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

Endometrial Cancer Clinical Trial

— PORTEC-3  

Official title:

Randomized Phase III Trial Comparing Concurrent Chemoradiation and Adjuvant Chemotherapy With Pelvic Radiation Alone in High Risk and Advanced Stage Endometrial Carcinoma: PORTEC-3

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00411138
• Other study ID #: CDR0000521447; P06.031
• Secondary ID: CKTO-2006-04ISRC
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: November 23, 2006
• Est. completion date: December 31, 2024

Study information

• Verified date: October 2023
• Source: Leiden University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 670
• Est. completion date: December 31, 2024
• Est. primary completion date: November 29, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Endometrial Cancer
• Endometrial Neoplasms

Intervention

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

Drug:
• cisplatin
cisplatin 50 mg/m2 i.v., 2 cycles during radiotherapy, 3 wks interval
• carboplatin
carboplatin AUC 5, 4 cycles after completion of radiotherapy, 3 wks interval
• Paclitaxel
paclitaxel 175 mg/m2, 4 cycles after completion of radiotherapy, 3 wks interval

Locations

Country	Name	City	State
Netherlands	Leiden University Medical Center	Leiden

Sponsors (6)

Lead Sponsor	Collaborator
Leiden University	Australia New Zealand Gynaecological Oncology Group, Cancer Research UK, Mario Negri Institute for Pharmacological Research, NCIC Clinical Trials Group, UNICANCER

Country where clinical trial is conducted

Netherlands, 

References & Publications (11)

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. — View Citation

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 L — View Citation

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 stud — View Citation

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 — View Citation

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 — View Citation

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. — View Citation

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 — View Citation

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 — View Citation

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, Gh — View Citation

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, Creutz — View Citation

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, Putte — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

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

External Links

•   trial website (with protocol and all documents)