Back to resultsIntermediate Risk Cervical Cancer: Radical Surgery +/- Adjuvant Radiotherapy (CERVANTES)
Primary Purpose
Cervical Cancer
Status
Recruiting
Phase
Phase 3
Locations
Czechia
Study Type
Interventional
Intervention
No adjuvant therapy
Adjuvant radiotherapy
Sponsored by
About this trial
This is an interventional treatment trial for Cervical Cancer focused on measuring intermediate risk cervical cancer, adjuvant radiotherapy, disease free survival
Eligibility Criteria
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:
- tumour ≥4 cm OR
- tumour>2 cm <4 cm AND lymphovascular space invasion OR
- tumour >2 cm <4 cm AND tumour free distance <3 mm OR
- 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
Sites / Locations
- General University Hospital in PragueRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
A: Surgery only
B: Surgery + radiothrerapy
Arm Description
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
Radical hysterectomy, sentinel lymph node biopsy and systematic pelvic lymphadenectomy (PLND)*, followed by adjuvant treatment. *PLND can be avoided in patients with tumours < 4cm
Outcomes
Primary Outcome Measures
Disease-free survival
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.
Secondary Outcome Measures
Overall survival
Pelvic disease-free survival
Health-related quality of life based questionnaire
The analysis will be made based on EORTC validated questionnaires and developed qualitative CERVANTES questionnaire.
Treatment-related adverse events based on Common Terminology Criteria for Adverse Events v5.0
Full Information
NCT ID
NCT04989647
First Posted
July 29, 2021
Last Updated
September 5, 2023
Sponsor
The Central and Eastern European Gynecologic Oncology Group
1. Study Identification
Unique Protocol Identification Number
NCT04989647
Brief Title
Intermediate Risk Cervical Cancer: Radical Surgery +/- Adjuvant Radiotherapy
Acronym
CERVANTES
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 10, 2022 (Actual)
Primary Completion Date
December 2029 (Anticipated)
Study Completion Date
December 2032 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The Central and Eastern European Gynecologic Oncology Group
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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%).
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cervical Cancer
Keywords
intermediate risk cervical cancer, adjuvant radiotherapy, disease free survival
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
514 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
A: Surgery only
Arm Type
Experimental
Arm Description
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
Arm Title
B: Surgery + radiothrerapy
Arm Type
Experimental
Arm Description
Radical hysterectomy, sentinel lymph node biopsy and systematic pelvic lymphadenectomy (PLND)*, followed by adjuvant treatment.
*PLND can be avoided in patients with tumours < 4cm
Intervention Type
Radiation
Intervention Name(s)
No adjuvant therapy
Intervention Description
Patients will not receive any type of adjuvant therapy.
Intervention Type
Radiation
Intervention Name(s)
Adjuvant radiotherapy
Intervention Description
Patients will receive adjuvant treatment composed of either pelvic radiotherapy external beam radiotherapy ± brachytherapy or concomitant chemoradiotherapy (pelvic radiotherapy + chemotherapy).
Primary Outcome Measure Information:
Title
Disease-free survival
Description
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.
Time Frame
Analysed 3 years after randomization of the last patient.
Secondary Outcome Measure Information:
Title
Overall survival
Time Frame
Analysed 6 years after randomization of the last patient.
Title
Pelvic disease-free survival
Time Frame
Analysed 3 years after randomization of the last patient.
Title
Health-related quality of life based questionnaire
Description
The analysis will be made based on EORTC validated questionnaires and developed qualitative CERVANTES questionnaire.
Time Frame
Analysed 3 years after randomization of the last patient.
Title
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.
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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:
tumour ≥4 cm OR
tumour>2 cm <4 cm AND lymphovascular space invasion OR
tumour >2 cm <4 cm AND tumour free distance <3 mm OR
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Martina Borcinova, PhD
Phone
+420224969298
Email
martina.borcinova@cervantes-trial.com
First Name & Middle Initial & Last Name or Official Title & Degree
Trial Office
Phone
+420224967432
Email
trial.office@cervantes-trial.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Cibula, prof.
Organizational Affiliation
General University Hospital in Prague, Czech Republic
Official's Role
Principal Investigator
Facility Information:
Facility Name
General University Hospital in Prague
City
Prague
ZIP/Postal Code
12000
Country
Czechia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Martina Borcinova
Phone
+420224969298
Email
martina.borcinova@cervantes-trial.com
12. IPD Sharing Statement
Plan to Share IPD
No
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Intermediate Risk Cervical Cancer: Radical Surgery +/- Adjuvant Radiotherapy
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