mixed and undifferentiated carcinoma of the uterus; II) abnormal hepatic function (transaminases > 2.5 x upper limit, serum bilirubin > 1,5 x upper limit); III) abnormal renal function (creatinine clearance <60 mL/min and/or serum creatinine>2.0 mg/100 mL) function; IV) abnormal bone marrow function (absolute neutrophil count <1,5 x 109/L or platelet count < 100 x 109/L or hemoglobin < 9 g/dL; V) severe or uncontrolled infection, other systemic diseases or mental illness; and VI) pregnant women. Clinical staging was performed according to the NCCN criteria, and included pelvic examination, cervical biopsy, abdomen-pelvis Computed Tomography, chest X-ray; examination under anesthesia, cystoscopy and/or proctoscopy if clinically indicated (National Comprehensive Cancer Network, Clinical Practicw Guidelines in Oncology. Cervical Cancer, Version 2.2015) All patients who met inclusion and exclusion criteria were enrolled and received 3 cycles of neoadjuvant chemotherapy (NACT) every three weeks according to the scheme Cisplatin 100 mg/mq and Paclitaxel 175 mg/mq.

Complete response was defined as complete disappearance of all clinically detect able disease, determined by 2 observations not less than 4 weeks apart. Partial response was recorded as ≥50% reduction in total tumor size, determined by 2 observations not less than 4 weeks apart. No response or stable disease was defined as <50% decrease in tumor size or <25% increase in the size of one or more measurable lesions. Progressive disease was defined >25% increase in size or the appearance of new lesions.

After NACT all patients with stable or progressive disease were excluded from the protocol, all others were underwent to bilateral systematic pelvic lymph node dissection, classical radical hysterectomy and bilateral salpingo-oophorectomy. Aortic lymphadenectomy, up to the level of the inferior mesenteric artery, was reserved to patients with pelvic node disease at intraoperative examination or finding of bulky aortic nodes at the time of surgery. In case of positive aortic nodes, hysterectomy was not performed, patients were excluded from the protocol and referred to radiation oncologists. Similarly patients who presented positive surgical margins or close vaginal margins (<0.5 mm) at final pathology, were excluded from the study and referred to radiotherapist. After surgery were randomly allocated to undergo 4 or 6 cycles of chemotherapy by using a predetermined computer-generated randomisation code. In Group A, all patients received 4 cycles of adjuvant chemotherapy every three weeks according to the scheme Cisplatin 100 mg/mq and Paclitaxel 175 mg/mq.In Group B, all patients received instead 6 cycles of adjuvant chemotherapy every three weeks according to the same chemotherapic regimen. Adjuvant chemotherapy started within 28 days after surgery. Follow-up procedures included physical examination and vaginal cytology every 3 months for 2 years, then every 6 months until the 5th year according the NCCN 2015 and total body CT.

Therefore in all patients in whom there was suspicion of relapse, the total body CT was anticipated.

To assess the sample size, in agreement with the investigators experience, the investigators estimated a 20% reduction of the toxicity profile for patients who received 4 cycles of adjuvant chemotherapy compared to those who received 6 cycles (11; 19). Considering a power of 80%, to detect a statistically significant difference (alpha = 0.5; P = 0.05 Long Rank Test), 100 patients were necessary for each treatment arm.

OS and DFS curves were estimated using the Kaplan-Meier method and differences were compared by use of the log-rank test.

The comparison of other variables between two groups was evaluated using the Mann-Whitney test, the chi-square test, Fisher test. Statistical significance was set at p <0.05.

DFS, OS and recurrence rate were analyzed only in those patients who completed the study protocol; toxicity profile of the two treatment groups, however, were statistically analyzed considering all patients randomized and enrolled in the study protocol after treatment with NACT + RS.

Study Type

Interventional

Enrollment (Actual)

215

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Rome, Italy, 00128
        • Campus Bio-Medico of Rome

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • patients with squamous cell, adenosquamous or adenocarcinoma of the cervix
  • Stage IB2-IIB according to the Inyernational Federation of Gynecology and Obstetrics (FIGO)
  • age between 18 and 75 years
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • normal cardiac and respiratory functions
  • absence of secondary malignancies
  • no previous surgical, chemotherapic and/or radiotherapic treatment for secondary malignancies
  • informed consent obtained from the patient.

Exclusion Criteria:

  • histological confirmation of papillary serous, mucinous, clear cell, squamous cell, mixed and undifferentiated carcinoma of the uterus
  • abnormal hepatic function (transaminases > 2.5 x upper limit, serum bilirubin > 1,5 x upper limit)
  • abnormal renal function (creatinine clearance <60 mL/min and/or serum creatinine>2.0 mg/100 mL) function
  • abnormal bone marrow function (absolute neutrophil count <1,5 x 109/L or platelet count < 100 x 109/L or hemoglobin < 9 g/dL
  • severe or uncontrolled infection, other systemic diseases or mental illness; and
  • pregnant women. Clinical staging was performed according to the NCCN criteria, and included pelvic examination, cervical biopsy, abdomen-pelvis Computed Tomography, chest X-ray; examination under anesthesia, cystoscopy and/or proctoscopy if clinically indicated (National Comprehensive Cancer Network, Clinical Practicw Guidelines in Oncology. Cervical Cancer, Version 2.2015)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group A to administer 4 cycles
In Group A, all patients received 4 cycles of adjuvant chemotherapy every three weeks according to the scheme Cisplatin 100 mg/mq and Paclitaxel 175 mg/mq.
Drug: Cisplatin
Drug: Paclitaxel
Procedure: Group A adjuvant chemotherapy
In Group A, all patients received 4 cycles of adjuvant chemotherapy every three weeks according to the scheme Cisplatin 100 mg/mq and Paclitaxel 175 mg/mq.
Other Names:
  • 4 cycles
Experimental: Group B to administre 6 cycles
In Group B, all patients received instead 6 cycles of adjuvant chemotherapy every three weeks according to the same chemotherapic regimen.
Drug: Cisplatin
Drug: Paclitaxel
Procedure: Group B adjuvant chemotherapy
In Group B, all patients received 6 cycles of adjuvant chemotherapy every three weeks according to the scheme Cisplatin 100 mg/mq and Paclitaxel 175 mg/mq.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
overall survival
Time Frame: up to 6 years
To evaluate the effectiveness in term of overall survival of two different platinum-based chemotherapic regimen (4 and 6 cycles) for treatment of LACC (IB2-IIB) previously treated with NACT+RS.
up to 6 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
safety:to evaluate and compare safety, in term of toxicity profile, of the two adjuvant treatment options.
Time Frame: up to 6 years
up to 6 years
disease free interval
Time Frame: up to 6 years
To evaluate the effectiveness in term of disease free interval of two different platinum-based chemotherapic regimen (4 and 6 cycles) for treatment of LACC (IB2-IIB) previously treated with NACT+RS.
up to 6 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Campus Bio-Medico University

Investigators

  • Principal Investigator: Roberto Angioli, Professor, Campus Bio Medico of Rome

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2007

Primary Completion (Actual)

January 1, 2013

Study Completion (Actual)

September 1, 2014

Study Registration Dates

First Submitted

January 21, 2015

First Submitted That Met QC Criteria

February 18, 2015

First Posted (Estimate)

February 19, 2015

Study Record Updates

Last Update Posted (Estimate)

February 19, 2015

Last Update Submitted That Met QC Criteria

February 18, 2015

Last Verified

February 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CC/47 cbm

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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