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

Sponsor
The Central and Eastern European Gynecologic Oncology Group (Other)
Overall Status
Recruiting
CT.gov ID
NCT04989647
Collaborator
(none)
514
Enrollment
1
Location
2
Arms
125.7
Anticipated Duration (Months)
4.1
Patients Per Site Per Month

Study Details

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%).

Condition or Disease Intervention/Treatment Phase
  • Radiation: No adjuvant therapy
  • Radiation: Adjuvant radiotherapy
 Phase 3

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 Design

Study Type:
Interventional
Anticipated Enrollment :
514 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jun 10, 2022
Anticipated Primary Completion Date :
Dec 1, 2029
Anticipated Study Completion Date :
Dec 1, 2032

Arms and Interventions

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).

Outcome Measures

Primary Outcome Measures

  1. Disease-free survival [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.

Secondary Outcome Measures

  1. Overall survival [Analysed 6 years after randomization of the last patient.]

  2. Pelvic disease-free survival [Analysed 3 years after randomization of the last patient.]

  3. Health-related quality of life based questionnaire [Analysed 3 years after randomization of the last patient.]

    The analysis will be made based on EORTC validated questionnaires and developed qualitative CERVANTES questionnaire.

  4. Treatment-related adverse events based on Common Terminology Criteria for Adverse Events v5.0 [Analysed 3 years after randomization of the last patient.]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 85 Years
Sexes Eligible for Study:
Female
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 General University Hospital in Prague Prague Czechia 12000

Sponsors and Collaborators

  • The Central and Eastern European Gynecologic Oncology Group

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
David Cibula, prof. David Cibula, MD, PhD, General University Hospital, Prague
ClinicalTrials.gov Identifier:
NCT04989647
Other Study ID Numbers:
  • ENGOT-cx16/CEEGOG/CERVANTES
First Posted:
Aug 4, 2021
Last Update Posted:
Jul 26, 2022
Last Verified:
Jul 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
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
Keywords provided by David Cibula, prof. David Cibula, MD, PhD, General University Hospital, Prague
intermediate risk cervical cancer
adjuvant radiotherapy
disease free survival
Additional relevant MeSH terms:
Uterine Cervical Neoplasms

Study Results

No Results Posted as of Jul 26, 2022