Pelvic Radiation Therapy or Vaginal Implant Radiation Therapy, Paclitaxel, and Carboplatin in Treating Patients With High-Risk Stage I or Stage II 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)

- The procedures may be performed via laparotomy or laparoscopy (including
robot-assisted) as per the surgeon?s preference; the surgeon must record in the
operative report whether a lymphadenectomy was performed (see link above to
Surgical Procedures Manual) or not; a specific number of lymph nodes removed will
not be utilized for eligibility, but the operative report should reflect that the
procedure performed was consistent with the procedures described in the GOG
Surgical Manual

- 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:

- Age >= 70 years with one risk factor

- Age >= 50 with 2 risk factors

- Age >= 18 years with 3 risk factors

- Risk factors: grade 2 or 3 tumor, (+) lymphovascular space invasion, outer ?
myometrial invasion; patients with these risk criteria may be enrolled with
either positive or negative cytology

- 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

- Note: If serum creatinine > ULN, a 24-hour creatinine clearance must be collected
and must be > 50 mL/min

- 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:

- Patients who have already received non-surgical therapy for endometrial cancer
including chemotherapy, radiation (example, pre-operative or post-operative
brachytherapy), hormonal or biologic therapy

- Patients identified with pathologically confirmed spread of cancer beyond the uterus
and cervix to pelvic or para-aortic lymph nodes, adnexal structures, and/or other
anatomic sites, or patients with serous or clear cell histology and with positive
cytologic washings

- Patients with nodal (for patients who did not have nodal dissection performed) or
distant disease determined based on imaging studies; patients with suspicious nodes
that have been biopsied (re-staging operation, fine needle aspiration [FNA]) and are
pathologically negative will be eligible

- Patients with a history of other invasive malignancies, with the exception of
non-melanoma skin cancer, are excluded if there is any evidence of other malignancy
being present within the last 5 years; patients are excluded if their previous cancer
treatment contraindicates this protocol therapy; specifically, patients who have
received prior radiotherapy directed to treat disease within the abdominal cavity or
pelvis are excluded

- Prior radiation of localized cancer of the breast, head and neck, thyroid, or skin is
permitted, provided that it was completed more than 5 years prior to registration, and
the patient remains free of recurrent or metastatic disease

- Patients may have received prior adjuvant chemotherapy for localized breast cancer,
provided that it was completed more than 5 years prior to registration, and the
patient remains free of recurrent or metastatic disease

- Patients who have contraindications to pelvic radiation therapy (RT) (e.g. pelvic
kidney, connective tissue disease, inflammatory bowel disease, etc.) should be
screened in advance and not be considered eligible for the trial

- Patients with recurrent endometrial cancer

- Patients with surgical or clinical, FIGO 2009 stage III or IV endometrial carcinoma

- Patients with non-epithelial uterine malignancies such as uterine carcinosarcoma or
leiomyosarcoma