Endometrial Clear Cell AdenocarcinomaPhase 3SAVENCT03422198
Short Course Vaginal Cuff Brachytherapy in Treating Participants With Stage I-II Endometrial Cancer
A Phase 3 study testing Vaginal Cuff Brachytherapy and Short course vaginal cuff brachytherapy in people with Endometrial Clear Cell Adenocarcinoma and Endometrial Endometrioid Adenocarcinoma, run by University of Utah at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Endometrial Clear Cell Adenocarcinoma, Endometrial Endometrioid Adenocarcinoma, Endometrial Serous Adenocarcinoma
- What is being tested?
- Vaginal Cuff Brachytherapy and Short course vaginal cuff brachytherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 188 participants
- Where
- 5 sitesUnited States
- Study dates
- 2 Feb 2018to 31 Oct 2029
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- Stages of endometrial carcinoma other than described.
- Previous pelvic radiotherapy.
- Concurrent malignancy requiring non-protocol anti-cancer treatment other than surgery.
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
United States5 sites, 3 recruiting
- Recruiting
MD Anderson
Houston, Texas, 77030
Mathew G Geena, 713-792-4594, geenag@mdanderson.org
Anuja Jhingran, MD
- Recruiting
Loyola University Medical Center
Maywood, Illinois, 60153
Carly Quick, RN, 708-327-3255, Carly.quick@luhs.org
Lorena Leon, 464-220-9395, lleon4@luc.edu
- Completed
Stanford Cancer Center
Palo Alto, California, 94304
- Recruiting
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112
Rachel Kingsford, 801-585-0115, rachel.kingsford@hci.utah.edu
Cristina DeCesaris, MD
- Completed
Intermountain Medical Center / LDS Hospital
Salt Lake City, Utah, 84143
About this study
Official title: Short Course Adjuvant Vaginal Cuff Brachytherapy (VCB) in Early Endometrial Cancer Compared to Standard of Care (SAVE)
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.
Read the 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.
- Conditions
- Endometrial Clear Cell Adenocarcinoma, Endometrial Endometrioid Adenocarcinoma, Endometrial Serous Adenocarcinoma, Stage I Uterine Corpus Cancer, Stage IA Uterine Corpus Cancer, Stage IB Uterine Corpus Cancer
- Being tested
- Vaginal Cuff Brachytherapy, Short course vaginal cuff brachytherapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vaginal Cuff BrachytherapyRadiation
Also called best practice, standard of care, standard therapy
Undergo standard of care vaginal cuff brachytherapy
Short course vaginal cuff brachytherapyRadiation
Also called BRACHYTHERAPY, internal radiation, Internal Radiation Brachytherapy, Internal Radiation Therapy
Undergo short course vaginal cuff brachytherapy
| Study group | Role | What they receive |
|---|---|---|
| Short course vaginal cuff brachytherapy | Experimental | Participants undergo short course vaginal cuff brachytherapy for 2 fractions with 1 week apart. Receives: Radiation: Short course vaginal cuff brachytherapy |
| Vaginal cuff brachytherapy | Active comparator | Participants undergo standard of care vaginal cuff brachytherapy for 3-5 fractions over no more than 3 weeks. Receives: Radiation: Vaginal Cuff Brachytherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: At 1 month post treatment
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.
Measured: One month after brachytherapy
Secondary outcomes (5)
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.
Measured: one month post-treatment
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.
Measured: Approximately 6 months after treatment
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.
Measured: One month after brachytherapy
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.
Measured: One month after brachytherapy
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.
Measured: One month after brachytherapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2018
- Study start2 Feb 2018
- Primary completion30 Nov 2026 (estimated)
- Study completion31 Oct 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (34)Papers the sponsor has linked to this study.
- Other trials for Endometrial Clear Cell AdenocarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 188 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Collaborators
- Huntsman Cancer Institute
- Responsible party
- Sponsor
- Investigators
- Cristina DeCesaris, MD, Principal investigator, Huntsman Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03422198
- Sponsor's protocol ID
- HCI103841
- Other IDs
- NCI-2018-00011
- Acronym
- SAVE
- Status last verified
- Sep 2025
- First submitted
- 16 Jan 2018
- Last updated
- 12 Dec 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Pecorelli S. Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynaecol Obstet. 2009 May;105(2):103-4. doi: 10.1016/j.ijgo.2009.02.012. No abstract available.
PubMed 19367689Briet JM, Hollema H, Reesink N, Aalders JG, Mourits MJ, ten Hoor KA, Pras E, Boezen HM, van der Zee AG, Nijman HW. Lymphvascular space involvement: an independent prognostic factor in endometrial cancer. Gynecol Oncol. 2005 Mar;96(3):799-804. doi: 10.1016/j.ygyno.2004.11.033.
PubMed 15721428Cohn DE, Horowitz NS, Mutch DG, Kim SM, Manolitsas T, Fowler JM. Should the presence of lymphvascular space involvement be used to assign patients to adjuvant therapy following hysterectomy for unstaged endometrial cancer? Gynecol Oncol. 2002 Dec;87(3):243-6. doi: 10.1006/gyno.2002.6825.
PubMed 12468320Thomas GM. A role for adjuvant radiation in clinically early carcinoma of the endometrium? Int J Gynecol Cancer. 2010 Oct;20(11 Suppl 2):S64-6. doi: 10.1111/IGC.0b013e3181f5c688.
PubMed 20975365Bosse T, Peters EE, Creutzberg CL, Jurgenliemk-Schulz IM, Jobsen JJ, Mens JW, Lutgens LC, van der Steen-Banasik EM, Smit VT, Nout RA. Substantial lymph-vascular space invasion (LVSI) is a significant risk factor for recurrence in endometrial cancer--A pooled analysis of PORTEC 1 and 2 trials. Eur J Cancer. 2015 Sep;51(13):1742-50. doi: 10.1016/j.ejca.2015.05.015. Epub 2015 Jun 3.
PubMed 26049688Lee CM, Szabo A, Shrieve DC, Macdonald OK, Gaffney DK. Frequency and effect of adjuvant radiation therapy among women with stage I endometrial adenocarcinoma. JAMA. 2006 Jan 25;295(4):389-97. doi: 10.1001/jama.295.4.389.
PubMed 16434629Kirchheiner K, Czajka-Pepl A, Ponocny-Seliger E, Scharbert G, Wetzel L, Nout RA, Sturdza A, Dimopoulos JC, Dorr W, Potter R. Posttraumatic stress disorder after high-dose-rate brachytherapy for cervical cancer with 2 fractions in 1 application under spinal/epidural anesthesia: incidence and risk factors. Int J Radiat Oncol Biol Phys. 2014 Jun 1;89(2):260-7. doi: 10.1016/j.ijrobp.2014.02.018. Epub 2014 Apr 7.
PubMed 24721589Aalders J, Abeler V, Kolstad P, Onsrud M. Postoperative external irradiation and prognostic parameters in stage I endometrial carcinoma: clinical and histopathologic study of 540 patients. Obstet Gynecol. 1980 Oct;56(4):419-27.
PubMed 6999399Creutzberg CL, van Putten WL, Koper PC, Lybeert ML, Jobsen JJ, Warlam-Rodenhuis CC, De Winter KA, Lutgens LC, van den Bergh AC, van de Steen-Banasik E, Beerman H, van Lent M. Surgery and postoperative radiotherapy versus surgery alone for patients with stage-1 endometrial carcinoma: multicentre randomised trial. PORTEC Study Group. Post Operative Radiation Therapy in Endometrial Carcinoma. Lancet. 2000 Apr 22;355(9213):1404-11. doi: 10.1016/s0140-6736(00)02139-5.
PubMed 10791524Keys HM, Roberts JA, Brunetto VL, Zaino RJ, Spirtos NM, Bloss JD, Pearlman A, Maiman MA, Bell JG; Gynecologic Oncology Group. A phase III trial of surgery with or without adjunctive external pelvic radiation therapy in intermediate risk endometrial adenocarcinoma: a Gynecologic Oncology Group study. Gynecol Oncol. 2004 Mar;92(3):744-51. doi: 10.1016/j.ygyno.2003.11.048.
PubMed 14984936ASTEC/EN.5 Study Group; Blake P, Swart AM, Orton J, Kitchener H, Whelan T, Lukka H, Eisenhauer E, Bacon M, Tu D, Parmar MK, Amos C, Murray C, Qian W. Adjuvant external beam radiotherapy in the treatment of endometrial cancer (MRC ASTEC and NCIC CTG EN.5 randomised trials): pooled trial results, systematic review, and meta-analysis. Lancet. 2009 Jan 10;373(9658):137-46. doi: 10.1016/S0140-6736(08)61767-5. Epub 2008 Dec 16.
PubMed 19070891Nout RA, Smit VT, Putter H, Jurgenliemk-Schulz IM, Jobsen JJ, Lutgens LC, van der Steen-Banasik EM, Mens JW, Slot A, Kroese MC, van Bunningen BN, Ansink AC, van Putten WL, Creutzberg CL; PORTEC Study Group. Vaginal brachytherapy versus pelvic external beam radiotherapy for patients with endometrial cancer of high-intermediate risk (PORTEC-2): an open-label, non-inferiority, randomised trial. Lancet. 2010 Mar 6;375(9717):816-23. doi: 10.1016/S0140-6736(09)62163-2.
PubMed 20206777Nout RA, Putter H, Jurgenliemk-Schulz IM, Jobsen JJ, Lutgens LC, van der Steen-Banasik EM, Mens JW, Slot A, Stenfert Kroese MC, van Bunningen BN, Smit VT, Nijman HW, van den Tol PP, Creutzberg CL. Quality of life after pelvic radiotherapy or vaginal brachytherapy for endometrial cancer: first results of the randomized PORTEC-2 trial. J Clin Oncol. 2009 Jul 20;27(21):3547-56. doi: 10.1200/JCO.2008.20.2424. Epub 2009 Jun 22.
PubMed 19546404Sorbe B, Straumits A, Karlsson L. Intravaginal high-dose-rate brachytherapy for stage I endometrial cancer: a randomized study of two dose-per-fraction levels. Int J Radiat Oncol Biol Phys. 2005 Aug 1;62(5):1385-9. doi: 10.1016/j.ijrobp.2004.12.079.
PubMed 16029797McMeekin DS, The University of Oklahoma OC, OK, United States, Filiaci VL, et al. 1A randomized phase III trial of pelvic radiation therapy (PXRT) versus vaginal cuff brachytherapy followed by paclitaxel/carboplatin chemotherapy (VCB/C) in patients with high risk (HR), early stage endometrial cancer (EC): A Gynecologic Oncology Group trial. Gynecol Oncol. 2014;134: 438.