Cervical Cancer
Conditions
Keywords
stage III cervical cancer, stage IVA cervical cancer, cervical squamous cell carcinoma, cervical adenocarcinoma, cervical adenosquamous cell carcinoma
Brief summary
RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Paclitaxel and cisplatin may increase the effectiveness of radiation therapy by making the tumor cells more sensitive to the radiation. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining radiation therapy with chemotherapy may kill more tumor cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of paclitaxel when given with radiation therapy and cisplatin and to see how well they work in treating patients with cancer of the cervix that has spread to the lymph nodes in the pelvis and abdomen.
Detailed description
OBJECTIVES: * Determine the toxicity of extended field radiotherapy with concurrent paclitaxel and cisplatin chemotherapy (as radiation sensitization) in patients with previously untreated carcinoma of the cervix metastatic to the para-aortic lymph nodes. * Determine the maximum tolerated dose of paclitaxel when combined with cisplatin plus extended field radiotherapy in this patient population. * Determine the effect of this treatment regimen on progression-free survival, overall survival, and site of recurrence (local vs distant) in these patients. OUTLINE: This is a multicenter, dose-escalation study of paclitaxel. Patients receive external beam radiotherapy (RT) to the para-aortic nodes and the pelvis daily for 5 weeks; RT must be completed within 8 weeks of its initiation. During or after external beam RT, intracavitary radiation is administered 1-5 times. Concurrently with external beam RT, patients receive paclitaxel IV over 1 hour followed immediately by cisplatin IV on days 1, 8, 15, 22, 29, and 36. Cohorts of 3-6 patients receive escalating doses of paclitaxel until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter or until the time of recurrence or death. PROJECTED ACCRUAL: A total of 20-40 patients will be accrued for this study within 4 years.
Interventions
DRUGcisplatin
DRUGpaclitaxel
RADIATIONbrachytherapy
RADIATIONradiation therapy
Sponsors
National Cancer Institute (NCI)
Gynecologic Oncology Group
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically proven previously untreated invasive carcinoma of the uterine cervix * Squamous cell carcinoma * Adenosquamous carcinoma * Adenocarcinoma * TNM classification stage IIIB or IVA (FIGO classification stage IB, IIA, IIB, IIIA, IIIB, or IVA) * Cytologically or histologically proven metastases to the para-aortic lymph nodes * No more than 8 weeks since diagnosis * No metastases to scalene nodes, intraperitoneal metastases, or metastases to other organs outside the radiation field at the time of original clinical and surgical staging * Negative CT scan of the chest * Patients with ureteral obstruction must be treated with stent or nephrostomy tube PATIENT CHARACTERISTICS: Age: * 18 and over Performance status: * GOG 0-2 Life expectancy: * At least 6 months Hematopoietic: * Absolute neutrophil count at least 1,500/mm\^3 * Platelet count at least 100,000/mm\^3 Hepatic: * Bilirubin no greater than 1.5 times normal * SGOT no greater than 3 times normal Renal: * Creatinine less than 2.0 mg/dL * No renal abnormalities (e.g., pelvic kidney, horseshoe kidney, or renal transplantation) requiring modification of radiation fields Other: * Not pregnant * No septicemia or severe infection * No other invasive malignancy within the past 3 years except nonmelanoma skin cancer PRIOR CONCURRENT THERAPY: Biologic therapy: * Not specified Chemotherapy: * No prior cytotoxic chemotherapy for this or other malignancy Endocrine therapy: * Not specified Radiotherapy: * No prior radiotherapy for this or other malignancy * No prior radiotherapy to pelvis or abdomen Surgery: * Not specified Other: * No other prior therapy for this malignancy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose Limiting Toxicity(DLT)/Significant Dose Delay of Paclitaxel With Cisplatin as Assessed by CTC 2.0 After 6 Cycles of Treatment | up to 21 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease-free Survival at 2 Years | 2 years | Product-limit estimate of the probability of being alive and progression-free at 24 months based on those 20 patients who were treated at the study recommended dose level (RDL) is 0.65, 95% confidence interval (0.44-0.86). Progression is defined as a 50% or greater increase in the product from any lesion documented within eight weeks for study entry or the appearance of any new lesion within eight weeks of entry into study. |
| Overall Survival at 2 Years | 2 years | Product-limit estimate of the probability of being alive at 24 months based on those 20 patients who were treated at the study recommended dose-level is 0.80, 95 % confidence interval (0.62-0.97) |
Countries
United States
Participant flow
Recruitment details
In Period I 12 patients were treated with weekly cisplatin(30-40 mg/m2) and paclitaxel(30-50 mg/m2) concurrent with extended field radiation. In Period II an additional 17 patients were treated with cisplatin 40 mg/m2 and paclitaxel 40 mg/m2 concurrent with radiation.
Pre-assignment details
All patients received whole pelvic and extended field radiation at 150 centigray per day for 30 days to the para-aortics, and 180 centigray per day for 25 days to the pelvis.
Participants by arm
| Arm | Count |
|---|---|
| Arm 1, P I Cisplatin 40 mg/m2, plus Paclitaxel 30 mg/m2 | 3 |
| Arm 2, P I Cisplatin 40 mg/m2, plus Paclitaxel 40 mg/m2 | 3 |
| Arm 2, P II Cisplatin 40 mg/m2, plus Paclitaxel 40 mg/m2 | 17 |
| Arm 3, P I Cisplatin 40 mg/m2, plus Paclitaxel 50 mg/m2 | 3 |
| Arm 4, P I Cisplatin 30 mg/m2, plus Paclitaxel 50 mg/m2 | 3 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Period I | Dose Limiting Toxicity(DLT) | 0 | 0 | 1 | 1 | 0 |
| Period II | Ureteral stent complications | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Arm 1, P I | Arm 2, P I | Arm 2, P II | Arm 3, P I | Arm 4, P I | Total |
|---|---|---|---|---|---|---|
| Age Continuous | 46.4 years STANDARD_DEVIATION 13.7 | 54.2 years STANDARD_DEVIATION 10.7 | 49.8 years STANDARD_DEVIATION 11 | 47.6 years STANDARD_DEVIATION 8.4 | 47.7 years STANDARD_DEVIATION 4 | 49.5 years STANDARD_DEVIATION 10.1 |
| Age, Customized 20-29 years | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants |
| Age, Customized 30-39 years | 1 participants | 0 participants | 1 participants | 0 participants | 0 participants | 2 participants |
| Age, Customized 40-49 years | 1 participants | 1 participants | 9 participants | 2 participants | 2 participants | 15 participants |
| Age, Customized 50-59 years | 0 participants | 1 participants | 2 participants | 1 participants | 1 participants | 5 participants |
| Age, Customized 60-69 years | 1 participants | 1 participants | 4 participants | 0 participants | 0 participants | 6 participants |
| Cell Type Adenocarcinoma NOS(not otherwise specified) | 0 participants | 1 participants | 1 participants | 0 participants | 0 participants | 2 participants |
| Cell Type Clear cell | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants | 1 participants |
| Cell Type Squamous cell | 3 participants | 2 participants | 16 participants | 2 participants | 3 participants | 26 participants |
| FIGO (International Federation of Gynecology and Obstetrics) Stage 1A - disease identified only microscopically | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| FIGO (International Federation of Gynecology and Obstetrics) Stage 1B - disease confined to cervix | 1 participants | 1 participants | 2 participants | 2 participants | 0 participants | 6 participants |
| FIGO (International Federation of Gynecology and Obstetrics) Stage 2A - no obvious parametrial involvement | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| FIGO (International Federation of Gynecology and Obstetrics) Stage 2B - obvious parametrial involvement | 2 participants | 0 participants | 4 participants | 0 participants | 1 participants | 7 participants |
| FIGO (International Federation of Gynecology and Obstetrics) Stage 3A -disease in lower 3rd of vagina not pelvic wall | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| FIGO (International Federation of Gynecology and Obstetrics) Stage 3B - disease extended to pelvic wall | 0 participants | 2 participants | 7 participants | 1 participants | 2 participants | 12 participants |
| FIGO (International Federation of Gynecology and Obstetrics) Stage 4A - disease spread to adjacent organs | 0 participants | 0 participants | 4 participants | 0 participants | 0 participants | 4 participants |
| FIGO (International Federation of Gynecology and Obstetrics) Stage 4B - disease spread to distant organs | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Region of Enrollment United States | 3 participants | 3 participants | 17 participants | 3 participants | 3 participants | 29 participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 17 Participants | 3 Participants | 3 Participants | 29 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 3 / 3 | 2 / 3 | 15 / 17 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 | 1 / 3 | 2 / 3 | 1 / 17 |
Outcome results
Primary
Dose Limiting Toxicity(DLT)/Significant Dose Delay of Paclitaxel With Cisplatin as Assessed by CTC 2.0 After 6 Cycles of Treatment
Time frame: up to 21 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1, P I | Dose Limiting Toxicity(DLT)/Significant Dose Delay of Paclitaxel With Cisplatin as Assessed by CTC 2.0 After 6 Cycles of Treatment | Complications unrelated to treatment | 0 participants |
| Arm 1, P I | Dose Limiting Toxicity(DLT)/Significant Dose Delay of Paclitaxel With Cisplatin as Assessed by CTC 2.0 After 6 Cycles of Treatment | Dose Limiting Toxicity(DLT)/Significant Dose Delay | 0 participants |
| Arm 2, P I | Dose Limiting Toxicity(DLT)/Significant Dose Delay of Paclitaxel With Cisplatin as Assessed by CTC 2.0 After 6 Cycles of Treatment | Complications unrelated to treatment | 0 participants |
| Arm 2, P I | Dose Limiting Toxicity(DLT)/Significant Dose Delay of Paclitaxel With Cisplatin as Assessed by CTC 2.0 After 6 Cycles of Treatment | Dose Limiting Toxicity(DLT)/Significant Dose Delay | 0 participants |
| Arm 3, P I | Dose Limiting Toxicity(DLT)/Significant Dose Delay of Paclitaxel With Cisplatin as Assessed by CTC 2.0 After 6 Cycles of Treatment | Complications unrelated to treatment | 0 participants |
| Arm 3, P I | Dose Limiting Toxicity(DLT)/Significant Dose Delay of Paclitaxel With Cisplatin as Assessed by CTC 2.0 After 6 Cycles of Treatment | Dose Limiting Toxicity(DLT)/Significant Dose Delay | 2 participants |
| Arm 4, P I | Dose Limiting Toxicity(DLT)/Significant Dose Delay of Paclitaxel With Cisplatin as Assessed by CTC 2.0 After 6 Cycles of Treatment | Dose Limiting Toxicity(DLT)/Significant Dose Delay | 2 participants |
| Arm 4, P I | Dose Limiting Toxicity(DLT)/Significant Dose Delay of Paclitaxel With Cisplatin as Assessed by CTC 2.0 After 6 Cycles of Treatment | Complications unrelated to treatment | 0 participants |
| Arm 2, PII | Dose Limiting Toxicity(DLT)/Significant Dose Delay of Paclitaxel With Cisplatin as Assessed by CTC 2.0 After 6 Cycles of Treatment | Complications unrelated to treatment | 1 participants |
| Arm 2, PII | Dose Limiting Toxicity(DLT)/Significant Dose Delay of Paclitaxel With Cisplatin as Assessed by CTC 2.0 After 6 Cycles of Treatment | Dose Limiting Toxicity(DLT)/Significant Dose Delay | 0 participants |
Secondary
Disease-free Survival at 2 Years
Product-limit estimate of the probability of being alive and progression-free at 24 months based on those 20 patients who were treated at the study recommended dose level (RDL) is 0.65, 95% confidence interval (0.44-0.86). Progression is defined as a 50% or greater increase in the product from any lesion documented within eight weeks for study entry or the appearance of any new lesion within eight weeks of entry into study.
Time frame: 2 years
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm 1, P I | Disease-free Survival at 2 Years | 0.65 probability |
Secondary
Overall Survival at 2 Years
Product-limit estimate of the probability of being alive at 24 months based on those 20 patients who were treated at the study recommended dose-level is 0.80, 95 % confidence interval (0.62-0.97)
Time frame: 2 years
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Arm 1, P I | Overall Survival at 2 Years | 0.80 probability |