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

Leiden University

Status and phase: Active, not recruiting; Phase 3

Conditions: Endometrial Cancer

Treatments: Drug: carboplatin; Drug: Paclitaxel; Radiation: Radiation Therapy; Drug: cisplatin

Study type: Interventional

Funder types: Other; NETWORK

Identifiers

NCT00411138

CKTO-2006-04 (Other Grant/Funding Number)

CDR0000521447 P06.031;

P06.031-PORTEC-3 (Other Identifier)

ISRCTN14387080 (Registry Identifier)

2007-004917-33 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 670 estimated patients

Sex: Female

Ages: 18 to 90 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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670 participants in 2 patient groups

Radiation Therapy

Active Comparator group

Description:

Pelvic Radiotherapy alone

Treatment:

Radiation: Radiation Therapy

Radiation Therapy and Chemotherapy

Experimental group

Description:

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

Treatment:

Drug: cisplatin

Radiation: Radiation Therapy

Drug: Paclitaxel

Drug: carboplatin