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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Cancer Research UK
Australia New Zealand Gynaecological Oncology Group
NCIC Clinical Trials Group
Mario Negri Institute for Pharmacological Research
UNICANCER
Information provided by (Responsible Party):
Carien Creutzberg, Leiden University Medical Center
ClinicalTrials.gov Identifier:
NCT00411138
First received: December 11, 2006
Last updated: August 28, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Endometrial Cancer
Radiation: Radiation Therapy
Drug: cisplatin
Drug: carboplatin
Drug: Paclitaxel
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Leiden University Medical Center:

Primary Outcome Measures:
  • Overall survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Failure-free survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Quality of life by QLQ-C30 v3.0 [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Severe treatment-related morbidity [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
    Acute serious events and SAE and late grade 3 complications

  • Rate of vaginal or pelvic relapse [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Rate of distant metastases [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 670
Study Start Date: October 2006
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
  • 3D conformal radiotherapy
  • IMRT
  • brachytherapy
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
  • 3D conformal radiotherapy
  • IMRT
  • brachytherapy
Drug: cisplatin
cisplatin 50 mg/m2 i.v., 2 cycles during radiotherapy, 3 wks interval
Other Name: 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

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

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00411138

Locations
Netherlands
Leiden University Medical Center
Leiden, Netherlands, 2300 RC
Sponsors and Collaborators
Leiden University Medical Center
Cancer Research UK
Australia New Zealand Gynaecological Oncology Group
NCIC Clinical Trials Group
Mario Negri Institute for Pharmacological Research
UNICANCER
Investigators
Study Chair: Carien L. Creutzberg, MD, PhD Leiden University Medical Center
  More Information

Additional Information:
Publications:
Responsible Party: Carien Creutzberg, Chief Investigator, Leiden University Medical Center
ClinicalTrials.gov Identifier: NCT00411138     History of Changes
Other Study ID Numbers: CDR0000521447; P06.031, CKTO-2006-04, ISRCTN14387080, P06.031-PORTEC-3, 2007-004917-33
Study First Received: December 11, 2006
Last Updated: August 28, 2014
Health Authority: Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by Leiden University Medical Center:
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

Additional relevant MeSH terms:
Paclitaxel
Cisplatin
Carboplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on September 29, 2014