Radical Versus Simple Hysterectomy and Pelvic Node Dissection With Low-risk Early Stage Cervical Cancer

Cervical Cancer Clinical Trial

— SHAPE  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01658930
• Other study ID #: CX5
• Status: Active, not recruiting
• Phase: N/A
• Start date: December 10, 2012
• Est. completion date: December 31, 2024

Study information

• Verified date: February 2024
• Source: Canadian Cancer Trials Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 700
• Est. completion date: December 31, 2024
• Est. primary completion date: March 11, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cervical Cancer
• Uterine Cervical Neoplasms

Intervention

Procedure:
• Radical Hysterectomy + pelvic lymph node dissection
This procedure may be performed abdominally, laparoscopically, robotically or vaginally. The uterus, cervix, medial 1/3 of parametria, 2cm of the uterosacral ligaments and upper 1-2cm of the vagina are to be removed en bloc. The uterine artery is ligated laterally to the ureters and the ureters are unroofed to the ureterovesical junction.
• Simple hysterectomy + pelvic lymph node dissection
This procedure may be performed abdominally, laparoscopically, robotically or vaginally. Extrafascial hysterectomy involves removal of the uterus with cervix without adjacent parametria. The uterine arteries are transected medial to the ureters at the level of the isthmus and the uterosacral ligaments are transected at the level of the cervix. Surgeons should pay special attention to make sure that the whole cervix is removed. As such, a maximum of 0.5 cm of vaginal cuff can be removed to ensure the complete removal of the cervix.

Locations

Country	Name	City	State
Austria	Barmherzige Brueder Graz	Graz
Austria	Medical University of Graz	Graz
Austria	Medical University of Innsbruck	Innsbruck
Austria	LKH Leoben	Leoben
Austria	Landes- Frauen- und Kinderklinik Linz	Linz
Austria	LKH Salzburg	Salzburg
Austria	Medical University of Vienna	Vienna
Belgium	UZ Leuven	Leuven	Vlaams-Brabant
Belgium	CHR de la Citadelle liege	Liege
Belgium	CHU Sart Tilman Liege	Liege
Canada	Royal Victoria Regional Health Centre	Barrie	Ontario
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	QEII Health Sciences Centre	Halifax	Nova Scotia
Canada	London Regional Cancer Program	London	Ontario
Canada	Trillium Health Partners - Credit Valley Hospital	Mississauga	Ontario
Canada	CHUM-Centre Hospitalier de l'Universite de Montreal	Montreal	Quebec
Canada	CIUSSS de l'Est-de-I'lle-de-Montreal	Montreal	Quebec
Canada	The Jewish General Hospital	Montreal	Quebec
Canada	Ottawa Hospital Research Institute	Ottawa	Ontario
Canada	CIUSSS de l'Estrie - Centre hospitalier	Sherbrooke	Quebec
Canada	University Health Network	Toronto	Ontario
Canada	Clinical Research Unit at Vancouver Coastal	Vancouver	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba
China	Shanghai Cancer Center	Shanghai
France	CHU Amiens	Amiens
France	Institut Bergonie Bordeaux	Bordeaux
France	CHRU de Brest	Brest
France	CHU de Chambery	Chambery
France	Centre Jean Perrin - Clermont-Ferrand	Clermont Ferrand
France	CHU de Clermont-Ferrand	Clermont-Ferrand
France	Centre Georges Francois Leclerc - Dijon	Dijon
France	CHU de Dijon	Dijon
France	Centre Oscar Lambret - Lille	Lille
France	CHRU de Lille	Lille
France	CHU Limoges	Limoges
France	Centre Leon Berard - Lyon	Lyon
France	Hospices Civils de Lyon	Lyon
France	Institut Paoli Calmettes - Marseille	Marseille
France	Institut Regional du Cancer de Montpellier	Montpellier
France	Institut Arnault Tzank - Mougins	Mougins
France	CHU de Nice	Nice
France	CHU de Nimes	Nimes
France	Hopital Europeen Georges Pompidou - Paris	Paris
France	CHU de Reims	Reims
France	CHU de Rennes	Rennes
France	Clinique Mutualiste de la Sagesse - Rennes	Rennes
France	Clinique Mathilde - Rouen	Rouen
France	ICO - Rene Gauducheau	Saint-Herblain
France	CHU de Strasbourg	Strasbourg
France	CHU de Bordeaux	Talence
France	Institut Claudius Regaud - Toulouse	Toulouse
France	CHRU de Tours	Tours
Germany	Hochtaunus-Kliniken gGmbH	Bad Homburg
Germany	DRK Kliniken Berlin Koepenick	Berlin
Germany	DRK Klinikum Berlin Westend	Berlin
Germany	Martin-Luther-Krankenhaus Berlin	Berlin
Germany	GYNAEKOLOGICUM Bremen	Bremen
Germany	Kaiserswerther Diakonie - Florence-Nightingale-Krankenhaus	Duesseldorf
Germany	Universitaetsfrauenklinik Duesseldorf	Duesseldorf
Germany	Kliniken Essen Mitte	Essen
Germany	Universitaetsfrauenklinik Freiburg	Freiburg
Germany	Universitaetsfrauenklinik Greifswald	Greifswald
Germany	Agaplesion Diakonieklinikum Hamburg	Hamburg
Germany	Universitaetsklinikum Hamburg - Eppendorf	Hamburg
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Universitaetsklinikum des Saarlandes	Homburg-Saar
Germany	Universitaetsfrauenklinik Jena	Jena
Germany	Universitaetsfrauenklinik Luebeck	Luebeck
Germany	Universitaetsfrauenklinik Mainz	Mainz
Germany	Klinikum der Universitaet Muenchen - LMU Campus Grosshadern	Muenchen
Germany	Universitaetsfrauenklinik Tuebingen	Tuebingen
Germany	Universitaetsfrauenklinik Ulm	Ulm
Germany	Marien-Hospital Witten	Witten
Ireland	St James Hospital	Dublin	Leinster
Netherlands	LUMC	Leiden
Netherlands	Erasmus MC	Rotterdam
Norway	Oslo University Hospital	Oslo	Postboks 4953 Nydalen
Russian Federation	Hertzen Moscow Scientific Research	Moscow
United Kingdom	East Kent Hospitals University NHS Foundation Trust	Canterbury	Ethelbert Road
United Kingdom	South Tees Hospitals NHS Foundation Trust	Middlesbrough	Marton Road
United Kingdom	Queen Alexandra Hospital	Portsmouth
United Kingdom	Sheffield Teaching Hospitals NHS Foundation Trust	Sheffield	Glossop Road
United Kingdom	Royal Cornwall Hospital	Truro	Cornwall
United Kingdom	Southend University Hospital	Westcliff-on-Sea	Essex

Sponsors (14)

Lead Sponsor

Collaborator

Canadian Cancer Trials Group

Arbeitsgemeinschaft Gynaekologische Onkologie Austria, Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom Germany, Belgium Gynecologic Oncology Group, Canadian Institutes of Health Research (CIHR), Cancer Trials Ireland, Dutch Gynecologic Oncology Group, Group d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens, Gynecologic Cancer Intergroup (GCIG), Hertzen Moscow Scientific Research Institute of Oncology, Institut Claudius Regaud - Institute Universitaire du Cancer de Toulouse - Oncopole, Institute of Cancer Research, United Kingdom, Korean Gynecologic Oncology Group, Shanghai Cancer Centre Deptartment of Gynecologic Oncology Fudan University

Countries where clinical trial is conducted

Austria,  Belgium,  Canada,  China,  France,  Germany,  Ireland,  Netherlands,  Norway,  Russian Federation,  United Kingdom, 

References & Publications (1)

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 SH — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pelvic recurrence rate at 3 years	Pelvic relapse-free survival (PRFS), the primary endpoint of this study, is defined as the time from randomization to the time of documented evidence of recurrence within the pelvic field.	7 years
Secondary	Efficacy comparison between treatment arms	compare the two treatment arms with respect to: pelvic relapse-free survival; Extra pelvic relapse-free survival; Relapse-free survival (any site); Overall survival; Treatment-related adverse events; Patient Reported Outcomes including global quality of life and measures of sexual health; Cost-effectiveness and cost-utility; To observe the rates of the following in this patient population: sentinel node detection.; Parametrial involvement; Involvement of surgical margins; Pelvic node involvement	7 years