Prospective Randomised Phase II Trial Evaluating Adjuvant Pelvic Radiotherapy Using Either IMRT or 3-Dimensional Planning for Endometrial Cancer. ICORG 09-06

Prospective Randomised Phase II Trial Evaluating Adjuvant Pelvic Radiotherapy Using Either IMRT or 3-Dimensional Planning for Endometrial Cancer

Post-operative radiotherapy is internationally accepted as standard practice in the management of high-risk endometrial cancer1. Whilst it has no proven impact on overall survival it significantly increases local control.

Conventional radiotherapy techniques (3-dimensional) utilise a 3 or 4 field beam arrangement to target the pelvis in order to treat those areas at risk of recurrence: the vagina, the parametrium and the pelvic lymph nodes. However, when using such a technique it is not possible to avoid irradiating sensitive normal tissues such as the bowel and bladder.

Toxicity data from international randomised control trials in endometrial cancer report significantly more haematological, gastrointestinal, genitourinary and cutaneous toxicites (all grades) in those who received pelvic irradiation compared to those who did not2,3. These trials delivered radiotherapy using 2 or 3-dimensional techniques.

Intensity Modulated Radiation Therapy (IMRT) is a newer but established radiotherapy technique in many tumour sites that allows us to much more tightly conform the radiation. It uses computer-generated beams to produce radiotherapy volumes that can avoid irradiation of normal tissues in the pelvis.

There are no randomised studies reported in the literature that compare 3-dimensional pelvic irradiation with IMRT in patients who have had surgery for endometrial cancer. However there are several small studies that report considerable sparing of normal tissues using IMRT and when compared retrospectively with conventionally treated patients demonstrate marked reductions in acute gastrointestinal and genitourinary toxicity4.

By delivering post-operative radiotherapy to the pelvis using IMRT (as opposed to the standard 3-dimensional technique) it is anticipated that whilst local control and survival will be unaffected acute and late toxicity will be reduced.

Study Overview

• Status: Terminated
• Conditions: Endometrial Cancer; Radiation Toxicity; Gastrointestinal Complications; Urinary Complications
• Intervention / Treatment: Radiation: 45 Gy/25 fractions

Detailed Description

Primary Objective:

• To compare the incidence of acute grade >2 GU and GI toxicity

Secondary Objectives:

• To establish in the context of a clinical research study the feasibility of implementing pelvic nodal irradiation using IMRT in gynaecological cancer

• To establish an Image-Guided pathway for gynaecological cancer radiotherapy incorporating

  • Set-up errors and optimal margins for set-up uncertainty
  • Investigation of effects of bladder filling and rectal preparation protocols on the planning target volume
• To estimate the rate of loco-regional control
• To evaluate Quality of Life
• To estimate the rate of disease-free survival
• To estimate the overall survival rate
• To compare the incidence of late GU and GI toxicity

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Phase 2

Contacts and Locations

Study Locations

• Ireland
  • Dublin, Ireland, 6
    • St Luke's Radiation Oncology Network (SLRON) Centres
  • Dublin 6, Ireland
    • St Luke's Centre for Radiation Oncology at St Lukes Hospital
  • Dublin 8, Ireland
    • St Luke's Centre for Radiation Oncology at St James Hospital
  • Dublin 9, Ireland
    • St Luke's Centre for Radiation Oncology at Beaumont Hospital
  • Limerick, Ireland
    • Mid-Western Radiation Oncology Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Patients undergoing adjuvant pelvic radiotherapy for histologically confirmed endometrial adenocarcinoma / serous carcinoma / papillary serous carcinoma / mixed histology (adenocarcinoma and serous) and following AJCC 2009 grade/stage:

  • Grade 2: stage IB (LVSI +/or >60yrs)
  • Grade 3: stage IA and IB
  • Grade 1-3: Stage II and IIIA, IIIB and IIIC1
• Surgery consisting of total hysterectomy, +/- bilateral salpingo-oophorectomy, +/- lymph node sampling
• Staging with imaging of pelvis and abdomen (either MRI or CT)
• ECOG PS 0-2
• Age ≥ 18 years
• Provision of written informed consent in line with ICH-GCP guidelines

Exclusion Criteria:

• Previous radiotherapy to the pelvic region
• Patients in whom concurrent chemotherapy in planned
• Patients with macroscopic disease in situ
• History of inflammatory bowel disease
• Previous hip replacement
• Previous bowel surgery (excluding appendectomy)
• Patients with other syndromes/conditions associated with increased radiosensitivity
• The patient has or had other co-existing malignancies within the past 5 years other than non-melanoma skin cancer
• Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study or if it is felt by the research / medical team that the patient may not be able to comply with the protocol

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm B; Radiation: 45 Gy / 25 fractions pelvic radiotherapy using intensity modulated radiotherapy (IMRT) followed by 11 Gy / 2 fractions vaginal vault brachytherapy	Radiation: 45 Gy/25 fractions; Arm A 45 Gy/25 fractions pelvic radiotherapy using 3D planned technique followed by 11Gy/2 fractions vaginal vault brachytherapy
Other: Arm A Control; Radiation: 45 Gy/25 fraction external beam pelvic radiotherapy delivered using a 3-dimensional planned technique followed by 11 Gy / 2 fractions vaginal vault brachytherapy	Radiation: 45 Gy/25 fractions; Arm A 45 Gy/25 fractions pelvic radiotherapy using 3D planned technique followed by 11Gy/2 fractions vaginal vault brachytherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Reduction in the incidence of ≥ grade 2 acute genitourinary (GU) and gastrointestinal (GI) toxicity according to NCI CTCAE v.3.0	2015

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of late GI and GU toxicity according to NCI CTCAE v.3.0	2015
Feasibility of implementing pelvic nodal irradiation using intensity-modulated radiotherapy in gynecological cancer	2015
Establishment of an image-guided pathway for gynecological cancer radiotherapy	2015
Rate of loco-regional control as assessed by CT scan, MRI, and biopsy	2015
Quality of life as assessed using EORTC QLQ-C30 and EORTC QLQ Cervical Cancer Specific Module CX 24 questionnaires	2015
Rate of disease-free survival	2015
Overall survival rate	2015

Collaborators and Investigators

• Sponsor: Cancer Trials Ireland
• Investigators: Principal Investigator: Charles Gillham, Dr, Saint Luke's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2010
• Primary Completion (Actual): March 13, 2020
• Study Completion (Actual): March 13, 2020

Study Registration Dates

• First Submitted: July 15, 2010
• First Submitted That Met QC Criteria: July 15, 2010
• First Posted (Estimate): July 16, 2010

Study Record Updates

• Last Update Posted (Actual): April 6, 2023
• Last Update Submitted That Met QC Criteria: April 5, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: radiation toxicity; recurrent endometrial carcinoma; urinary complications; gastrointestinal complications; stage II endometrial carcinoma; stage IA endometrial carcinoma; stage IB endometrial carcinoma; stage IIIA endometrial carcinoma; stage IIIB endometrial carcinoma; stage IIIC endometrial carcinoma; endometrial adenocarcinoma
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Endometrial Neoplasms
• Other Study ID Numbers: CTRIAL-IE (ICORG) 09-06; EU-21048