Clinical trial NCT01658930: Radical Versus Simple Hysterectomy and Pelvic Node Dissection With Low-risk Early Stage Cervical Cancer
Official title: A Randomized Phase III Trial Comparing Radical Hysterectomy and Pelvic Node Dissection vs Simple Hysterectomy and Pelvic Node Dissection in Patients With Low-Risk Early Stage Cervical Cancer (SHAPE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cervical Cancer
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
Collaborators: name: Gynecologic Cancer Intergroup (GCIG)
name: Canadian Institutes of Health Research (CIHR)
name: Korean Gynecologic Oncology Group
name: Dutch Gynaecological Oncology Group
name: Cancer Trials Ireland
name: Arbeitsgemeinschaft Gynaekologische Onkologie Austria
name: Belgian Gynaecological Oncology Group
name: ARCAGY/ GINECO GROUP
name: Institute of Cancer Research, United Kingdom
name: Shanghai Cancer Centre
name: P. Herzen Moscow Oncology Research Institute
name: Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom Germany
name: Institut Universitaire du Cancer de Toulouse
First posted: 2012-08-07
Enrollment: 700
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The reason this study is being done is to see if a simple hysterectomy is as good as a radical hysterectomy in preventing cancer of the cervix from returning, and whether, because less tissue surrounding the uterus is removed during surgery, there are fewer side-effects after the surgery and in the long-term.

Detailed description: At this time, it is not clear which of these approaches best balances the desire to prevent cancer of the cervix from returning with the risks of side effects after surgery and in the long-term.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed adenocarcinoma, squamous, or adenosquamous cancer of the cervix. Diagnosis has been made by LEEP, cone or cervical biopsy and has been reviewed and confirmed by the local reference gynecological pathologist.
* Patient has been classified as low-risk early-stage cervical cancer. These patients include:

  • FIGO Stage IA2 \[FIGO Annual Report, 2009\], defined as:

  o evidence of disease by microscopy;
* for patients who underwent a LEEP or cone:

  * histologic evidence of depth of stromal invasion \> 3.0 and ≤ 5.0 mm based on the local reference pathologist's measurement of the LEEP or cone specimen NB: the maximum depth of stromal invasion must be ≤ 10 mm.
  * histologic evidence of lateral extension that is ≤ 7.0 mm based on the local reference pathologist's measurement of the LEEP or cone specimen; and
  * negative margins (patients with positive margins are considered IB1, see below)
* for patients who underwent a cervical biopsy only:

  * radiologic evidence of less than 50% stromal invasion based on pelvic MRI

    • FIGO Stage IB1 \[FIGO Annual Report, 2009\] with favorable (low risk) features, defined as:
  * measured stromal invasion and lateral extension that meet the criteria for IA2 (see above) but with positive margins;
  * evidence of disease by clinical exam; lesion must clinically measure ≤ 20 mm
  * evidence of disease by microscopy;
* for patients who underwent a LEEP or cone:

  * histologic evidence of depth of stromal invasion between 5.1-10 mm and/or lateral extension between 7.1-20.0 mm based on the local reference pathologist's measurement of the LEEP or cone specimen
* for patients who underwent a cervical biopsy only:
* radiologic evidence of less than 50% stromal invasion based on pelvic MRI
* lateral extension ≤ 20 mm based on clinical exam or radiologic imaging.

In addition to above criteria on maximal stromal invasion of ≤ 10 mm, the lesion must be no larger than 20 mm in any dimension by any assessment method (MRI, clinical or histological exam). To ensure patients meet this criterion, investigators may need to sum the lesion measurements from biopsy and other methods that evaluate it in the same plane.

Patients are eligible irrespective of the presence or absence of lymph-vascular space involvement (LVSI).

* Physical examination, recto-vaginal examination and visualization of the cervix by speculum or colposcopic examination have been done after the initial diagnostic procedure (LEEP, cone or biopsy) and prior to randomization.
* Chest x-ray or CT scan of chest AND pelvic MRI\* done after initial diagnostic procedure (LEEP, cone or biopsy) and prior to randomization.

The CT should be a 16 slice (or higher) helical scanner. Oral and intravenous contrasts are preferred (unless there is a contraindication to the use of contrast) with scan obtained in the portal phase at a slice thickness of 5mm or lower Pelvic MRI should be performed on a 1.5 or 3 Tesla magnet with pelvic phased-array coils. The MR pulse sequences will consist of T1 gradient echo in the axial plane at 5 mm slice thickness and fast spin echo in the axial, sagittal, and coronal planes at 4 mm slice thickness. The short axis (perpendicular to the tumour's long axis) with a 3 mm slice thickness is required in the best plane to show the maximum thickness of stromal invasion. Use of an anti-peristaltic agent is mandatory while intravenous use of gadolinium or diffusion-weighted imaging (DWI) is optional.

\* Note: pelvic MRI is optional if the patient has stage IA2 disease and underwent a LEEP or cone.

* After consideration of a patient's medical history, physical examination and laboratory testing, patients must be suitable candidates for surgery as defined by the attending physician / investigator.
* Patients must have no desire to preserve fertility.
* Patients fluent in English or French must be willing to complete the Quality of Life Questionnaire. The baseline assessments must be completed within 6 weeks prior to randomization. Inability (illiteracy in English or French, loss of sight, or other equivalent reason) to complete the questionnaires will not make the patient ineligible for the study. However, ability but unwillingness to complete the questionnaires will make the patient ineligible. As additional GCIG groups join the study, more translations of some of the questionnaires may be added.

Patients fluent in English or French who reside in Canada and the United Kingdom must agree to participate in the economic evaluation component of this trial and complete the Health Economics Questionnaire. Similarly, patients fluent in English or French accrued from other GCIG groups who are participating in the economic evaluation must be willing to complete the Health Economics Questionnaires.

* Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrolment in the trial to document their willingness to participate.
* Patients must be accessible for treatment and follow-up. Investigators must assure themselves the patients randomized on this trial will be available for complete documentation of the treatment, adverse events, and follow-up.
* Surgery is to be done within 20 weeks of initial diagnosis (NO EXCEPTIONS). The 20-week period includes time required for diagnosis, referral, diagnostic staging, randomization and scheduling of the surgical procedure.
* Patients must be ≥ 18 years old.

Exclusion Criteria:

* Patients with FIGO 1A1 disease \[FIGO Annual Report, 2009\].
* History of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours, Hodgkin's lymphoma or non-Hodgkin's lymphoma curatively treated with no evidence of disease for \> 5 years.
* Patients with evidence of lymph node metastasis on preoperative imaging or histology.
* Patients who have had or will receive neoadjuvant chemotherapy.
* Patients who are pregnant.
* Patients for whom adjuvant radiation and/or chemotherapy is planned.

Primary outcomes:
measure: Pelvic Recurrence Rate at 3 Years
timeFrame: 3 years
Secondary outcomes:
measure: Pelvic Relapse-free Survival
timeFrame: 3 years
measure: Extra-pelvic Relapse-free Survival
timeFrame: 3 years
measure: Relapse-free Survival
timeFrame: 3 years
measure: Overall Survival
timeFrame: 3 years
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Barmherzige Brueder Graz
city: Graz
country: Austria
facility: Medical University of Graz
city: Innsbruck
country: Austria
facility: Medical University of Innsbruck
city: Leoben
country: Austria
facility: LKH Leoben
city: Linz
country: Austria
facility: Landes- Frauen- und Kinderklinik Linz
city: Salzburg
country: Austria
facility: LKH Salzburg
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Leuven
country: Belgium
facility: UZ Leuven
state: Vlaams-Brabant
city: Liege
country: Belgium
facility: CHR de la Citadelle liege
city: Liege
country: Belgium
facility: CHU Sart Tilman Liege
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Vancouver
country: Canada
facility: Clinical Research Unit at Vancouver Coastal
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Halifax
country: Canada
facility: QEII Health Sciences Centre
state: Nova Scotia
city: Barrie
country: Canada
facility: Royal Victoria Regional Health Centre
state: Ontario
city: London
country: Canada
facility: London Regional Cancer Program
state: Ontario
city: Mississauga
country: Canada
facility: Trillium Health Partners - Credit Valley Hospital
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Greenfield Park
country: Canada
state: Quebec
city: Montreal
country: Canada
facility: CIUSSS de l'Est-de-I'lle-de-Montreal
state: Quebec
city: Montreal
country: Canada
facility: CHUM-Centre Hospitalier de l'Universite de Montreal
state: Quebec
city: Montreal
country: Canada
facility: The Jewish General Hospital
state: Quebec
city: Quebec City
country: Canada
state: Quebec
city: Sherbrooke
country: Canada
facility: CIUSSS de l'Estrie - Centre hospitalier
state: Quebec
city: Shanghai
country: China
facility: Shanghai Cancer Center
city: Amiens
country: France
facility: CHU Amiens
city: Bordeaux
country: France
facility: Institut Bergonie Bordeaux
city: Brest
country: France
facility: CHRU de Brest
city: Chambery
country: France
facility: CHU de Chambery
city: Clermont Ferrand
country: France
facility: Centre Jean Perrin - Clermont-Ferrand
city: Clermont-Ferrand
country: France
facility: CHU de Clermont-Ferrand
city: Dijon
country: France
facility: Centre Georges Francois Leclerc - Dijon
city: Dijon
country: France
facility: CHU de Dijon
city: Lille
country: France
facility: Centre Oscar Lambret - Lille
city: Lille
country: France
facility: CHRU de Lille
city: Limoges
country: France
facility: CHU Limoges
city: Lyon
country: France
facility: Hospices Civils de Lyon
city: Lyon
country: France
facility: Centre Leon Berard - Lyon
city: Marseille
country: France
facility: Institut Paoli Calmettes - Marseille
city: Montpellier
country: France
facility: Institut Regional du Cancer de Montpellier
city: Mougins
country: France
facility: Institut Arnault Tzank - Mougins
city: Nice
country: France
facility: CHU de Nice
city: Nimes
country: France
facility: CHU de Nimes
city: Paris
country: France
facility: Hopital Europeen Georges Pompidou - Paris
city: Reims
country: France
facility: CHU de Reims
city: Rennes
country: France
facility: CHU de Rennes
city: Rennes
country: France
facility: Clinique Mutualiste de la Sagesse - Rennes
city: Rouen
country: France
facility: Clinique Mathilde - Rouen
city: Saint-Herblain
country: France
facility: ICO - Rene Gauducheau
city: Strasbourg
country: France
facility: CHU de Strasbourg
city: Talence
country: France
facility: CHU de Bordeaux
city: Toulouse
country: France
facility: Institut Claudius Regaud - Toulouse
city: Tours
country: France
facility: CHRU de Tours
city: Bad Homburg
country: Germany
facility: Hochtaunus-Kliniken gGmbH
city: Berlin
country: Germany
facility: DRK Kliniken Berlin Koepenick
city: Berlin
country: Germany
facility: DRK Klinikum Berlin Westend
city: Berlin
country: Germany
facility: Martin-Luther-Krankenhaus Berlin
city: Bremen
country: Germany
facility: GYNAEKOLOGICUM Bremen
city: Duesseldorf
country: Germany
facility: Universitaetsfrauenklinik Duesseldorf
city: Duesseldorf
country: Germany
facility: Kaiserswerther Diakonie - Florence-Nightingale-Krankenhaus
city: Essen
country: Germany
facility: Kliniken Essen Mitte
city: Freiburg
country: Germany
facility: Universitaetsfrauenklinik Freiburg
city: Greifswald
country: Germany
facility: Universitaetsfrauenklinik Greifswald
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg - Eppendorf
city: Hamburg
country: Germany
facility: Agaplesion Diakonieklinikum Hamburg
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Homburg-Saar
country: Germany
facility: Universitaetsklinikum des Saarlandes
city: Jena
country: Germany
facility: Universitaetsfrauenklinik Jena
city: Luebeck
country: Germany
facility: Universitaetsfrauenklinik Luebeck
city: Mainz
country: Germany
facility: Universitaetsfrauenklinik Mainz
city: Muenchen
country: Germany
facility: Klinikum der Universitaet Muenchen - LMU Campus Grosshadern
city: Tuebingen
country: Germany
facility: Universitaetsfrauenklinik Tuebingen
city: Ulm
country: Germany
facility: Universitaetsfrauenklinik Ulm
city: Witten
country: Germany
facility: Marien-Hospital Witten
city: Dublin
country: Ireland
facility: St James Hospital
state: Leinster
city: Leiden
country: Netherlands
facility: LUMC
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Oslo
country: Norway
facility: Oslo University Hospital
state: Postboks 4953 Nydalen
city: Moscow
country: Russian Federation
facility: Hertzen Moscow Scientific Research
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital
state: Cornwall
city: Westcliff-on-Sea
country: United Kingdom
facility: Southend University Hospital
state: Essex
city: Canterbury
country: United Kingdom
facility: East Kent Hospitals University NHS Foundation Trust
state: Ethelbert Road
city: Sheffield
country: United Kingdom
facility: Sheffield Teaching Hospitals NHS Foundation Trust
state: Glossop Road
city: Middlesbrough
country: United Kingdom
facility: South Tees Hospitals NHS Foundation Trust
state: Marton Road
city: Portsmouth
country: United Kingdom
facility: Queen Alexandra Hospital
Study officials:
affiliation: Canadian Cancer Trials Group
name: Marie Plante
role: STUDY_CHAIR
affiliation: France-GINECO
name: Gwenael Ferron
role: STUDY_CHAIR
affiliation: Korean Gynecology Oncology Group
name: Jae-Weon Kim
role: STUDY_CHAIR
affiliation: Arbeitsgemeinschaft Gynaekologische Onkologie Austria
name: Christian Marth
role: STUDY_CHAIR
affiliation: Institute of Cancer Research, United Kingdom
name: John Tidy
role: STUDY_CHAIR
affiliation: Ireland Co-operative Oncology Research Group
name: Noreen Gleeson
role: STUDY_CHAIR
affiliation: Belgian Gynaecological Oncology Group
name: Frederic Goffin
role: STUDY_CHAIR
affiliation: The Dutch Gynecological Oncology Group (DGOG)
name: Cor de Kroon
role: STUDY_CHAIR
affiliation: Fudan University
name: Xiaohua Wu
role: STUDY_CHAIR
affiliation: AGO Germany
name: Sven Mahner
role: STUDY_CHAIR
affiliation: Oslo University Hospital
name: Brynhildur Eyjolfsdottir
role: STUDY_CHAIR
affiliation: Hertzen Institute, Moscow
name: Alexey Shevchuk
role: STUDY_CHAIR
References:
citation: Plante M, Kwon JS, Ferguson S, Samouelian V, Ferron G, Maulard A, de Kroon C, Van Driel W, Tidy J, Williamson K, Mahner S, Kommoss S, Goffin F, Tamussino K, Eyjolfsdottir B, Kim JW, Gleeson N, Brotto L, Tu D, Shepherd LE; CX.5 SHAPE investigators; CX.5 SHAPE Investigators. Simple versus Radical Hysterectomy in Women with Low-Risk Cervical Cancer. N Engl J Med. 2024 Feb 29;390(9):819-829. doi: 10.1056/NEJMoa2308900.