Clinical trial NCT00376844: External-Beam Radiation Therapy Compared With Vaginal Brachytherapy After Surgery for Stage I Endometrial Cancer
Official title: PORTEC-2, Postoperative Radiation Therapy for Endometrial Carcinoma - A Multicenter Randomised Phase III Trial Comparing External Beam Radiation and Vaginal Brachytherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Endometrial Cancer
Keywords: stage I endometrial carcinoma
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
Collaborators: name: Dutch Cancer Society
First posted: 2006-09-15
Enrollment: 427
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Exterbal beam radiation therapy versus vaginal brachytherapy
Primary purpose: TREATMENT

Brief summary: RATIONALE: External-beam radiation therapy uses high-energy x-rays to kill tumor cells. Implant radiation therapy uses radioactive material placed directly into or near a tumor to kill tumor cells. Giving external-beam radiation therapy or implant radiation therapy after surgery may kill any tumor cells that remain after surgery. Sometimes, after surgery, the tumor may not need more treatment until it progresses. In this case, observation may be sufficient. It is not yet known whether radiation therapy is more effective than observation when given after surgery in treating stage I endometrial cancer.

PURPOSE: This randomized phase III trial is studying external-beam radiation therapy or implant radiation therapy to see how well they work compared with observation in treating patients who have undergone surgery for stage I endometrial cancer.

Detailed description: OBJECTIVES:

* Compare the rate of 5-year locoregional relapse in patients undergoing external-beam radiotherapy or vaginal brachytherapy vs observation only after surgery for stage I endometrial cancer.
* Compare 5-year rate of distant metastases in these patients.
* Determine overall survival rate in these patients.
* Determine prognostic factors for relapse and morbidity.

OUTLINE: This is a randomized, multicenter study. Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients undergo either vaginal brachytherapy or external-beam radiotherapy.
* Arm II: Patients are observed and undergo no further treatment. After completion of study treatment, patients are followed for approximately 83 days.

PROJECTED ACCRUAL: A total of 400 patients will be accrued for this study.

Eligibility criteria: INCLUSION CRITERIA:

* Diagnosis of FIGO 1988 stage I-IIA endometrial cancer, meeting 1 of the following criteria:

  * Age ≥60, stage IC grade 1 or 2 with deep (≥ 50%) myometrial invasion
  * Age ≥60, stage IB grade 2 or 3 (with \< 50% myometrial invasion)
  * Stage IIA, any age
* No grade 3 endometrial carcinoma with deep myometrial invasion
* Total abdominal hysterectomy and bilateral salpingo-oophorectomy required prior to randomisation
* WHO performance status 0-2

EXCLUSION CRITERIA:

* Serous or clear cell histology or uterine sarcoma
* staging lymphadenectomy
* interval between surgery and radiotherapy \> 8 weeks
* history of previous malignant disease (except basal cell carcinoma of skin)
* previous radiotherapy, hormonal therapy or chemotherapy
* diagnosis of Chrohn's disease or ulcerative colitis

Primary outcomes:
measure: Vaginal relapse
timeFrame: 5 years
Secondary outcomes:
measure: Rate of distant metastases
timeFrame: 5 years
measure: Overall survival
timeFrame: 5 years
measure: Adverse effects
timeFrame: 5 years
measure: Health-related quality of life
timeFrame: 5 years
measure: Pelvic relapse
timeFrame: 5 years
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
Study officials:
affiliation: Leiden University Medical Center
name: Carien L. Creutzberg, MD, PhD
role: STUDY_CHAIR
References:
citation: McCloskey SA, Tchabo NE, Malhotra HK, Odunsi K, Rodabaugh K, Singhal P, Lele S, Jaggernauth W. Adjuvant vaginal brachytherapy alone for high risk localized endometrial cancer as defined by the three major randomized trials of adjuvant pelvic radiation. Gynecol Oncol. 2010 Mar;116(3):404-7. doi: 10.1016/j.ygyno.2009.06.027. Epub 2009 Nov 27.
citation: Nout RA, Putter H, Jurgenliemk-Schulz IM, Jobsen JJ, Lutgens LC, van der Steen-Banasik EM, Mens JW, Slot A, Stenfert Kroese MC, Nijman HW, van de Poll-Franse LV, Creutzberg CL. Five-year quality of life of endometrial cancer patients treated in the randomised Post Operative Radiation Therapy in Endometrial Cancer (PORTEC-2) trial and comparison with norm data. Eur J Cancer. 2012 Jul;48(11):1638-48. doi: 10.1016/j.ejca.2011.11.014. Epub 2011 Dec 14.
citation: Nout 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.
citation: Nout RA, Putter H, Jürgenliemk-Schulz IM, et al.: Vaginal brachytherapy versus external beam pelvic radiotherapy for high-intermediate risk endometrial cancer: Results of the randomized PORTEC-2 trial. [Abstract] J Clin Oncol 26 (Suppl 15): A-LBA5503, 2008.
citation: Nout 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.
citation: de Boer SM, Nout RA, Jurgenliemk-Schulz IM, Jobsen JJ, Lutgens LC, van der Steen-Banasik EM, Mens JW, Slot A, Stenfert Kroese MC, Oerlemans S, Putter H, Verhoeven-Adema KW, Nijman HW, Creutzberg CL. Long-Term Impact of Endometrial Cancer Diagnosis and Treatment on Health-Related Quality of Life and Cancer Survivorship: Results From the Randomized PORTEC-2 Trial. Int J Radiat Oncol Biol Phys. 2015 Nov 15;93(4):797-809. doi: 10.1016/j.ijrobp.2015.08.023. Epub 2015 Aug 18.