Randomized Trial of Radiation Therapy With or Without Chemotherapy for Endometrial Cancer (PORTEC-3)

October 10, 2023 updated by: Carien Creutzberg, Leiden University

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

670

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Leiden, Netherlands, 2300 RC
        • Leiden University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Radiation Therapy
Pelvic Radiotherapy alone
Radiation: Radiation Therapy
External beam pelvic radiotherapy (48.6 Gy in 1.8 Gy fractions) Vaginal brachytherapy boost in case of cervical involvement
Other Names:
  • RT
  • IMRT
  • brachytherapy
  • 3D conformal radiotherapy
Experimental: Radiation Therapy and Chemotherapy
Pelvic Radiation plus 2 concurrent cycles cisplatin followed by 4 adjuvant cycles carboplatin and paclitaxel
Radiation: Radiation Therapy
External beam pelvic radiotherapy (48.6 Gy in 1.8 Gy fractions) Vaginal brachytherapy boost in case of cervical involvement
Other Names:
  • RT
  • IMRT
  • brachytherapy
  • 3D conformal radiotherapy
Drug: cisplatin
cisplatin 50 mg/m2 i.v., 2 cycles during radiotherapy, 3 wks interval
Other Names:
  • Cisplatine
Drug: carboplatin
carboplatin AUC 5, 4 cycles after completion of radiotherapy, 3 wks interval
Other Names:
  • Carboplatine
  • Carbotaxol
Drug: Paclitaxel
paclitaxel 175 mg/m2, 4 cycles after completion of radiotherapy, 3 wks interval
Other Names:
  • Taxol
  • Taxolcarbo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: 5 years
co-primary endpoint
5 years
Failure-free survival
Time Frame: 5 years
co-primary endpoint
5 years

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Leiden University

Collaborators

Cancer Research UK
NCIC Clinical Trials Group
Mario Negri Institute for Pharmacological Research
UNICANCER
Australia New Zealand Gynaecological Oncology Group

Investigators

  • Study Chair: Carien L. Creutzberg, MD, PhD, Leiden University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 23, 2006

Primary Completion (Actual)

November 29, 2018

Study Completion (Estimated)

December 31, 2024

Study Registration Dates

First Submitted

December 11, 2006

First Submitted That Met QC Criteria

December 11, 2006

First Posted (Estimated)

December 13, 2006

Study Record Updates

Last Update Posted (Actual)

October 11, 2023

Last Update Submitted That Met QC Criteria

October 10, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000521447; P06.031
  • CKTO-2006-04 (Other Grant/Funding Number: Dutch Cancer Society)
  • ISRCTN14387080 (Registry Identifier: International Standard Randomised Controlled Trial Number)
  • P06.031-PORTEC-3 (Other Identifier: Leiden University Medical Center)
  • 2007-004917-33 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Sharing of data will be an option after publication of long-term outcomes and after submission of a research plan with is approved by the with international TMG

IPD Sharing Time Frame

Anticipated in 218

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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