Short Course Vaginal Cuff Brachytherapy in Treating Participants With Stage I-II Endometrial Cancer

Official title

Short Course Adjuvant Vaginal Cuff Brachytherapy (VCB) in Early Endometrial Cancer Compared to Standard of Care (SAVE)

Overview

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

• Radiation Vaginal Cuff Brachytherapy
  Undergo standard of care vaginal cuff brachytherapy
• Radiation Short course vaginal cuff brachytherapy
  Undergo short course vaginal cuff brachytherapy

Primary outcome measures

• Change in Quality of Life From Baseline to 1 Month [Time frame: At 1 month post treatment]
• Cohort 2: Participant-Reported Financial Toxicity [Time frame: One month after brachytherapy]

Secondary outcome measures (5)

• Treatment-related Symptoms on HRQOL Using European Organization for Research and Treatment of Cancer Endometrial Cancer Module (EORTC EN24), Question 48 [Time frame: one month post-treatment]
• USD Amount Charged for Procedures [Time frame: Approximately 6 months after treatment]
• Cohort 2: Participant-Reported Diet [Time frame: One month after brachytherapy]
• Cohort 2: Participant-Reported Activity Levels [Time frame: One month after brachytherapy]
• Cohort 2: Financial Toxicity Correlated With Quality of Life [Time frame: One month after brachytherapy]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 5 centers

• Stanford Cancer Center — Palo Alto
• Loyola University Medical Center — Maywood
• MD Anderson — Houston
• Huntsman Cancer Institute/University of Utah — Salt Lake City
• Intermountain Medical Center / LDS Hospital — Salt Lake City

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. PMID 19367689
• Briet 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. PMID 15721428
• Cohn 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. PMID 12468320
• Thomas 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. PMID 20975365
• Bosse 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. PMID 26049688
• Lee 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. PMID 16434629
• Kirchheiner 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 PMID 24721589
• Aalders 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. PMID 6999399

Identifiers

NCT: NCT03422198 · HCI103841 · NCI-2018-00011

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗