A Phase III Trial of Pelvic Radiation Therapy Versus Vaginal Cuff Brachytherapy Followed by Paclitaxel/Carboplatin Chemotherapy in Patients With High Risk, Early Stage Endometrial Carcinoma
A Phase III Trial of Pelvic Radiation Therapy Versus Vaginal Cuff Brachytherapy Followed by Paclitaxel/Carboplatin Chemotherapy in Patients With High Risk, Early Stage Endometrial Carcinoma
This randomized phase III trial studies pelvic radiation therapy to see how well it works compared with vaginal implant radiation therapy, paclitaxel, and carboplatin in treating patients with high-risk stage I or stage II endometrial cancer. Radiation therapy uses high-energy x-rays to kill tumor cells. Implant radiation therapy uses radioactive material placed directly into or near a tumor to kill tumor cells. Drugs used in chemotherapy, such as paclitaxel and carboplatin, 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. It is not yet known whether pelvic radiation therapy alone is more effective than vaginal implant radiation therapy, paclitaxel, and carboplatin in treating patients with endometrial cancer.
PRIMARY OBJECTIVES:
I. To determine if treatment with vaginal cuff brachytherapy followed by three cycles of chemotherapy reduces the rate of recurrence or death (i.e. increases recurrence-free survival) when compared to pelvic radiation therapy.
SECONDARY OBJECTIVES:
I. To compare survival between the two treatment groups. II. To compare patterns of failure between the two treatment groups. III. To compare physical functioning, fatigue and neurotoxicity between the two treatment groups.
IV. To examine associations between primary comorbid illnesses and obesity on survival, fatigue and physical functioning.
V. To evaluate the psychometric properties (such as construct validity, reliability, sensitivity to treatment and responsiveness over time) of the Patient-Reported-Outcomes Measurement Information System (PROMIS) Fatigue Short form 1, and to evaluate fatigue measurement equivalence between women with endometrial cancer and age-matched women from the general United States (US) population.
TERTIARY OBJECTIVES:
I. To evaluate the ability of gene expression signatures in early stage endometrial cancer to predict recurrence and to explore the association between gene expression signatures in early stage endometrial cancer and clinical characteristics and outcome.
II. To bank whole blood specimens for future research.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients undergo conventional or intensity-modulated pelvic radiation therapy once daily, 5 days a week, for 5-6 weeks (total of 25-28 fractions) in the absence of disease progression or unacceptable toxicity. Patients with stage II disease or stage I disease with a confirmed diagnosis of clear cell and/or papillary serous histology may also undergo 1 or 2 intravaginal (i.e., vaginal cuff) brachytherapy boost treatments.
ARM II: Patients undergo vaginal cuff brachytherapy comprising 3-5 high-dose rate brachytherapy treatments over approximately 2 weeks or 1 or 2 low-dose rate brachytherapy treatments over 1-2 days. Beginning within 3 weeks after initiating brachytherapy, patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 30-60 minutes on day 1. Chemotherapy repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter for up to 5 years.
Inclusion Criteria:
To be considered eligible to participate in this trial, all patients must have undergone hysterectomy; bilateral salpingo-oophorectomy (open or laparoscopic approach) is strongly encouraged
Peritoneal cytology should be obtained on entering the peritoneal cavity, as described in the Gynecologic Oncology Group (GOG) Surgical Procedures Manual (https://gogmember.gog.org/manuals/pdf/surgman.pdf); pelvic and para-aortic lymphadenectomy are optional, but strongly encouraged (as staged patients enrolled on GOG-0210-molecular markers in endometrial carcinoma are eligible for this study)
If either a bilateral salpingo-oophorectomy or nodal dissection was not performed, post-operative pre-treatment computed tomography (CT)/magnetic resonance imaging (MRI) is required and must not demonstrate evidence suggestive of metastatic disease (adnexa, nodes, intraperitoneal disease); post-operative, pre-treatment CT/MRI must be performed if a pelvic and para-aortic nodal dissection was not performed
For the purposes of description, patients will be staged according to the International Federation of Gynecology and Obstetrics (FIGO) 2009 staging system; eligibility is defined based on clinical-pathologic features; patients with endometrial carcinoma (endometrioid types) confined to the corpus uteri or with endocervical glandular involvement fitting one of the following high-intermediate risk factor categories:
Patients with stage II endometrial carcinoma (any histology) with cervical stromal invasion (occult or gross involvement), with or without high-intermediate risk factors
Patients with serous or clear cell histology (with or without other high-intermediate risk factors) are eligible provided the disease is uterine-confined (with or without cervical stromal invasion or endocervical glandular involvement), and with peritoneal cytology negative for malignancy
Patients must have GOG performance status 0, 1, or 2
Absolute neutrophil count (ANC) >= 1,500/mcl (equivalent to Common Toxicity Criteria [CTCAE version [v] 3.0] grade 1)
Platelets >= 100,000/mcl (CTCAE v3.0 grade 0-1)
Serum creatinine =< institutional upper limit normal (ULN), CTCAE v 3.0 grade 0
Bilirubin =< 1.5 x ULN (CTCAE v3.0 grade 1)
Serum glutamic oxaloacetic transaminase (SGOT) =< 2.5 x ULN (CTCAE grade 0-1)
Alkaline phosphatase =< 2.5 x ULN (CTCAE grade 0-1)
Neuropathy (sensory and motor) =< CTCAE v3.0 grade 1
Patients who have met the pre-entry requirements; testing values/results must meet eligibility criteria
Patients must have signed an approved informed consent and authorization permitting release of personal health information
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
Orlando, Florida 32806, United States
Louisville, Kentucky 40202, United States
Shreveport, Louisiana 71103, United States
Baltimore, Maryland 21237, United States
Saint Louis Park, Minnesota 55416, United States
New Brunswick, New Jersey 08903, United States
New York, New York 10032, United States
Wilmington, North Carolina 28401, United States
Winston-Salem, North Carolina 27104, United States
Spartanburg, South Carolina 29307, United States
Yakima, Washington 98902, United States
Summit, Wisconsin 53066, United States
Jung-gu, Incheon 400-711, South Korea