Vaginal Cuff Brachytherapy Followed by Chemotherapy in Endometrial Cancer

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine the feasibility of treatment in patients with high risk endometrial cancer treated by vaginal cuff brachytherapy followed by 3 cycles of dose dense paclitaxel and carboplatin chemotherapy.

Detailed Description
-----------------
Before the patient begins the study: Endometrial cancer is commonly treated with surgery. The patient must have already had surgery including hysterectomy (removal of the uterus) prior to being considered eligible for this study. The surgery may also include removal of pelvic and para-aortic lymph nodes. Following the surgery, the doctor will identify if the patient has factors related to the cancer which places the patient at a greater risk for the cancer returning. Prior to participating in this study there are exams, tests or procedures to find out if the patient can be treated in the study. Most are part of regular cancer care. Treatment: All patients will receive radiation therapy followed by three cycles of dose dense paclitaxel and carboplatin chemotherapy. Radiation therapy will be delivered either by LDR or HDR brachytherapy and must be specified at the time of enrollment. The vaginal brachytherapy should be started within 12 weeks of surgery (within 2 weeks of enrollment). Chemotherapy should start within 3 weeks of initiating brachytherapy. Study participation will be up to two years.

Official Title
-----------------
Phase II Trial of Vaginal Cuff Brachytherapy Followed by Adjuvant Chemotherapy With Carboplatin and Dose Dense Paclitaxel in Patients With High-Risk Endometrial Cancer

Conditions
-----------------
Endometrial Cancer, Papillary Serous, Clear Cell Endometrial Cancer

Intervention / Treatment
-----------------
* Radiation: Vaginal Cuff Brachytherapy
* Drug: Carboplatin
* Drug: Paclitaxel


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: All patients must have undergone hysterectomy. Bilateral salpingooophorectomy is strongly encouraged but not mandatory. Pelvic and para-aortic lymphadenectomy are optional, but strongly encouraged. Peritoneal washing are optional. If either a bilateral salpingo-oophorectomy or nodal dissection was not performed, post-operative pre-treatment CT/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. All patients will be staged according to the FIGO 2009 staging system and 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 ≥18 years with 3 risk factors Risk factors: Grade 2 or 3 tumor, (+) lymphovascular space invasion, outer ½ 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). Patients must have GOG performance status 0, 1, or 2. Patients must have adequate bone marrow, renal, hepatic and neurologic function per protocol. Patients who have met the pre-entry requirements specified in protocol; testing values/results must meet eligibility criteria specified in protocol. Patients must have signed an approved informed consent and authorization permitting release of personal health information. Exclusion Criteria: Patients with recurrent disease. Patients with GOG performance status of 3 or 4. Greater than 12 weeks elapsed from surgery to enrollment. Patients have prior pelvic or abdominal radiation therapy. Known hypersensitivity to any component of study treatment that resulted in drug discontinuation. Significant intercurrent illness including, but not limited to, unstable angina pectoris, and cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements Active pregnancy or lactation. Prior malignancy requiring treatment within the last 3 years.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vaginal Cuff Brachytherapy + Chemotherapy<br>Vaginal cuff brachytherapy followed by Carboplatin (AUC 6) on day 1and Paclitaxel 80 mg/m2 IV over 1 hour days 1, 8, and 15 X 3 total cycles | Radiation: Vaginal Cuff Brachytherapy<br>* Within 12 weeks of surgery. Either LDR or HDR brachytherapy will be permitted<br>Drug: Carboplatin<br>* Carboplatin IV on day 1 of a 21 day cycle for 3 cycles<br>Drug: Paclitaxel<br>* Paclitaxel IV on days 1,8 and 15 of a 21 day cycle for 3 cycles<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients Completing the Protocol | Defined as completion of vaginal cuff brachytherapy followed by 3 cycles of dose dense paclitaxel and carboplatin chemotherapy | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Adverse Events Related to Acute Toxicity During Treatment | Frequency and severity of adverse events as assessed by the CTCAE v4 | 4 months | 
| Sites of Failure | Proportion of participants who recur in regional versus distant recurrence | up to 2 years | 
| Recurrence-free Survival | time from study entry to the first tumor recurrence | up to 2 years | 
| Contributing Cause of Death | The contributing cause of death for patients with high risk endometrial cancer | up to 2 years | 
| Overall Survival | time from study entry to death | up to 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Endometrial Cancer, Gynecologic Cancer, radiation therapy