Intermediate Risk Cervical Cancer: Radical Surgery +/- Adjuvant Radiotherapy (CERVANTES)

September 5, 2023 updated by: David Cibula, The Central and Eastern European Gynecologic Oncology Group

An International Randomised Trial of Radical Surgery Followed by Adjuvant (Chemo)Radiation Versus no Further Treatment in Patients With Early-stage, Intermediate-risk Cervical Cancer Patients

The objective of the trial is to evaluate if adjuvant (chemo)radiation is associated with a disease-free survival benefit after radical surgery in patients with intermediate risk cervical cancer. The primary endpoint of the study is the disease-free survival from the day of randomisation. A total of 514 patients are required to achieve 80% power on 5% significance level with non-inferiority margin of 5% to test the difference between the ARMs using Cox proportional hazards model. The maximal tolerated margin for non-inferiority in 2-year DFS is 5% (including expected drop-out rate of 10%).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The role of adjuvant (chemo)radiotherapy in intermediate risk (IR) cervical cancer patients is controversial, supported by single randomised GOG 92 study performed more than 20 years ago. Intermediate-risk group is defined as lymph node negative but with a combination of negative prognostic factors (tumour size >2 cm, lymphovascular space invasion, deep stromal invasion >2/3). Recent retrospective studies showed excellent local control in intermediate risk group patients after radical surgery with no additional adjuvant treatment.

CERVANTES trial is designed to bring level A evidence on the role of adjuvant treatment in IR patients in an international, prospective, randomised study. Patients will be registered into the trial before surgery and randomised after the final pathology report has been received into ARM A, with no additional treatment, and ARM B, receiving adjuvant (chemo)radiotherapy. Quality assurance program will be in place for both, radical surgery and adjuvant treatment.

Study Type

Interventional

Enrollment (Estimated)

514

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Pathologically confirmed invasive cervical cancer
  • FIGO IB1-IIA
  • Squamous cell cancer or HPV-related adenocarcinoma

  • Presence of tumour-related risk factors as follows:

    1. tumour ≥4 cm OR
    2. tumour>2 cm <4 cm AND lymphovascular space invasion OR
    3. tumour >2 cm <4 cm AND tumour free distance <3 mm OR
    4. tumour >2 cm <4 cm AND deep stromal invasion (>2/3)
  • No evidence of suspicious pelvic lymph nodes or distant metastases on imaging (by radiological subjective assessment before surgery and negative pelvic LN on final pathology)
  • ECOG performance status 0-1
  • Deemed suitable and fit for radical surgery followed by adjuvant radiotherapy
  • Negative pregnancy test (if applicable)
  • Negative HIV test (only performed in high-risk countries or patients who have moved from those countries within the past 10 years)

Exclusion Criteria:

  • Adenosquamous cancer or adenocarcinoma unusual type (non-HPV related - such as: mucinous, clear cell, mesonephric) or other rare tumour types (those not listed in the inclusion criteria)
  • Inconclusive primary site of disease
  • Unequivocally positive lymph node by imaging (by radiological subjective assessment)
  • FIGO <IB1 / >IIA
  • Previous pelvic malignancy
  • History of second primary cancer outside pelvis if ≤ 3 years complete clinical remission (CCR)
  • Previous pelvic radiotherapy
  • Neoadjuvant chemotherapy prior surgical treatment
  • Low likelihood of patient compliance to the follow-up

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: A: Surgery only

Radical hysterectomy, sentinel lymph node biopsy and systematic pelvic lymphadenectomy (PLND)*. No further treatment will be administered.

*PLND can be avoided in patients with tumours < 4cm
Radiation: No adjuvant therapy
Patients will not receive any type of adjuvant therapy.
Experimental: B: Surgery + radiothrerapy

Radical hysterectomy, sentinel lymph node biopsy and systematic pelvic lymphadenectomy (PLND)*, followed by adjuvant treatment.

*PLND can be avoided in patients with tumours < 4cm
Radiation: Adjuvant radiotherapy
Patients will receive adjuvant treatment composed of either pelvic radiotherapy external beam radiotherapy ± brachytherapy or concomitant chemoradiotherapy (pelvic radiotherapy + chemotherapy).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease-free survival
Time Frame: Analysed 3 years after randomization of the last patient.
Calculated as an interval from the day of randomisation until diagnosis of recurrence: (a) unequivocal finding on imaging by subjective radiological assessment; b) suspicious recurrence on imaging either confirmed by biopsy or supported by other signs (disease progression on imaging or progression of symptoms); (c) physical examination supported by clinical evidence (i.e., symptoms or progression); or (d) death caused by disease or death of unknown cause.
Analysed 3 years after randomization of the last patient.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: Analysed 6 years after randomization of the last patient.
Analysed 6 years after randomization of the last patient.
Pelvic disease-free survival
Time Frame: Analysed 3 years after randomization of the last patient.
Analysed 3 years after randomization of the last patient.
Health-related quality of life based questionnaire
Time Frame: Analysed 3 years after randomization of the last patient.
The analysis will be made based on EORTC validated questionnaires and developed qualitative CERVANTES questionnaire.
Analysed 3 years after randomization of the last patient.
Treatment-related adverse events based on Common Terminology Criteria for Adverse Events v5.0
Time Frame: Analysed 3 years after randomization of the last patient.
Analysed 3 years after randomization of the last patient.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Central and Eastern European Gynecologic Oncology Group

Investigators

  • Principal Investigator: David Cibula, prof., General University Hospital in Prague, Czech Republic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 10, 2022

Primary Completion (Estimated)

December 1, 2029

Study Completion (Estimated)

December 1, 2032

Study Registration Dates

First Submitted

July 29, 2021

First Submitted That Met QC Criteria

July 29, 2021

First Posted (Actual)

August 4, 2021

Study Record Updates

Last Update Posted (Actual)

September 7, 2023

Last Update Submitted That Met QC Criteria

September 5, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ENGOT-cx16/CEEGOG/CERVANTES

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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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