Clinical trial NCT04989647: Intermediate Risk Cervical Cancer: Radical Surgery +/- Adjuvant Radiotherapy
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
Overall status: RECRUITING
Phase: PHASE3
Conditions: Cervical Cancer
Keywords: intermediate risk cervical cancer
adjuvant radiotherapy
disease free survival
Lead sponsor: The Central and Eastern European Gynecologic Oncology Group
Sponsor class: OTHER
First posted: 2021-08-04
Enrollment: 514
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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:

  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

Primary outcomes:
measure: Disease-free survival
timeFrame: Analysed 3 years after randomization of the last patient.
Secondary outcomes:
measure: Overall survival
timeFrame: Analysed 6 years after randomization of the last patient.
measure: Pelvic disease-free survival
timeFrame: Analysed 3 years after randomization of the last patient.
measure: Health-related quality of life based questionnaire
timeFrame: Analysed 3 years after randomization of the last patient.
measure: Treatment-related adverse events based on Common Terminology Criteria for Adverse Events v5.0
timeFrame: Analysed 3 years after randomization of the last patient.
Other outcomes:
Locations:
city: Prague
country: Czechia
facility: General University Hospital in Prague
Study officials:
affiliation: General University Hospital in Prague, Czech Republic
name: David Cibula, prof.
role: PRINCIPAL_INVESTIGATOR
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