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

• ClinicalTrials.gov Identifier: NCT01658930
• Recruitment Status: Active, not recruiting
• First Posted: August 7, 2012
• Last Update Posted: February 15, 2023
• Sponsor: Canadian Cancer Trials Group
• Collaborators: Gynecologic Cancer Intergroup (GCIG); Canadian Institutes of Health Research (CIHR); Korean Gynecologic Oncology Group; Dutch Gynecologic Oncology Group; Cancer Trials Ireland; Arbeitsgemeinschaft Gynaekologische Onkologie Austria; Belgium Gynecologic Oncology Group; Group d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens; Institute of Cancer Research, United Kingdom; Shanghai Cancer Centre Deptartment of Gynecologic Oncology Fudan University; Hertzen Moscow Scientific Research Institute of Oncology; Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom Germany; Institut Claudius Regaud - Institute Universitaire du Cancer de Toulouse - Oncopole
• Information provided by (Responsible Party): Canadian Cancer Trials Group

Tracking Information

• First Submitted Date: August 3, 2012
• First Posted Date: August 7, 2012
• Last Update Posted Date: February 15, 2023
• Actual Study Start Date: August 2, 2012
• Estimated Primary Completion Date: June 30, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 18, 2022)

Pelvic recurrence rate at 3 years [ Time Frame: 7 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.

Original Primary Outcome Measures (submitted: August 6, 2012)

Pelvic relapse-free survival [ Time Frame: 7 years ]

Pelvic relapse-free survival (PRFS), the primary endpoint of this study, is defined as the time from randomization to the time when any documented evidence of recurrence within the pelvic field.

Current Secondary Outcome Measures (submitted: July 18, 2022)

Efficacy comparison between treatment arms [ Time Frame: 7 years ]

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

Original Secondary Outcome Measures (submitted: August 6, 2012)

• Efficacy comparison between treatment arms [ Time Frame: 7 years ]
  compare the two treatment arms with respect to:

  • Extrapelvic relapse-free survival
  • Relapse-free survival (any site)
  • Overall survival
  • Treatment-related toxicity
  • Patient Reported Outcomes including global quality of life and measures of sexual health
  • Cost-effectiveness and cost-utility
• Occurrence rates in patient population [ Time Frame: 7 years ]
  observe rates of the following in this patient population:

  • Sentinel node detection
  • Parametrial involvement
  • Involvement of surgical margins
  • Pelvic node involvement

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• 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.
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Cervical Cancer

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.
• Procedure: 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.

Study Arms

• Active Comparator: Radical Hysterectomy
  Intervention: Procedure: Radical Hysterectomy + pelvic lymph node dissection
• Experimental: Simple Hysterectomy
  Intervention: Procedure: Simple hysterectomy + pelvic lymph node dissection

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: August 6, 2012): 700
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2023
• Estimated Primary Completion Date: June 30, 2023 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, Belgium, Canada, China, France, Germany, Ireland, Netherlands, Norway, Russian Federation, United Kingdom

Administrative Information

• NCT Number: NCT01658930
• Other Study ID Numbers: CX5
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Canadian Cancer Trials Group
• Original Responsible Party: NCIC Clinical Trials Group
• Current Study Sponsor: Canadian Cancer Trials Group
• Original Study Sponsor: NCIC Clinical Trials Group

Collaborators

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

Investigators

• Study Chair: Marie Plante; Canadian Cancer Trials Group
• Study Chair: Gwenael Ferron; France-GINECO
• Study Chair: Jae-Weon Kim; Korean Gynecology Oncology Group
• Study Chair: Christian Marth; Arbeitsgemeinschaft Gynaekologische Onkologie Austria
• Study Chair: John Tidy; Institute of Cancer Research, United Kingdom
• Study Chair: Noreen Gleeson; Ireland Co-operative Oncology Research Group
• Study Chair: Frederic Goffin; Belgian Gynaecological Oncology Group
• Study Chair: Cor de Kroon; The Dutch Gynecological Oncology Group (DGOG)
• Study Chair: Xiaohua Wu; Fudan University
• Study Chair: Sven Mahner; AGO Germany
• Study Chair: Brynhildur Eyjolfsdottir; Oslo University Hospital
• Study Chair: Alexey Shevchuk; Hertzen Institute, Moscow

• PRS Account: Canadian Cancer Trials Group
• Verification Date: July 2022