A Randomized Phase III Trial of Cisplatin and Tumor Volume Directed Irradiation Followed by Carboplatin and Paclitaxel vs. Carboplatin and Paclitaxel for Optimally Debulked, Advanced Endometrial Carcinoma
A Randomized Phase III Trial of Cisplatin and Tumor Volume Directed Irradiation Followed by Carboplatin and Paclitaxel vs. Carboplatin and Paclitaxel for Optimally Debulked, Advanced Endometrial Carcinoma
This randomized phase III trial studies carboplatin and paclitaxel to see how well they work with or without cisplatin and radiation therapy in treating patients with stage I-IVA endometrial cancer. Drugs used in chemotherapy, such as carboplatin, paclitaxel, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving chemotherapy and radiation therapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether carboplatin and paclitaxel are more effective with or without cisplatin and radiation therapy in treating patients with endometrial cancer.
PRIMARY OBJECTIVES:
I. To determine if treatment with cisplatin and volume-directed radiation followed by carboplatin and paclitaxel for 4 cycles (experimental arm) reduces the rate of recurrence or death (i.e., increases recurrence-free survival) when compared to chemotherapy consisting of carboplatin and paclitaxel for 6 cycles (control arm) in patients with stages III-IVA endometrial carcinoma (< 2 cm residual disease) or patients with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage I or II serous (uterine papillary serous carcinoma [UPSC]) or clear cell endometrial carcinoma and positive cytology.
SECONDARY OBJECTIVES:
I. To determine if treatment with cisplatin and volume-directed radiation followed by carboplatin and paclitaxel for 4 cycles (experimental arm) reduces the rate of death (i.e., increases survival) when compared to chemotherapy consisting of carboplatin and paclitaxel for 6 cycles (control arm) in patients with stages III-IVA endometrial carcinoma (< 2 cm residual disease) or patients with FIGO 2009 stage I or II serous (UPSC) or clear cell endometrial carcinoma and positive cytology.
II. To compare the regimens with respect to acute and late adverse effects of therapy.
III. To determine the impact of patient-reported quality of life during and following treatment for up to 1 year with the two treatment regimens.
TERTIARY OBJECTIVES:
I. To bank formalin-fixed, paraffin-embedded (FFPE) tumor tissue and whole blood specimens for future research.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive cisplatin intravenously (IV) on days 1 and 29. Patients also undergo radiation therapy once daily (QD), 5 days a week, for 5-6 weeks. Some patients may then undergo brachytherapy over 2-3 weeks. Beginning within 8 weeks after completion of chemoradiotherapy, patients receive paclitaxel IV over 3 hours and carboplatin IV on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive paclitaxel IV over 3 hours and carboplatin IV on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
Inclusion Criteria:
All patients with surgical stage III or IVA endometrial carcinoma per FIGO 2009 staging criteria including clear cell and serous papillary and undifferentiated carcinoma
Patients with FIGO 2009 surgical stage I or II endometrial clear cell or serous carcinoma and with positive peritoneal cytology
Surgery must have included a hysterectomy and bilateral salpingo-oophorectomy; pelvic lymph node sampling and para-aortic lymph node sampling are optional
Patients with a Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2
White blood cell (WBC) >= 3,000/mcl
Absolute neutrophil count (ANC) >= 1,500/mcl
Platelet count >= 100,000/mcl
Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) =< 2.5 x upper limit of normal (ULN)
Alkaline phosphatase =< 2.5 times ULN
Bilirubin =< 1.5 times ULN
Creatinine =< institutional ULN
Patients who have met the pre-entry requirements; testing values/results must meet eligibility criteria
Patients who have signed an approved informed consent and authorization permitting release of personal health information
Entry into the study is limited to no more than 8 weeks from the date of surgery
Exclusion Criteria:
Burbank, California 91505, United States
Cameron Park, California 95682, United States
Roseville, California 95661, United States
Sacramento, California 95817, United States
Sylmar, California 91342, United States
Vacaville, California 95687, United States
Miami, Florida 33136, United States
Pekin, Illinois 61554, United States
Louisville, Kentucky 40202, United States
Baltimore, Maryland 21237, United States
Brownstown, Michigan 48183, United States
Saint Louis Park, Minnesota 55416, United States
Las Vegas, Nevada 89109, United States
Las Vegas, Nevada 89113, United States
Las Vegas, Nevada 89149, United States
Scranton, Pennsylvania 18508, United States
American Fork, Utah 84003, United States
Spokane, Washington 99204, United States
Sturgeon Bay, Wisconsin 54235-1495, United States
Summit, Wisconsin 53066, United States
Montreal, Quebec H3H 2R9, Canada
Dalseo-gu, Daegu 42601, South Korea