Randomized Trial of Radiation Therapy With or Without Chemotherapy for Endometrial Cancer

Conditions

Endometrial Cancer

Keywords

endometrial clear cell carcinoma, stage II endometrial carcinoma, stage IA grade 3 endometrial carcinoma, stage IB endometrial carcinoma, stage IIIA endometrial carcinoma, stage IIIB endometrial carcinoma, stage IIIC endometrial carcinoma

Brief summary

RATIONALE: Drugs used in chemotherapy, such as cisplatin, paclitaxel, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving chemotherapy and radiation therapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether giving chemotherapy together with radiation therapy is more effective than giving radiation therapy alone in treating endometrial cancer. PURPOSE: This randomized phase III trial is studying chemotherapy and radiation therapy to see how well they work compared with radiation therapy alone in treating patients with high-risk, stage I, stage II, or stage III endometrial cancer.

Detailed description

OBJECTIVES: Primary * Compare the overall survival and failure-free survival of patients with high-risk stage IB-III endometrial carcinoma treated with concurrent chemoradiotherapy followed by adjuvant chemotherapy vs pelvic radiotherapy alone. Secondary * Compare the rates of pelvic and distant recurrence, severe (grades 3 and 4) treatment-related toxicity, and quality of life of patients treated with these regimens. OUTLINE: This is a multicenter, prospective, open-label, randomized, controlled study. Patients are stratified according to participating group (DGOG vs UK NCRI vs NCIC CTG vs MaNGO vs Unicancer), type of surgery (total abdominal hysterectomy and bilateral salpingo-oophorectomy \[TAH-BSO\] vs TAH-BSO plus lymphadenectomy vs laparoscopic hysterectomy \[TLH-BSO\] vs TLH-BSO plus lymphadenectomy), stage (IA vs IB vs II vs III), and histological type (endometrioid carcinoma vs serous or clear cell carcinoma). Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients receive external-beam pelvic radiotherapy 5 days a week for up to 6 weeks, combined with cisplatin IV days 1 and 22. Patients with cervical involvement undergo vaginal brachytherapy boost. At least 3 weeks after completion of chemoradiotherapy, patients undergo adjuvant chemotherapy comprising paclitaxel IV and carboplatin IV on day 1. Adjuvant chemotherapy repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. * Arm II: Patients undergo external-beam pelvic radiotherapy (and vaginal brachytherapy alone in case of cervical involvement) as in arm I. Quality of life is assessed at baseline, completion of radiotherapy, completion of chemotherapy, at 6 months, and then once a year for 5 years. After completion of study therapy, patients are followed periodically for up to 10 years. PROJECTED ACCRUAL: A total of 670 patients will be accrued for this study.

Post CCB, de Boer SM, Powell ME, Mileshkin L, Katsaros D, Bessette P, Leary A, Ottevanger PB, McCormack M, Khaw P, D'Amico R, Fyles A, Chargari C, Kitchener HC, Do V, Lissoni A, Provencher D, Genestie C, Nijman HW, Whitmarsh K, Jürgenliemk-Schulz IM, Feeney A, Lutgens LCHW, Bouma J, Leon-Castillo A, Nout RA, Putter H, Bosse T, Creutzberg CL.

2025-09-051 citations

10.1016/s1470-2045(25)00379-1

PR024/#394 Molecular profiling of P53 mutant endometrial cancer reveals distinct subgroups with opportunities for personalized therapeutic approaches

Félix Blanc‐Durand, Claire J.H. Kramer, Etienne Rouleau, Antoine Vasseur, Tjalling Bosse et al. (20 authors)

2023-11-01

10.1136/ijgc-2023-igcs.66

Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): patterns of recurrence and post-hoc survival analysis of a randomised phase 3 trial.

de Boer SM, Powell ME, Mileshkin L, Katsaros D, Bessette P, Haie-Meder C, Ottevanger PB, Ledermann JA, Khaw P, D'Amico R, Fyles A, Baron MH, Jürgenliemk-Schulz IM, Kitchener HC, Nijman HW, Wilson G, Brooks S, Gribaudo S, Provencher D, Hanzen C, Kruitwagen RF, Smit VTHBM, Singh N, Do V, Lissoni A, Nout RA, Feeney A, Verhoeven-Adema KW, Putter H, Creutzberg CL, PORTEC Study Group.

2019-07-22303 citations

10.1016/s1470-2045(19)30395-x

Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an international, open-label, multicentre, randomised, phase 3 trial.

de Boer SM, Powell ME, Mileshkin L, Katsaros D, Bessette P, Haie-Meder C, Ottevanger PB, Ledermann JA, Khaw P, Colombo A, Fyles A, Baron MH, Jürgenliemk-Schulz IM, Kitchener HC, Nijman HW, Wilson G, Brooks S, Carinelli S, Provencher D, Hanzen C, Lutgens LCHW, Smit VTHBM, Singh N, Do V, D'Amico R, Nout RA, Feeney A, Verhoeven-Adema KW, Putter H, Creutzberg CL, PORTEC study group.

2018-02-12407 citations

10.1016/s1470-2045(18)30079-2

Clinical consequences of upfront pathology review in the randomised PORTEC-3 trial for high-risk endometrial cancer.

de Boer SM, Wortman BG, Bosse T, Powell ME, Singh N, Hollema H, Wilson G, Chowdhury MN, Mileshkin L, Pyman J, Katsaros D, Carinelli S, Fyles A, McLachlin CM, Haie-Meder C, Duvillard P, Nout RA, Verhoeven-Adema KW, Putter H, Creutzberg CL, Smit VTHBM, for PORTEC Study Group.

2018-02-0163 citations

10.1093/annonc/mdx753

Final results of the international randomized PORTEC-3 trial of adjuvant chemotherapy and radiation therapy (RT) versus RT alone for women with high-risk endometrial cancer.

Stephanie M. de Boer, Melanie Powell, Linda Mileshkin, Dionyssios Katsaros, Paul Bessette et al. (21 authors)

Journal of Clinical Oncology2017-05-2033 citations

10.1200/jco.2017.35.15_suppl.5502

Toxicity and quality of life after adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): an open-label, multicentre, randomised, phase 3 trial.

de Boer SM, Powell ME, Mileshkin L, Katsaros D, Bessette P, Haie-Meder C, Ottevanger PB, Ledermann JA, Khaw P, Colombo A, Fyles A, Baron MH, Kitchener HC, Nijman HW, Kruitwagen RF, Nout RA, Verhoeven-Adema KW, Smit VT, Putter H, Creutzberg CL, PORTEC study group.

2016-07-07115 citations

10.1016/s1470-2045(16)30120-6

Adjuvant chemotherapy and radiation therapy (RT) versus RT alone for women with high-risk endometrial cancer: Toxicity and quality-of-life results of the randomized PORTEC-3 trial.

Carien L. Creutzberg, Stephanie M. de Boer, Hein Putter, Melanie Powell, Linda Mileshkin et al. (20 authors)

Journal of Clinical Oncology2015-05-203 citations

10.1200/jco.2015.33.15_suppl.5501

Interventions

RADIATIONRadiation Therapy

External beam pelvic radiotherapy (48.6 Gy in 1.8 Gy fractions) Vaginal brachytherapy boost in case of cervical involvement

DRUGcisplatin

cisplatin 50 mg/m2 i.v., 2 cycles during radiotherapy, 3 wks interval

DRUGcarboplatin

carboplatin AUC 5, 4 cycles after completion of radiotherapy, 3 wks interval

DRUGPaclitaxel

paclitaxel 175 mg/m2, 4 cycles after completion of radiotherapy, 3 wks interval

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

FEMALE

Age

18 Years to 90 Years

Healthy volunteers

No

Inclusion criteria

* Histologically confirmed endometrial carcinoma, with one of the following postoperative FIGO 2009 stages and grade: 1. stage IA with invasion, grade 3 with documented LVSI 2. stage IB grade 3 3. stage II 4. stage IIIA or IIIC; or IIIB if parametrial invasion only 5. stage IA (with invasion), IB, II, or III with serous or clear cell histology * WHO-performance status 0-2 * WBC ≥ 3.0 x 109/L. * Platelets ≥ 100 x 109/L. * Bilirubin ≤ 1.5 x UNL * ASAT/ALAT ≤ 2.5 x UNL * Written informed consent

Exclusion criteria

* Uterine sarcoma (including carcinosarcoma) * Previous malignancy (except for non-melanomatous skin cancer) \< 10 yrs * Previous pelvic radiotherapy * Hormonal therapy or chemotherapy for this tumor * Macroscopic stage II for which Wertheim type hysterectomy (eligible if stage II grade 3 or stage III at pathology) * Prior diagnosis of Crohn's disease or ulcerative colitis * Residual macroscopic tumor after surgery * Creatinine clearance ≤ 60 ml/min (Cockroft) or ≤ 50 ml/min (EDTA clearance, or measured creatinine clearance) * Impaired cardiac function, prohibiting the infusion of large amounts of fluid during cisplatin therapy * Peripheral Neuropathy \> or = grade 2 * Hearing impairment \> or = grade 3, or born deaf

Design outcomes

Primary

Measure	Time frame	Description
Overall survival	5 years	co-primary endpoint
Failure-free survival	5 years	co-primary endpoint

Secondary

Measure	Time frame	Description
Quality of life by QLQ-C30 v3.0	5 years	Health-related overall quality of life and patient-reported symptom measures
Severe treatment-related morbidity	5 years	Acute serious events and SAE and late grade 3-4 complications
Vaginal or pelvic relapse	5 years	Both vaginal or pelvic relapse as first failure and total vaginal or pelvic relapse
Distant metastases	5 years	Both distant relapse as first failure and total distant relapse

Countries

Netherlands

Outcome results

None listed