Cervical Cancer
Conditions
Keywords
stage IA cervical cancer, stage IB cervical cancer, stage IIA cervical cancer, stage IIB cervical cancer, stage III cervical cancer, stage IVA cervical cancer, cervical adenocarcinoma, cervical adenosquamous cell carcinoma, cervical squamous cell carcinoma
Brief summary
RATIONALE: Drugs used in chemotherapy, such as cisplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Hyperthermia therapy kills tumor cells by heating them to several degrees above body temperature. It is not yet known whether chemotherapy and radiation therapy are more effective with or without hyperthermia therapy in treating cervical cancer. PURPOSE: This randomized phase III trial compared the safety and efficacy of cisplatin and radiation therapy, together with hyperthermia therapy versus cisplatin and radiation therapy alone in the treatment of locally advanced cervical cancer.
Detailed description
OBJECTIVES: Compare local control, failure-free survival, and overall survival of patients with locally advanced carcinoma of the cervix treated with cisplatin and radiotherapy alone, versus cisplatin and radiotherapy with hyperthermia . OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, disease stage (IIB or IIIA vs IIIB or IVA) and age (\< 60 years vs ≥ 60 years). Patients are randomized to 1 of 2 treatment arms. LIMITATIONS: There are integrity issues with the currently available data, involving international institutions, in that several pieces of information relating to patient accrual and outcomes cannot be verified. Therefore, it would be inappropriate to report outcome measures for this study. Baseline measures of age and gender are reported for the entire study cohort. Participant flow is reported by treatment arm assignment, which was available for a majority of patients in the currently available data. Adverse events are reported for the entire cohort, as some adverse events could not be classified within a particular treatment arm.
Interventions
DRUGcisplatin
Given IV
PROCEDUREhyperthermia treatment
Patients undergo hyperthermia treatment over 60-90 minutes
RADIATIONbrachytherapy
Patients undergo brachytherapy for 2-3 days
RADIATIONexternal beam radiation therapy
Patients undergo external beam radiation therapy once daily on days 1-5
Sponsors
National Cancer Institute (NCI)
Northwestern University
Mark Dewhirst
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Invasive cervical carcinoma (squamous, adeno or adenosquamous histologies, small cell histology excluded) * age \>18years * International Federation of Gynecology and Obstetrics ((FIGO) stage IB2, IIA-IVA, FIGO stages IA, IB1 with positive pelvic lymph nodes or parametria either on imaging techniques or pathologically involved at the time of surgery. patients undergoing surgical removal of the cervix and uterus are not eligible, parametria either on imaging techniques or pathologically involved at the time • Performance status Eastern Cooperative Oncology Group(ECOG)/World Health Organisation (WHO) 0, 1 or \>/=70%respectively White Blood count (WBC) ≥ 3,000, platelets ≥ 100,000, Absolute Neutrophil Count (ANC) \> 1500 • serum bilirubin ≤ 1.5 times upper limit of normal, transaminase ≤ 3 times upper limit of normal calculated creatinine clearance \>60milliliters (mls)/liter ( Cockcroft) OR creatinine \</= 2.0mgs% paraaortic adenopathy absent or 1.5 centimeter (cm) in greatest dimension on Computerised Tomography (CT) or Magnetic Resonance Imaging (MRI) scan; No history of myocardial infarction in the last 6 months no symptomatic angina pectoris negative pregnancy test in patients under 50 Hemoglobin \>12.0 Gd/dl or \>7.5 mmo;/L with transfusion if needed written written informed consent
Exclusion criteria
surgical resection of the primary tumor (i.e. Total abdominal hysterectomy (TAH)/ Bilateral salpingoophorectomy (BSO) * patients with pacemakers or implanted defibrillators * patients with significant metallic foreign bodies (i.e. hip replacements, bone metallic rods,orthopedic plates, etc.) * prior radiotherapy or chemotherapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Tumor Response Rate at 4-6 Weeks Post Treatment | 3 months from start of therapy | Primary tumor response rate is the proportion of subjects achieving a best response of complete (CR) or partial (PR) responses, according to the RECIST criteria for change in sum of longest diameters. |
| Five-year Failure-free Survival | 5 Years | Five-year failure free survival (FFS) time was defined as the time from randomization until relapse/disease progression (local and/or distant) or death from any cause. Progression was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. The 5-year FFS rate is a percentage representing the fraction of randomized patients who, after 5 years, are disease free or alive. |
| Five-Year Local Recurrence-Free Survival | 5 years | Five-year local recurrence-free survival (LRFS) time was defined as the time from randomization until local progressive disease or death from any cause. Local recurrence was defined as evidence of disease progression on physical exam or radiologic study, confirmed histologically by tissue biopsy. Progression was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. The 5-year LRFS rate is a percentage representing the fraction of randomized patients who, after 5 years, do not have local progression or are alive. |
| Five-Year Overall Survival | 5 Years | Five-year overall survival (OS) time was time from date of randomization until death from any cause. The 5-year OS rate is a percentage, representing the fraction of randomized patients who, after 5 years, are still alive. |
Countries
United States
Participant flow
Recruitment details
Patients were recruited between 2003 and 2008 from seven different university hospitals and medical centers internationally. A total of 101 patients were enrolled from these institutions and randomized by institution, disease stage and age.
Pre-assignment details
Participant flow includes patients who were enrolled and randomized into the study. A third group of patients (Unavailable) was added in this participant flow to account for patients who were randomized, but whose treatment assignment was not documented in the current data.
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Due to integrity issues with the current data, baseline measurements of age and gender are reported for the entire cohort, rather than by treatment arm. Age and gender information were available in the current documentation for all 101 patients in this study. | 101 |
| Total | 101 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Missing Data | 4 | 11 | 7 |
Baseline characteristics
| Characteristic | Overall Study |
|---|---|
| Age Continuous | 50.25 years STANDARD_DEVIATION 12.15 |
| Sex: Female, Male Female | 101 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 54 / 101 |
| serious Total, serious adverse events | 10 / 101 |
Outcome results
Primary
Five-year Failure-free Survival
Five-year failure free survival (FFS) time was defined as the time from randomization until relapse/disease progression (local and/or distant) or death from any cause. Progression was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. The 5-year FFS rate is a percentage representing the fraction of randomized patients who, after 5 years, are disease free or alive.
Time frame: 5 Years
Primary
Five-Year Local Recurrence-Free Survival
Five-year local recurrence-free survival (LRFS) time was defined as the time from randomization until local progressive disease or death from any cause. Local recurrence was defined as evidence of disease progression on physical exam or radiologic study, confirmed histologically by tissue biopsy. Progression was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. The 5-year LRFS rate is a percentage representing the fraction of randomized patients who, after 5 years, do not have local progression or are alive.
Time frame: 5 years
Primary
Five-Year Overall Survival
Five-year overall survival (OS) time was time from date of randomization until death from any cause. The 5-year OS rate is a percentage, representing the fraction of randomized patients who, after 5 years, are still alive.
Time frame: 5 Years
Primary
Primary Tumor Response Rate at 4-6 Weeks Post Treatment
Primary tumor response rate is the proportion of subjects achieving a best response of complete (CR) or partial (PR) responses, according to the RECIST criteria for change in sum of longest diameters.
Time frame: 3 months from start of therapy