Stereotactic Pelvic Adjuvant Radiation Therapy in Cancers of the Uterus II

Study Overview
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Brief Summary
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Adjuvant radiotherapy (RT) plays an important role in reducing the risks of local recurrence after surgery in uterine cancers. Standard adjuvant pelvic radiation treatment targets the pelvic lymph nodes, the post-operative bed, and the upper vagina and is typically treated with intensity modulated radiation therapy (IMRT) which has been shown to improve patient reported gastrointestinal (GI) and genitourinary (GU) toxicities. Although pelvic radiation has been shown to be effective at decreasing locoregional recurrences, patient quality of life and experience can be significantly impacted as pelvic RT comprises of daily radiation for 25 daily treatments, which can be a substantial burden on patients with this disease. Hypofractionated radiotherapy to a dose of 30 Gy in 5 fractions (6 Gy given every other day) for adjuvant radiation treatment in uterine cancer is hypothesized to result in similar rates of acute gastrointestinal toxicities as conventional fractionated radiation.

Official Title
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Stereotactic Pelvic Adjuvant Radiation Therapy in Cancers of the Uterus II: A Phase II Randomized Controlled Trial

Conditions
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Endometrial Cancer

Intervention / Treatment
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* Radiation: Conventional Fractionation
* Radiation: Hypofractionation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with histologically confirmed endometrial adenocarcinoma, serous or clear cell carcinoma. Patient is a candidate for adjuvant pelvic radiation for uterine cancer (+/- vault brachytherapy), meeting one of the following conditions: High grade histology (including serous and clear cell) OR Outer-half myometrial invasion and International Federation of Gynecology and Obstetrics (FIGO) grade 1-2 OR FIGO stage II - III. Patients who are to receive adjuvant systemic therapy sequentially in addition to pelvic radiotherapy will be eligible. Age ≥18 years. Patient is willing and able to give informed consent to participate in this clinical trial. Exclusion Criteria: Patient has had prior pelvic radiotherapy. Patient has a contraindication to pelvic radiotherapy, such as but not limited to a connective tissue disease or inflammatory bowel disease. Patient planned for concurrent chemoradiation therapy.

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Conventional Fractionation Pelvic Radiation<br>Patients randomized to the conventional fractionation arm will be treated with intensity-modulated or volumetric arc therapy technique as per standard protocol. | Radiation: Conventional Fractionation<br>* Dose prescribed is 45 Gy in 25 fractions (1.8 Gy per fraction) delivered daily over 5 weeks.<br>|
| Experimental: Stereotactic Hypofractionated Radiation<br>Patients randomized to hypofractionation will be treated the stereotactic hypofractionated technique. | Radiation: Hypofractionation<br>* Dose prescribed is 30 Gy in 5 fractions (6 Gy per fraction) delivered every other day over 11 days. There will be a minimum of 36 hours and maximum of 96 hours between fractions. The entire course of treatment should be completed within no less than 10 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute bowel toxicity | To compare the acute bowel toxicities associated with hypofractionated vs conventional adjuvant pelvic radiation as measured by the The Expanded Prostate Cancer Index Composite (EPIC) questionnaire. | Baseline to 2 years following RT completion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute bowel toxicities | To compare the acute bowel toxicities associated with hypofractionated treatment and conventional fractionation in adjuvant pelvic radiation for endometrial cancers using the Common Terminology Criteria for Adverse Events (CTCAE v5.0) criteria. | Baseline to 2 years following RT completion | 
| Acute urinary toxicities through CTCAE | To compare the acute urinary toxicities associated with hypofractionated treatment and conventional fractionation in adjuvant pelvic radiation for endometrial cancers using the Common Terminology Criteria for Adverse Events (CTCAE v5.0) criteria. | Baseline to 2 years following RT completion | 
| Acute urinary toxicities through EPIC | To compare the acute urinary toxicities associated with hypofractionated treatment and conventional fractionation in adjuvant pelvic radiation for uterine cancer as measured by EPIC. | Baseline to 2 years following RT completion | 
| Local- regional failure | To compare presence of tumour through physical exam or radiologic imaging between hypofractionated treatment and conventional fractionation. | Baseline to 2 years following RT completion | 
| Disease-free survival | To compare disease-free survival of hypofractionated treatment and conventional fractionation | Baseline to 2 years following RT completion | 
| Quality of life using EORTC QLQ-30 and endometrial module (EN-24) | To compare the effect of hypofractionated treatment and conventional fractionation on quality of life using the using EORTC (European Organisation for Research and Treatment of Cancer) core questionnaire (QLQ-C30) with EN-24 companion. | Baseline to 2 years following RT completion | 
| Correlation of GU toxicity, EORTC, and EPIC | To measure correlations between GU toxicity and EORTC questionnaire versus GU toxicity and EPIC questionnaire. | Baseline to 2 years following RT completion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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endometrial cancer, uterine cancer