Selective Targeting of Adjuvant Therapy for Endometrial Cancer (STATEC) (STATEC)

A Randomised Trial of Non-selective Versus Selective Adjuvant Therapy in High Risk Apparent Stage 1 Endometrial Cancer

The primary aim of this trial is to determine whether lymphadenectomy, used to restrict adjuvant therapy (other than vaginal brachytherapy) to node positive women, results in a non-inferior survival as compared to adjuvant therapy given to all women with high risk apparent stage 1 endometrial cancer.

Study Overview

• Status: Terminated
• Conditions: Endometrial Cancer
• Intervention / Treatment: Procedure: Abdominal surgery; Procedure: Lymphadenectomy

Detailed Description

Results from this trial have the potential to change practice whatever the results: either lymphadenectomy will become recommended practice if a non-inferior outcome is obtained; otherwise the procedure can be safely abandoned.

Secondary Objectives

• Disease-free, endometrial cancer-event free and endometrial cancer-specific survival
• Distribution of pelvic and extra-pelvic relapse
• Cost effectiveness
• Surgical adverse events

There are also two sub-studies:

1. Quality of life - all patients i. Describe the trajectory of key patient reported outcomes (PROs) from baseline up to 5 years post-surgery ii. Compare the specific PRO domains between the trial arms at several specific time points iii. Determine the proportion of women in each trial arm reporting long-term symptoms after treatment as measured by the symptom-specific subscales of the measures (gastrointestinal symptoms, urological symptoms, attitude to disease and treatment, vaginal symptoms, lymphoedema) iv. Determine the correlation between physician rating (CTCAE v4.03) and patient-report (corresponding PRO subscale) for various symptoms reported by both physicians and patients v. Assess the correlation between self-assessed lymphoedema (Self-report lower-extremity lymphoedema screening questionnaire) and the lymphoedema subscale of the Quality of Life Questionnaire-Endometrial Cancer Module (QLQ-EN24)

   We hypothesise that quality of life will be better in patients in the lymphadenectomy arm because a considerable proportion will be spared systemic adjuvant treatment, from which they may not benefit.

2. Sentinel lymph node (SLN) - optional for Arm 1 patients

The aim of this sub-study is to assess SLN status in comparison with the overall lymph node status after full lymph node dissection (LND), and so determine whether SLN is as accurate as systematic node dissection.

i. We aim to determine the diagnostic performance of the SLN procedure compared to the gold standard of LND ii. To evaluate whether SLN status is a prognostic marker of survival iii. To model patient relapse and survival based on low volume micro-metastatic (LVM) and individual tumour cell (ITC) status

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Greater London
    • London, Greater London, United Kingdom
      • University College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Histologically confirmed high risk apparent International Federation of Gynecology and Obstetrics (FIGO) stage I endometrial cancer according to one of the following criteria. Confirmation must be based on either diagnostic endometrial sampling or hysterectomy and BSO specimen if randomisation occurring after hysterectomy and BSO:

  1. FIGO grade 3 endometrioid or mucinous carcinoma
  2. High grade serous, clear cell, undifferentiated or dedifferentiated carcinoma or mixed cell adenocarcinoma or carcinosarcoma
• Surgery to be performed ≤ 5 weeks after randomisation in patients randomised prior to hysterectomy and BSO. Patients randomised after hysterectomy and BSO must have undergone hysterectomy and BSO ≤ 28 days prior to randomisation. Patients randomised after hysterectomy and BSO who are allocated lymphadenectomy must undergo lymphadenectomy ≤ 5 weeks after randomisation
• Written informed consent
• No prior anticancer therapy for endometrial cancer
• Eastern Cooperative Oncology Group (EGOC) performance status 0-2
• Life expectancy > 3 months
• Age ≥ 16 years
• Adequate organ and bone marrow function
• Ability to undergo post-operative chemotherapy with or without radiotherapy
• Adjuvant treatment to commence ≤ 8 weeks after surgery
• Willingness and ability to complete Quality of Life questionnaires

Exclusion Criteria:

• Grossly enlarged node(s) of ≥ 10 mm short axis on baseline radiological imaging
• Invasion of the cervical stroma on baseline radiological imaging or obvious cervical disease on clinical examination
• Involvement of uterine serosa or metastatic disease seen outside the uterus on baseline radiological imaging
• Small cell carcinoma with neuroendocrine differentiation
• Concurrent anti-cancer therapy

• Previous malignancy < 5 years prior to randomisation or concurrent malignant disease with the exception of:

  1. carcinoma in situ of cervix
  2. non-melanoma skin cancer
  3. basal cell carcinoma
  4. melanoma in situ
• Women who are pregnant or lactating

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: Abdominal surgery with lymphadenectomy; Patients will receive a hysterectomy and bilateral salpingo-oophorectomy (BSO)* with lymph node dissection to determine whether lymph nodes are positive or negative: Positive: patients will receive systemic adjuvant treatment to include chemotherapy Negative: patients will receive vaginal brachytherapy only Patients will then be followed up, to include assessment of adverse events and quality of life. *There is an option for patients to be randomised following a pre-trial hysterectomy and BSO. If randomised to this arm, the lymph node dissection will be performed as a separate procedure.	Procedure: Abdominal surgery; Hysterectomy defined as an extrafascial hysterectomy whereby the cervix is removed completely but no radical dissection of the parametria is required; Procedure: Lymphadenectomy; Bilateral pelvic and para-aortic lymph node dissection
Active Comparator: Abdominal surgery, no lymphadenectomy; Patients will receive a hysterectomy and bilateral salpingo-oophorectomy (BSO)*. Patients will receive systemic adjuvant treatment to include chemotherapy. Patients will then be followed up, to include assessment of adverse events and quality of life. *There is an option for patients to be randomised following a pre-trial hysterectomy and BSO. If randomised to this arm, no further surgery will be given and the patient will proceed to receive systemic adjuvant treatment to include chemotherapy.	Procedure: Abdominal surgery; Hysterectomy defined as an extrafascial hysterectomy whereby the cervix is removed completely but no radical dissection of the parametria is required

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free survival	Disease-free survival	5 years
Endometrial cancer-event free survival	Endometrial cancer-event free survival	5 years
Endometrial cancer-specific survival	Endometrial cancer-specific survival	5 years
Pelvic and extra-pelvic relapse-free survival		5 years
Cost effectiveness	Cost effectiveness	5 years
Surgical adverse events	Surgical adverse events	5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life- Patient Reported Outcomes	Quality of life	5 years
Accuracy, sensitivity and specificity (i.e. diagnostic performance) of sentinel lymph node (SLN) assessment, and the ratio of sensitivity to false positive rate (called likelihood ratio)	Accuracy, sensitivity and specificity (i.e. diagnostic performance) of sentinel lymph node	5 years

Collaborators and Investigators

• Sponsor: University College, London
• Investigators: Principal Investigator: Tim Mould, University College London Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2017
• Primary Completion (Actual): August 14, 2019
• Study Completion (Actual): August 14, 2019

Study Registration Dates

• First Submitted: September 22, 2015
• First Submitted That Met QC Criteria: October 1, 2015
• First Posted (Estimate): October 2, 2015

Study Record Updates

• Last Update Posted (Actual): September 30, 2019
• Last Update Submitted That Met QC Criteria: September 26, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Endometrial Neoplasms
• Other Study ID Numbers: UCL/13/0630

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No