A Randomized Phase III Study of Tumor Volume Directed Pelvic Plus or Minus Para-Aortic Irradiation Followed by Cisplatin and Doxorubicin or Cisplatin, Doxorubicin and Paclitaxel for Advanced Endometrial Carcinoma
Overview
- Phase
- Phase 3
- Intervention
- Doxorubicin Hydrochloride
- Conditions
- Endometrial Adenocarcinoma
- Sponsor
- Gynecologic Oncology Group
- Enrollment
- 659
- Locations
- 1
- Primary Endpoint
- Recurrence-Free Survival of Eligible Patients Who Received a Random Treatment Allocation.
- Status
- Completed
- Last Updated
- 10 years ago
Overview
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.
Investigators
Eligibility Criteria
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
Exclusion Criteria
- Not provided
Arms & Interventions
Arm I (doxorubicin, cisplatin, filgrastim, pegfilgrastim)
Patients receive doxorubicin IV over 30 minutes immediately followed by cisplatin IV over 1 hour on day 1. Patients also receive filgrastim (G-CSF) SC or pegfilgrastim on days 2-11.
Intervention: Doxorubicin Hydrochloride
Arm I (doxorubicin, cisplatin, filgrastim, pegfilgrastim)
Patients receive doxorubicin IV over 30 minutes immediately followed by cisplatin IV over 1 hour on day 1. Patients also receive filgrastim (G-CSF) SC or pegfilgrastim on days 2-11.
Intervention: Cisplatin
Arm I (doxorubicin, cisplatin, filgrastim, pegfilgrastim)
Patients receive doxorubicin IV over 30 minutes immediately followed by cisplatin IV over 1 hour on day 1. Patients also receive filgrastim (G-CSF) SC or pegfilgrastim on days 2-11.
Intervention: Filgrastim
Arm I (doxorubicin, cisplatin, filgrastim, pegfilgrastim)
Patients receive doxorubicin IV over 30 minutes immediately followed by cisplatin IV over 1 hour on day 1. Patients also receive filgrastim (G-CSF) SC or pegfilgrastim on days 2-11.
Intervention: Pegfilgrastim
Arm II (doxorubicin, cisplatin, paclitaxel, filgrastim)
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.
Intervention: Doxorubicin Hydrochloride
Arm II (doxorubicin, cisplatin, paclitaxel, filgrastim)
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.
Intervention: Cisplatin
Arm II (doxorubicin, cisplatin, paclitaxel, filgrastim)
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.
Intervention: Filgrastim
Arm II (doxorubicin, cisplatin, paclitaxel, filgrastim)
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.
Intervention: Pegfilgrastim
Arm II (doxorubicin, cisplatin, paclitaxel, filgrastim)
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.
Intervention: Paclitaxel
Outcomes
Primary Outcomes
Recurrence-Free Survival of Eligible Patients Who Received a Random Treatment Allocation.
Time Frame: 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.