Endometrial Adenocarcinoma, Endometrial Adenosquamous Carcinoma, Endometrial Clear Cell Adenocarcinoma, Endometrial Endometrioid Adenocarcinoma, Variant With Squamous Differentiation, Endometrial Serous Adenocarcinoma, Stage III Uterine Corpus Cancer
Conditions
Brief summary
Randomized phase III trial to compare the effectiveness of two combination chemotherapy regimens plus radiation therapy in treating patients who have stage III or stage IV endometrial cancer. Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one chemotherapy drug with radiation therapy may kill more tumor cells. It is not yet known which combination chemotherapy regimen plus radiation therapy is more effective for endometrial cancer.
Detailed description
OBJECTIVES: I. Compare survival and progression-free survival in patients with stage III endometrial carcinoma treated with tumor volume-directed pelvic radiotherapy with or without paraaortic radiotherapy followed by cisplatin and doxorubicin with or without paclitaxel. II. Compare short and long-term toxic effects of these treatment regimens in this patient population. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to radiotherapy field (pelvic vs extended field). Within 8 weeks after surgery, patients receive tumor volume-directed pelvic radiotherapy with or without paraaortic nodal radiotherapy once daily for 5 consecutive days for up to 16 weeks after surgery. Within 8 weeks of completing radiotherapy, patients are randomized to 1 of 2 chemotherapy treatment arms. Arm I: Patients receive doxorubicin IV over 30 minutes immediately followed by cisplatin IV over 1 hour on day 1. Patients also receive filgrastim (G-CSF) subcutaneously (SC) or pegfilgrastim on days 2-11. Arm II: Patients receive doxorubicin and cisplatin as in arm I, paclitaxel IV over 3 hours on day 2, and G-CSF SC or pegfilgrastim on days 3-12. Treatment repeats every 3 weeks for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 614 patients (307 per treatment arm) will be accrued for this study within 5.2 years.
Interventions
DRUGDoxorubicin Hydrochloride
Given IV
DRUGCisplatin
Given IV
BIOLOGICALFilgrastim
Given SC
BIOLOGICALPegfilgrastim
Given SC
DRUGPaclitaxel
Given IV
Sponsors
Eastern Cooperative Oncology Group
National Cancer Institute (NCI)
Gynecologic Oncology Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed advanced endometrial carcinoma with any histology, including: * Clear cell and serous papillary carcinoma * Surgical stage III disease, including: * Positive adnexa * Tumor invading the serosa * Positive pelvic and/or paraaortic nodes * Involvement of bowel mucosa * Intraabdominal metastases * Positive pelvic washings * Vaginal involvement within the radiation port * Must have had prior surgery, including hysterectomy and bilateral salpingo-oophorectomy * Tumor maximally debulked to a maximum residual diameter of no greater than 2 cm * Paraaortic lymph node sampling allowed * If positive, must have negative chest CT scan * No recurrent disease * No parenchymal liver metastases * No disease outside the abdomen * Performance status - GOG 0-2 * At least 3 months * Absolute neutrophil count at least 1,500/mm\^3 * Platelet count at least 100,000/mm\^3 * Bilirubin no greater than 1.5 times normal * SGOT/SGPT no greater than 3 times normal * Alkaline phosphatase no greater than 3 times normal * Creatinine no greater than 1.6 mg/dL * LVEF at least 50% within 6 months of study entry * No other prior or concurrent malignancy within the past 5 years except adequately treated nonmelanoma skin cancer * No serious comorbid illness that would preclude study participation * No prior chemotherapy * See Disease Characteristics * No prior pelvic or abdominal radiotherapy * No prior radiotherapy for prior malignancy * See Disease Characteristics
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recurrence-Free Survival of Eligible Patients Who Received a Random Treatment Allocation. | study entry up to 5 years post treatment | Recurrence is defined as discovery of disease not previously present by clinical, radiographic, and/or laboratory means or as a 50% or greater increase in the product of two perpendicular diameters from any documented lesion. Recurrence-free survival is defined as time in months the patient is alive, recurrence-free starting from the date of randomization. Intention to treat among eligible participants who receive random treatment allocation. |
Countries
United States
Participant flow
Recruitment details
All patients were initially registered and initiated radiation treatment. Following succsessful completion of radiation treatment, participants with no evidence of disease received a random treatment allocation.
Participants by arm
| Arm | Count |
|---|---|
| Arm 1 Treatment randomization following RT.
radiation followed by doxorubicin 45 mg/m2 and cisplatin 50 mg/m2 G-CSF 5mcg/kg Days 2-11 | 270 |
| Arm 2 Treatment randomization following RT:
radiation followed by doxorubicin 45 mg/m2 and cisplatin 50 mg/m2 day 1 paclitaxel 3-Hr 160 mg/m2 day 2 G-CSF 5 mcg/kg days 3-12 | 282 |
| Radiation (RT) Only Tumor volume directed pelvic plus or minus para-aortic irradiation (plus or minus brachytherapy) | 64 |
| Total | 616 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 15 | 39 | 5 |
| Overall Study | Death | 0 | 1 | 2 |
| Overall Study | Disease progression | 13 | 6 | 26 |
| Overall Study | Ineligible | 18 | 16 | 9 |
| Overall Study | Other | 4 | 2 | 5 |
| Overall Study | Refused further treatment | 15 | 13 | 26 |
Baseline characteristics
| Characteristic | Arm 1 | Arm 2 | Radiation (RT) Only | Total |
|---|---|---|---|---|
| Age, Continuous | 58.8 years STANDARD_DEVIATION 11.1 | 58.8 years STANDARD_DEVIATION 9.5 | 63.9 years STANDARD_DEVIATION 10.7 | 59.3 years STANDARD_DEVIATION 10.5 |
| Sex: Female, Male Female | 270 Participants | 282 Participants | 64 Participants | 616 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 259 / 261 | 278 / 278 |
| serious Total, serious adverse events | 10 / 261 | 21 / 278 |
Outcome results
Primary
Recurrence-Free Survival of Eligible Patients Who Received a Random Treatment Allocation.
Recurrence is defined as discovery of disease not previously present by clinical, radiographic, and/or laboratory means or as a 50% or greater increase in the product of two perpendicular diameters from any documented lesion. Recurrence-free survival is defined as time in months the patient is alive, recurrence-free starting from the date of randomization. Intention to treat among eligible participants who receive random treatment allocation.
Time frame: study entry up to 5 years post treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1 | Recurrence-Free Survival of Eligible Patients Who Received a Random Treatment Allocation. | Alive, Recurrence-Free | 159 participants |
| Arm 1 | Recurrence-Free Survival of Eligible Patients Who Received a Random Treatment Allocation. | Recurrence or Death | 111 participants |
| Arm 2 | Recurrence-Free Survival of Eligible Patients Who Received a Random Treatment Allocation. | Alive, Recurrence-Free | 175 participants |
| Arm 2 | Recurrence-Free Survival of Eligible Patients Who Received a Random Treatment Allocation. | Recurrence or Death | 107 participants |
Comparison: Primary outcome is measured as a treatment hazard ratio stratified by stage and assuming proportional hazards.~Recurrence-free survival hazard ratio: Arm 2 is relative to Arm 1.95% CI: [0.69, 1.17]