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

NCT ID: NCT00411138

Last Updated: 2023-10-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

670 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-11-23

Study Completion Date

2024-12-31

Brief Summary

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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

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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.

Conditions

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Endometrial Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Radiation Therapy

Pelvic Radiotherapy alone

Group Type ACTIVE_COMPARATOR

Radiation Therapy

Intervention Type RADIATION

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

Radiation Therapy and Chemotherapy

Pelvic Radiation plus 2 concurrent cycles cisplatin followed by 4 adjuvant cycles carboplatin and paclitaxel

Group Type EXPERIMENTAL

Radiation Therapy

Intervention Type RADIATION

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

cisplatin

Intervention Type DRUG

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

carboplatin

Intervention Type DRUG

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

Paclitaxel

Intervention Type DRUG

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

Interventions

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Radiation Therapy

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

Intervention Type RADIATION

cisplatin

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

Intervention Type DRUG

carboplatin

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

Intervention Type DRUG

Paclitaxel

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

Intervention Type DRUG

Other Intervention Names

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RT 3D conformal radiotherapy IMRT brachytherapy Cisplatine Carboplatine Carbotaxol Taxol Taxolcarbo

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

90 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Cancer Research UK

OTHER

Sponsor Role collaborator

Australia New Zealand Gynaecological Oncology Group

OTHER

Sponsor Role collaborator

NCIC Clinical Trials Group

NETWORK

Sponsor Role collaborator

Mario Negri Institute for Pharmacological Research

OTHER

Sponsor Role collaborator

UNICANCER

OTHER

Sponsor Role collaborator

Leiden University

OTHER

Sponsor Role lead

Responsible Party

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Carien Creutzberg

Chief Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Carien L. Creutzberg, MD, PhD

Role: STUDY_CHAIR

Leiden University Medical Center

Locations

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Leiden University Medical Center

Leiden, , Netherlands

Site Status

Countries

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Netherlands

References

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Jameson MG, McNamara J, Bailey M, Metcalfe PE, Holloway LC, Foo K, Do V, Mileshkin L, Creutzberg CL, Khaw P. Results of the Australasian (Trans-Tasman Oncology Group) radiotherapy benchmarking exercise in preparation for participation in the PORTEC-3 trial. J Med Imaging Radiat Oncol. 2016 Aug;60(4):554-9. doi: 10.1111/1754-9485.12447. Epub 2016 Apr 5.

Reference Type BACKGROUND
PMID: 27059658 (View on PubMed)

ANZGOG and PORTEC Group; Blinman P, Mileshkin L, Khaw P, Goss G, Johnson C, Capp A, Brooks S, Wain G, Kolodziej I, Veillard AS, O'Connell R, Creutzberg CL, Stockler MR. Patients' and clinicians' preferences for adjuvant chemotherapy in endometrial cancer: an ANZGOG substudy of the PORTEC-3 intergroup randomised trial. Br J Cancer. 2016 Nov 8;115(10):1179-1185. doi: 10.1038/bjc.2016.323. Epub 2016 Oct 20.

Reference Type BACKGROUND
PMID: 27764842 (View on PubMed)

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. Clinical consequences of upfront pathology review in the randomised PORTEC-3 trial for high-risk endometrial cancer. Ann Oncol. 2018 Feb 1;29(2):424-430. doi: 10.1093/annonc/mdx753.

Reference Type RESULT
PMID: 29190319 (View on PubMed)

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. 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. Lancet Oncol. 2016 Aug;17(8):1114-1126. doi: 10.1016/S1470-2045(16)30120-6. Epub 2016 Jul 7.

Reference Type RESULT
PMID: 27397040 (View on PubMed)

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, Jurgenliemk-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. 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. Lancet Oncol. 2018 Mar;19(3):295-309. doi: 10.1016/S1470-2045(18)30079-2. Epub 2018 Feb 12.

Reference Type RESULT
PMID: 29449189 (View on PubMed)

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, Jurgenliemk-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. 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. Lancet Oncol. 2019 Sep;20(9):1273-1285. doi: 10.1016/S1470-2045(19)30395-X. Epub 2019 Jul 22.

Reference Type RESULT
PMID: 31345626 (View on PubMed)

Post CCB, de Boer SM, Powell ME, Mileshkin L, Katsaros D, Bessette P, Haie-Meder C, Ottevanger NPB, Ledermann JA, Khaw P, D'Amico R, Fyles A, Baron MH, Kitchener HC, Nijman HW, Lutgens LCHW, Brooks S, Jurgenliemk-Schulz IM, Feeney A, Goss G, Fossati R, Ghatage P, Leary A, Do V, Lissoni AA, McCormack M, Nout RA, Verhoeven-Adema KW, Smit VTHBM, Putter H, Creutzberg CL. Long-Term Toxicity and Health-Related Quality of Life After Adjuvant Chemoradiation Therapy or Radiation Therapy Alone for High-Risk Endometrial Cancer in the Randomized PORTEC-3 Trial. Int J Radiat Oncol Biol Phys. 2021 Mar 15;109(4):975-986. doi: 10.1016/j.ijrobp.2020.10.030. Epub 2020 Oct 28.

Reference Type RESULT
PMID: 33129910 (View on PubMed)

Leon-Castillo A, de Boer SM, Powell ME, Mileshkin LR, Mackay HJ, Leary A, Nijman HW, Singh N, Pollock PM, Bessette P, Fyles A, Haie-Meder C, Smit VTHBM, Edmondson RJ, Putter H, Kitchener HC, Crosbie EJ, de Bruyn M, Nout RA, Horeweg N, Creutzberg CL, Bosse T; TransPORTEC consortium. Molecular Classification of the PORTEC-3 Trial for High-Risk Endometrial Cancer: Impact on Prognosis and Benefit From Adjuvant Therapy. J Clin Oncol. 2020 Oct 10;38(29):3388-3397. doi: 10.1200/JCO.20.00549. Epub 2020 Aug 4.

Reference Type RESULT
PMID: 32749941 (View on PubMed)

Post CCB, Stelloo E, Smit VTHBM, Ruano D, Tops CM, Vermij L, Rutten TA, Jurgenliemk-Schulz IM, Lutgens LCHW, Jobsen JJ, Nout RA, Crosbie EJ, Powell ME, Mileshkin L, Leary A, Bessette P, Putter H, de Boer SM, Horeweg N, Nielsen M, Wezel TV, Bosse T, Creutzberg CL. Prevalence and Prognosis of Lynch Syndrome and Sporadic Mismatch Repair Deficiency in Endometrial Cancer. J Natl Cancer Inst. 2021 Sep 4;113(9):1212-1220. doi: 10.1093/jnci/djab029.

Reference Type RESULT
PMID: 33693762 (View on PubMed)

Wortman BG, Post CCB, Powell ME, Khaw P, Fyles A, D'Amico R, Haie-Meder C, Jurgenliemk-Schulz IM, McCormack M, Do V, Katsaros D, Bessette P, Baron MH, Nout RA, Whitmarsh K, Mileshkin L, Lutgens LCHW, Kitchener HC, Brooks S, Nijman HW, Astreinidou E, Putter H, Creutzberg CL, de Boer SM. Radiation Therapy Techniques and Treatment-Related Toxicity in the PORTEC-3 Trial: Comparison of 3-Dimensional Conformal Radiation Therapy Versus Intensity-Modulated Radiation Therapy. Int J Radiat Oncol Biol Phys. 2022 Feb 1;112(2):390-399. doi: 10.1016/j.ijrobp.2021.09.042. Epub 2021 Oct 2.

Reference Type RESULT
PMID: 34610387 (View on PubMed)

Khaw P, Do V, Lim K, Cunninghame J, Dixon J, Vassie J, Bailey M, Johnson C, Kahl K, Gordon C, Cook O, Foo K, Fyles A, Powell M, Haie-Meder C, D'Amico R, Bessette P, Mileshkin L, Creutzberg CL, Moore A. Radiotherapy Quality Assurance in the PORTEC-3 (TROG 08.04) Trial. Clin Oncol (R Coll Radiol). 2022 Mar;34(3):198-204. doi: 10.1016/j.clon.2021.11.015. Epub 2021 Dec 11.

Reference Type RESULT
PMID: 34903431 (View on PubMed)

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, Jurgenliemk-Schulz IM, Feeney A, Lutgens LCHW, Bouma J, Leon-Castillo A, Nout RA, Putter H, Bosse T, Creutzberg CL. Adjuvant chemoradiotherapy versus radiotherapy alone in women with high-risk endometrial cancer (PORTEC-3): 10-year clinical outcomes and post-hoc analysis by molecular classification from a randomised phase 3 trial. Lancet Oncol. 2025 Oct;26(10):1370-1381. doi: 10.1016/S1470-2045(25)00379-1. Epub 2025 Sep 5.

Reference Type DERIVED
PMID: 40921169 (View on PubMed)

Related Links

Access external resources that provide additional context or updates about the study.

http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30120-6/fulltext

Publication on Toxicity and Quality of life outcomes of the PORTEC-3 trial

http://www.msbi.nl/portec3

trial website (with protocol and all documents)

Other Identifiers

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CKTO-2006-04

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

ISRCTN14387080

Identifier Type: REGISTRY

Identifier Source: secondary_id

P06.031-PORTEC-3

Identifier Type: OTHER

Identifier Source: secondary_id

2007-004917-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CDR0000521447; P06.031

Identifier Type: -

Identifier Source: org_study_id

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