Clinical trial NCT00411138: Randomized Trial of Radiation Therapy With or Without Chemotherapy for Endometrial Cancer
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
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
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
Collaborators: name: Cancer Research UK
name: Australia New Zealand Gynaecological Oncology Group
name: NCIC Clinical Trials Group
name: Mario Negri Institute for Pharmacological Research
name: UNICANCER
First posted: 2006-12-13
Enrollment: 670
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Overall survival
timeFrame: 5 years
measure: Failure-free survival
timeFrame: 5 years
Secondary outcomes:
measure: Quality of life by QLQ-C30 v3.0
timeFrame: 5 years
measure: Severe treatment-related morbidity
timeFrame: 5 years
measure: Vaginal or pelvic relapse
timeFrame: 5 years
measure: Distant metastases
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: 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.
citation: 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.
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 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.
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 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.
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