|- candidate number||11049|
|- NTR Number||NTR3263|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||29-jan-2012|
|- Secondary IDs||UL2011-5336 / P11.185; KWF / METC LUMC|
|- Public Title||PORTEC-4: Randomised trial investigating the role and optimal dose of vaginal brachytherapy for endometrial cancer.|
|- Scientific Title||PORTEC-4: Randomised Phase III Trial Comparing Vaginal Brachytherapy (two doses schedules: 21 or 15 Gy HDR in 3 fractions) and Observation after Surgery in patients with Endometrial Carcinoma with High-Intermediate Risk Features.|
|- hypothesis||Although vaginal brachytherapy reduces vaginal recurrence compared to observation after surgery for endometrial cancers with high-intermediate risk features, ultimate 5-year vaginal control including treatment for relapse will be similar, and a lower dose of vaginal brachytherapy (15 Gy vs 21 Gy in 3 fractions) has similar efficiacy with reduced vaginal side effects.|
|- Healt Condition(s) or Problem(s) studied||Endometrial carcinoma, Radiotherapy, Risk factors, Vaginal brachytherapy, Adjuvant treatment|
|- Inclusion criteria||1. Histologically confirmed endometrioid type endometrial carcinoma, FIGO 2009 stage I, with one of the following combinations of substage, age, and grade:|
A. Stage IA, age 60 years or older and grade 3;
B. Stage IB, age 60 years or older and grade 1 or 2;
C. Stage IB, any age, grade 1-2 with documented lymph-vascular space invasion (LVSI).
2. Surgery consisted of Total Abdominal or Laparoscopic Hysterectomy and Bilateral Salpingo-oophorectomy (TH-BSO);
3. WHO-performance status 0-2;
4. Written informed consent.
|- Exclusion criteria||1. Any other stage and type of endometrial carcinoma;|
2. Histological types papillary serous carcinoma or clear cell carcinoma;
3. Uterine sarcoma (including carcinosarcoma);
4. Previous malignancy (except for non-melanomatous skin cancer) < 5 yrs;
5. Previous pelvic radiotherapy;
6. Interval between the operation and start of radiotherapy exceeding 8 weeks.
|- mec approval received||yes|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-mei-2012|
|- planned closingdate||1-mei-2017|
|- Target number of participants||500|
|- Interventions||Patients are randomised (2:1) to receive vaginal brachytherapy (standard arm), or observation after surgery (experimental arm); patients in the vaginal brachytherapy group are randomized 1:1 to standard dose (21 Gy in 3 Gy fractions), or reduced dose (15 Gy in 3 fractions). |
|- Primary outcome||Primary endpoint: Vaginal recurrence;|
Second primary endpoint: 5-year vaginal control including treatment for relapse.
|- Secondary outcome||1. Vaginal toxicity;|
2. Quality of life;
3. Pelvic recurrence;
4. Overall survival.
|- Timepoints||5-year rates of recurrence, vaginal control, survival, quality of life, vaginal toxicity.|
Evaluation at 6-months invervals.
|- Trial web site||www.msbi.nl/portec4|
|- CONTACT FOR PUBLIC QUERIES||Dr. C.L. Creutzberg|
|- CONTACT for SCIENTIFIC QUERIES||Dr. C.L. Creutzberg|
|- Sponsor/Initiator ||Leiden University Medical Center (LUMC)|
(Source(s) of Monetary or Material Support)
|Dutch Cancer Society|
|- Publications||PORTEC-1 trial: Creutzberg CL et al, Lancet 355:1404-1411, 2000|
PORTEC-2 trial: Nout RA et al, Lancet 375:816-823, 2010
Quality of life: Nout RA et al, J Clin Oncol 27:3547-3556, 2009
|- Brief summary||Background: |
Endometrial cancer (EC) is the most common gynaecological cancer. Surgery (hysterectomy and oophorectomy) is the primary treatment. Previous randomized trials, among which the PORTEC-1 trial, have shown that postoperative radiation therapy (RT) significantly reduces the risk of vaginal and pelvic recurrence from 14 to 4%, but without difference in overall survival. Most (75%) local recurrences are located in the proximal vagina, and can effectively be treated with RT at the time of recurrence. After completion of the PORTEC-1 trial, the indication for RT has become limited to patients with risk factors. The PORTEC-2 trial has shown that for these patients, vaginal brachytherapy alone is highly effective in preventing vaginal recurrence, with less side effects and better quality of life than external beam pelvic radiotherapy. However, treating all patients with risk factors with brachytherapy is still significant overtreatment. If a watchful waiting policy would be adopted, with prompt treatment in case of vaginal relapse, the eventual local control (including treatment for relapse) might be very similar to the local control after adjuvant brachytherapy. A range of published brachytherapy dose schedules has equal efficacy, and the rate of vaginal atrophy changes in PORTEC-2 suggests that the standard dose schedule of 21 Gy in 3 fractions of 7 Gy could be compared to a lower dose schedule.
Objectives and Design:
In this multicenter trial, 500 patients with endometrioid type endometrial adenocarcinoma with high-intermediate risk features will be randomised (2:1) to vaginal brachytherapy (standard arm) and observation (experimental arm). Patients in the vaginal brachytherapy arm will be 1:1 randomized to brachytherapy dose 21 Gy HDR in 3 fractions of 7 Gy each (standard dose) and brachytherapy dose 15 Gy HDR at 5 mm depth, in 3 fractions of 5 Gy (lower dose). Primary study endpoint is vaginal relapse; second primary endpoint is 5-year vaginal control including treatment for vaginal relapse. Secondary objectives are pelvic recurrence; overall survival; vaginal toxicity; and quality of life. Patients will be followed closely and prospectively evaluated for outcome, vaginal symptoms and quality of life.
|- Main changes (audit trail)||Trial closed due to extensive changes in design, new modified trial registered under number NTR5841 -28-jun-2016|
|- RECORD||29-jan-2012 - 1-jul-2016|