Endometrial Clear Cell Adenocarcinoma, Endometrial Endometrioid Adenocarcinoma, Endometrial Serous Adenocarcinoma, Stage IA Uterine Corpus Cancer, Stage IB Uterine Corpus Cancer, Stage II Uterine Corpus Cancer, Stage I Uterine Corpus Cancer, Uterine Corpus Carcinosarcoma, Uterine Corpus Sarcoma
Conditions
Brief summary
This randomized phase III trial studies short course vaginal cuff brachytherapy to see how well it works compared with standard of care vaginal cuff brachytherapy in treating participants with stage I-II endometrial cancer. Short course vaginal cuff brachytherapy, also known as internal radiation therapy, uses (over a shorter period) radioactive material placed directly into or near a tumor in the upper portion of the vagina to kill tumor cells. After completion of cohort 1 (108 participants), the protocol was expended to add a second cohort of 80 additional participants, and re-opened study recruitment.
Detailed description
Endometrial cancer is the most common gynecologic cancer in the Western world and primarily affects postmenopausal women. The primary form of treatment is surgery, consisting of a total abdominal or laparoscopic hysterectomy and bilateral salpingo-oophorectomy. Adjuvant radiotherapy for endometrial cancer has been studied in prospective trials for at least four decades. All trials have demonstrated an improvement in local regional control. However, improvement in survival has not been observed in prospective randomized trials in early-stage patients. There is great heterogeneity in prognoses in stage I patients. National Comprehensive Cancer Network (NCCN) guidelines consequently recommend no treatment in general for low-stage patients, adjuvant brachytherapy for patients with intermediate- and high-intermediate-risk disease, and for patients with deeply invasive tumors with high-grade lesions, external beam radiotherapy is an option (NCCN Guidelines 2016). Over the ensuing decades, there has been a shift toward increasing use of vaginal cuff brachytherapy. This is a phase III, unblinded, randomized trial comparing an experimental arm and a control arm of vaginal cuff brachytherapy: The experimental arm will treat subjects with 2 fractions of vaginal brachytherapy. The control arm will treat subjects with standard-of-care vaginal cuff brachytherapy of 3-5 fractions. Patients will be randomized 1:1 to the different treatment arms. After completion of cohort 1 (108 participants), the protocol was expanded to add a second cohort of 80 additional participants, and reopened study recruitment. Cohort 1 evaluated the non-inferiority of patient Health Related Quality of Life (HRQOL) in the experimental arm compared to the control arm using the Global Health Status from the EORTC QLQ-C30. Cohort 2 will evaluate the frequency and severity of patient-reported financial toxicity in patients with early-stage endometrial cancer treated with vaginal cuff-brachytherapy (VCB) at one month post-VCB.
Interventions
RADIATIONVaginal Cuff Brachytherapy
Undergo standard of care vaginal cuff brachytherapy
RADIATIONShort course vaginal cuff brachytherapy
Undergo short course vaginal cuff brachytherapy
Sponsors
Huntsman Cancer Institute
University of Utah
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed endometrial carcinoma: endometrioid type, serous, and clear cell, to include tumors originating in the cervix, but are primarily located in the uterus, and for whom vaginal cuff brachytherapy is indicated. Carcinosarcoma and other sarcomas are permitted; Federation of Gynecology and Obstetrics (FIGO) stage I and stage II, with one of the following combinations of stage and grade: * Stage IA, grade 1 with LVSI, 2, 3 * Stage IB, grades 1-3 * Stage II, grades 1-3 * Stage IIIA, grades 1-3, not receiving EBRT as part of adjuvant therapy. * Participants post-hysterectomy and free from residual disease. * World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG)-performance status 0-2. * Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines. * Life expectancy of \>2 years.
Exclusion criteria
* Stages of endometrial carcinoma other than described. * Previous pelvic radiotherapy. * Concurrent malignancy requiring non-protocol anti-cancer treatment other than surgery.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Quality of Life From Baseline to 1 Month | At 1 month post treatment | The European Organisation for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-30 (QLQ-30) is used to evaluate quality of life in cancer patients. The questionnaire was given before and one month following treatment. The quality of life score ranges from 0-100, with higher scores indicating better quality of life. Baseline scores can be found in the Baseline Characteristics module. This outcome reports the average change from baseline to Month 1. |
| Cohort 2: Participant-Reported Financial Toxicity | One month after brachytherapy | One month post-brachytherapy, participants will be given the Functional Assessment of Chronic Illness Therapy (FACIT) - COmprehensive Score for financial Toxicity (COST) (FACIT-COST) questionnaire. The score range is 0-44, with higher scores indicating better financial well-being. Mean scores will be reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| USD Amount Charged for Procedures | Approximately 6 months after treatment | The amount charged to participants or their insurance in US Dollars (USD) was collected to evaluate cost of experimental versus standard of care courses of treatment. Data was collected at approximately six months after treatment. |
| Cohort 2: Participant-Reported Activity Levels | One month after brachytherapy | Participants will be asked to complete the NCI Activities Completed over Time in 24-hours (ACT24) questionnaire through the NCI website. Additional information about the questionnaire, methods, and measurements will be updated when results are reported for this outcome. |
| Cohort 2: Financial Toxicity Correlated With Quality of Life | One month after brachytherapy | Mean scores from the FACIT-COST (from Outcome Measure 2: Participant-Reported Financial Toxicity) will be correlated with mean QoL scores (from Outcome Measure 1). Additional information about the methods and measurements will be updated when results are reported for this outcome. |
| Cohort 2: Participant-Reported Diet | One month after brachytherapy | Participants will be asked to complete the National Cancer Institute (NCI) Diet History Questionnaire 3 (DHQIII) through the NCI website. Additional information about the questionnaire, methods, and measurements will be updated when results are reported for this outcome. |
| Treatment-related Symptoms on HRQOL Using European Organization for Research and Treatment of Cancer Endometrial Cancer Module (EORTC EN24), Question 48 | one month post-treatment | The European Organisation for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Endometrial-24 (QLQ-EN24) was used to evaluate quality of life in cancer patients with endometrial cancers. The questionnaire was given before and one month following treatment. From this assessment, one question was selected as an indicator for this outcome, which measured whether participants felt less feminine as a result of their disease or treatment. The score ranges from 0-100, with higher scores indicating feeling less feminine. Baseline scores can be found in the Baseline Characteristics module. This outcome reports the average change from baseline to Month 1. |
Countries
United States
Contacts
Primary ContactRachel Kingsford
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Experimental: Short Course Vaginal Cuff Brachytherapy Participants undergo short course vaginal cuff brachytherapy for 2 fractions with 1 week apart. | 54 |
| Control: Standard of Care Vaginal Cuff Brachytherapy Participants undergo standard of care vaginal cuff brachytherapy for 3-5 fractions over no more than 3 weeks. | 54 |
| Total | 108 |
Baseline characteristics
| Characteristic | Experimental: Short Course Vaginal Cuff Brachytherapy | Total | Control: Standard of Care Vaginal Cuff Brachytherapy |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 32 Participants | 55 Participants | 23 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants | 53 Participants | 31 Participants |
| Age, Continuous | 66.5 years | 65 years | 63.65 years STANDARD_DEVIATION 9.68 |
| Baseline EORTC Quality of Life Score | 72.28 score on a scale STANDARD_DEVIATION 21.5 | 70.17 score on a scale STANDARD_DEVIATION 21.26 | 67.88 score on a scale STANDARD_DEVIATION 21.74 |
| Baseline EORTC Symptom Score | 10.46 score on a scale STANDARD_DEVIATION 26.24 | 13.47 score on a scale STANDARD_DEVIATION 27.32 | 16.67 score on a scale STANDARD_DEVIATION 28.35 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 11 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 46 Participants | 94 Participants | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 10 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants | 9 Participants | 2 Participants |
| Race (NIH/OMB) White | 41 Participants | 86 Participants | 45 Participants |
| Sex: Female, Male Female | 54 Participants | 108 Participants | 54 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 54 | 1 / 54 |
| other Total, other adverse events | 46 / 54 | 50 / 54 |
| serious Total, serious adverse events | 2 / 54 | 2 / 54 |
Outcome results
Primary
Change in Quality of Life From Baseline to 1 Month
The European Organisation for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-30 (QLQ-30) is used to evaluate quality of life in cancer patients. The questionnaire was given before and one month following treatment. The quality of life score ranges from 0-100, with higher scores indicating better quality of life. Baseline scores can be found in the Baseline Characteristics module. This outcome reports the average change from baseline to Month 1.
Time frame: At 1 month post treatment
Population: Five control arm participants were excluded from analysis because they did not complete the Month 1 questionnaire. One control arm participant was excluded because they did not complete the baseline questionnaire. Two experimental arm participants were excluded from analysis because they did not complete the Month 1 questionnaire.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental: Short Course Vaginal Cuff Brachytherapy | Change in Quality of Life From Baseline to 1 Month | 2.08 score on a scale | Standard Deviation 15.02 |
| Control: Standard of Care Vaginal Cuff Brachytherapy | Change in Quality of Life From Baseline to 1 Month | 2.08 score on a scale | Standard Deviation 18.23 |
Primary
Cohort 2: Participant-Reported Financial Toxicity
One month post-brachytherapy, participants will be given the Functional Assessment of Chronic Illness Therapy (FACIT) - COmprehensive Score for financial Toxicity (COST) (FACIT-COST) questionnaire. The score range is 0-44, with higher scores indicating better financial well-being. Mean scores will be reported.
Time frame: One month after brachytherapy
Secondary
Cohort 2: Financial Toxicity Correlated With Quality of Life
Mean scores from the FACIT-COST (from Outcome Measure 2: Participant-Reported Financial Toxicity) will be correlated with mean QoL scores (from Outcome Measure 1). Additional information about the methods and measurements will be updated when results are reported for this outcome.
Time frame: One month after brachytherapy
Secondary
Cohort 2: Participant-Reported Activity Levels
Participants will be asked to complete the NCI Activities Completed over Time in 24-hours (ACT24) questionnaire through the NCI website. Additional information about the questionnaire, methods, and measurements will be updated when results are reported for this outcome.
Time frame: One month after brachytherapy
Secondary
Cohort 2: Participant-Reported Diet
Participants will be asked to complete the National Cancer Institute (NCI) Diet History Questionnaire 3 (DHQIII) through the NCI website. Additional information about the questionnaire, methods, and measurements will be updated when results are reported for this outcome.
Time frame: One month after brachytherapy
Secondary
Treatment-related Symptoms on HRQOL Using European Organization for Research and Treatment of Cancer Endometrial Cancer Module (EORTC EN24), Question 48
The European Organisation for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Endometrial-24 (QLQ-EN24) was used to evaluate quality of life in cancer patients with endometrial cancers. The questionnaire was given before and one month following treatment. From this assessment, one question was selected as an indicator for this outcome, which measured whether participants felt less feminine as a result of their disease or treatment. The score ranges from 0-100, with higher scores indicating feeling less feminine. Baseline scores can be found in the Baseline Characteristics module. This outcome reports the average change from baseline to Month 1.
Time frame: one month post-treatment
Population: Five control arm participants were excluded from analysis because they did not complete the Month 1 questionnaire. One control arm participants was excluded because they did not complete the baseline questionnaire. Three experimental arm participants were excluded from analysis because they did not complete the Month 1 questionnaire.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental: Short Course Vaginal Cuff Brachytherapy | Treatment-related Symptoms on HRQOL Using European Organization for Research and Treatment of Cancer Endometrial Cancer Module (EORTC EN24), Question 48 | 0.65 score on a scale | Standard Deviation 22.6 |
| Control: Standard of Care Vaginal Cuff Brachytherapy | Treatment-related Symptoms on HRQOL Using European Organization for Research and Treatment of Cancer Endometrial Cancer Module (EORTC EN24), Question 48 | -6.25 score on a scale | Standard Deviation 29.7 |
Secondary
USD Amount Charged for Procedures
The amount charged to participants or their insurance in US Dollars (USD) was collected to evaluate cost of experimental versus standard of care courses of treatment. Data was collected at approximately six months after treatment.
Time frame: Approximately 6 months after treatment
Population: Amount charged for procedures could not be obtained for six participants on the experimental arm.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental: Short Course Vaginal Cuff Brachytherapy | USD Amount Charged for Procedures | 33204.97 US Dollars (USD) | Standard Deviation 16867.76 |
| Control: Standard of Care Vaginal Cuff Brachytherapy | USD Amount Charged for Procedures | 45919.55 US Dollars (USD) | Standard Deviation 19808.48 |