Vaginal Cuff Brachytherapy Fractionation Study

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to see the effects of two different standard of care treatments of endometrial cancer on sexual dysfunction. This study will compare two standard of care treatments: HDR (high dose radiation) vaginal brachytherapy 3 fractions of 7 Gy to HDR vaginal brachytherapy 6 fractions of 4Gy for early stage endometrial cancer.

Detailed Description
-----------------
Patients are randomized to HDR vaginal brachytherapy 7 Gy in 3 fractions prescribed at 5mm. Radiation delivered 4-12 weeks after surgery OR HDR vaginal brachytherapy 4Gy in 6 fractions prescribed at the cylinder surface. Patients have the option to request to decline their randomization and switch to the alternate treatment ARM if they prefer. Radiation delivered 4-12 weeks after surgery. Participants in all Arms will receive standard vaginal dilator for use after treatment (to promote healing). 3 month, 1 year and 2 year follow up assessments are performed.

Official Title
-----------------
A Randomized Phase III Trial of Two Standard Dose Fractionation Regimes for Adjuvant Vaginal Brachytherapy in Early Stage Endometrial Cancer

Conditions
-----------------
Endometrial Cancer

Intervention / Treatment
-----------------
* Radiation: HDR vaginal brachytherapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Willingness and ability to provide written informed consent and to comply with the study protocol as judged by the investigator. Surgery consisted of Total Abdominal or Laparoscopic Hysterectomy and Bilateral Salpingo Oophorectomy (TH-BSO) with or without lymph node dissection. Subject must have FIGO Stage I-II (grade 1-3) pathologically proven (histologic) endometrioid cancer, including all subtypes. Serous, clear cell, and carcinosarcoma histologic pathologies are allowed. Subjects must have no measurable disease after surgery. ECOG Performance Status of 0-2 Age ≥ 18 years Subject must have a life expectancy ≥ 12 months Exclusion Criteria: Disease of more advanced stage (FIGO stage III-IV) or disease for which adjuvant external beam radiation therapy or chemotherapy is indicated Patients with a history of prior pelvic radiation therapy or if additional pelvic radiation therapy is planned Subjects who have not recovered from side effects of agents administered more than 4 weeks prior to the on-study date Subjects that require > 14 weeks between surgery and initiation of radiation therapy on study unless the subject is receiving chemotherapy. Subjects receiving chemotherapy may have radiation therapy initiated within 6 months after surgery. * Subjects who do not meet this criteria may still be eligible. The UVA Coordinating Center and Overall Study PI will review each case and inform the site of the approval decision. Subjects who are receiving any investigational agents or have had any investigational agent within the 30 days prior to the on-study date Subject is unable or unwilling to participate in a study-related procedure Pregnant and breastfeeding women are excluded from this study Subject is a prisoner A serious uncontrolled medical disorder that in the opinion of the Investigator would impair the ability of the subject to receive protocol therapy. Subjects with a history of evidence upon physical examination of central nervous system disease including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of cerebrovascular accident (stroke), transient ischemic attack, or subarachnoid hemorrhage within six months of study entry

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

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This study will compare two standard of care treatments: HDR vaginal brachytherapy 3 fractions of 7Gy to HDR vaginal brachytherapy 6 fractions of 4Gy for early stage endometrial cancer.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ARM A: 3 treatments of 7Gy<br>Arm A: accepted randomization to HDR vaginal brachytherapy in 3 treatments (fractions) of 7Gy for a total dose of 21gy | Radiation: HDR vaginal brachytherapy<br>* HDR vaginal brachytherapy 7 Gy in 3 fractions or HDR vaginal brachytherapy 4 Gy in 6 fractions<br>|
| Active Comparator: ARM B: 6 treatment of 4Gy<br>Arm B: accepted randomization to HDR vaginal brachytherapy 6 treatments (fractions) of 4Gy for a total does of 24gy | Radiation: HDR vaginal brachytherapy<br>* HDR vaginal brachytherapy 7 Gy in 3 fractions or HDR vaginal brachytherapy 4 Gy in 6 fractions<br>|
| Active Comparator: ARM AB: 6 treatment of 4Gy<br>Arm AB: initially randomized to ARM A but wanted to switch to ARM B treatment of HDR vaginal brachytherapy 6 treatments (fractions) of 4Gy for a total does of 24gy | Radiation: HDR vaginal brachytherapy<br>* HDR vaginal brachytherapy 7 Gy in 3 fractions or HDR vaginal brachytherapy 4 Gy in 6 fractions<br>|
| Active Comparator: ARM BA: 3 treatments of 7Gy<br>initially randomized to ARM B but wanted to switch to ARM A of HDR vaginal brachytherapy in 3 treatments (fractions) of 7Gy for a total dose of 21gy | Radiation: HDR vaginal brachytherapy<br>* HDR vaginal brachytherapy 7 Gy in 3 fractions or HDR vaginal brachytherapy 4 Gy in 6 fractions<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Female Sexual Function Index (FSFI) | Using the FSFI, compare patient reported sexual dysfunction at 1 year after completion of treatment | 1 year | 
| Preference Option Randomized Design (PORD) | Assessing the comparative effectiveness of receiving HDR vaginal brachytherapy on Arm B or Arm A for early stage endometrial cancer. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vaginal Length Measurement | Using vaginal dilator compare patient vaginal measurement 1 year after completion of treatment | 1 year | 
| Vaginal Length Measurement | Using vaginal dilator compare patient vaginal measurement 2 years after completion of treatment | 2 years |