Study of Pelvic Hypofractionated Radiotherapy in Endometrial Cancer

Study Overview
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Brief Summary
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This study will investigate if a shorter treatment course (known as hypofractionation) for pelvic radiation is safe for women with endometrial cancer. Doctors leading the study will also determine the safest and most tolerable dose of shortened radiation (hypofractionation) used to treat women in this study. Because this study will shorten the radiation course typically used to treat endometrial cancer, each daily treatment given to women in this study will be slightly higher than normal to ensure that the total radiation dose they receive is still effective and similar to the radiation dose they would receive if they were not participating in this study (standard treatment).

Official Title
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Phase I Safety Study of Whole Pelvic Hypofractionated Radiotherapy in Women With Endometrial Cancer

Conditions
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Endometrial Cancer

Intervention / Treatment
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* Radiation: Hypofractionated Radiation
* Other: Clinical Follow-Up and Assessments


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of endometrial cancer with any of the following primary histologic types: endometrioid, papillary serous, clear cell, carcinosarcoma, or mixed epithelial histologies. Age ≥ 18 years. Must have been diagnosed with Stage I-III disease according to The International Federation of Gynecology and Obstetrics (FIGO). Must have been treated with definitive intent, including standard-of-care hysterectomy, without any gross residual disease post-operatively. Nodal dissection is not required, but if it is not performed, then diagnostic imaging to confirm absence of gross pelvic or para-aortic disease should be obtained pre- or post-operatively. Recommended to undergo whole pelvic radiotherapy without concurrent chemotherapy or para-aortic radiation. Chemotherapy before or after radiotherapy is acceptable. Exclusion Criteria: Distant metastases as determined clinically or radiographically based upon standard-of-care work-up for endometrial cancer. Concurrent (or other) chemotherapy occurring at the time of study. Gross residual disease (cancer cells that remain after attempts to remove the cancer have been made) post-operatively and/or at the time of radiation based upon pre-op or post-op imaging, intra-operative findings, and gynecologic oncologists' judgment. History of small bowel obstruction, inflammatory bowel disease, irritable bowel syndrome, connective tissue disorder requiring ongoing active medical management, or prior radiation therapy directed to the pelvis. Unresolved chemotherapy-associated diarrhea or abdominopelvic pain requiring medication prior to the initiation of radiation. Recommendation to undergo para-aortic nodal irradiation.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hypofractionated Radiation Treatment (Dose-Finding Arm)<br>All study participants in this arm will receive hypofractionated whole pelvic radiation treatment for a shortened time period of 3-5 weeks. The goal of this arm is to establish a safe and tolerable dose of shortened (hypofractionated) pelvic radiation treatment for study participants. Once a safe and tolerable dose is established for this shortened form of radiation treatment, participants who meet criteria for the second phase of this study will participate in an expansion cohort that will explore the efficacy (how effective shortened/hypofractionated radiation treatment is for treating endometrial cancer). | Radiation: Hypofractionated Radiation<br>* Radiation treatment in which the total dose of radiation is divided into large doses and treatments are given less often. Hypofractionated radiation therapy is given over a shorter period of time (fewer days or weeks) than standard radiation therapy.<br>|
| Experimental: Expansion Cohort (Efficacy Arm)<br>Participants in this arm will test how effective hypofractionated/shortened whole radiation treatment is (efficacy) at the dose established in the first phase of this study by following up with their doctors to report their current health status and symptoms during clinical visits. Participants will return for routine clinical follow-up approximately 1 month following radiation, then at 3 months following radiation, then every 3 months for the next 2 years following treatment. | Other: Clinical Follow-Up and Assessments<br>* At each visit, the subject will be evaluated for any signs of their endometrial cancer or symptoms returning (clinical disease recurrence) and any negative side effects associated with their prior radiation treatment. Study participants will also be asked to fill out a survey regarding bowel/urinary habits and quality of life questionnaires (known as the EPIC questionnaire) during these visits. The data collected during these clinical follow up visits will be used to determine how effective hypofractionated/shortened whole radiation therapy is for treating endometrial cancer.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Maximum Tolerated Dose of Hypofractionated Whole Pelvic Radiation Treatment | The maximum tolerated dose-per-fraction regimen of whole pelvic radiation therapy that will be administered during uterine cancer treatment. | 3-5 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity Determined by Reported Adverse Events for Hypofractionated Whole Pelvic Radiation Treatment | The acute toxicity profile of hypofractionated radiation therapy using CTCAE v5.0. CTCAE GU toxicity will be determined using the domains of urinary frequency, urinary incontinence, and urinary urgency (whichever is maximum). Time point of evaluation is on the last day of radiation. | 3-5 weeks. | 
| Rate of Pelvic Control 2 Years Post Radiation | The rate of pelvic control at 2 years post-radiation using CTCAE v5.0 domains of diarrhea and proctitis (whichever is maximum). Study participants will follow for routine clinical follow-up approximately 1 month following radiation, then at 3 months following radiation, then every 3 months for the next 2 years following treatment. Each follow-up time period will be evaluated for CTCAE GI and GU maximum toxicity. Crude rates and cumulative incidence of pelvic failure will be calculated. Pelvic failure is defined as clinical or radiographic evidence of recurrent disease within the irradiated pelvis (pelvic lymph nodes, vaginal cuff, or parametria) as determined by the treating physician(s). Peritoneal metastases will not be considered a pelvic failure. | 2 years after last dose of radiation treatment. |