Evaluating surgery with or without additional radiotherapy for intermediate risk cervical cancer

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

This study is testing if adding radiation therapy after surgery helps people with intermediate risk cervical cancer live longer without their cancer coming back.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 514 (estimated)
• Ages: 18 Years to 85 Years
• Sex: Female
• Sponsor: The Central and Eastern European Gynecologic Oncology Group (other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Prague)
• Trial ID: NCT04989647 on ClinicalTrials.gov

What this trial studies

This trial aims to determine whether adjuvant (chemo)radiotherapy improves disease-free survival in patients with intermediate risk cervical cancer after radical surgery. A total of 514 patients will be enrolled and randomly assigned to receive either no additional treatment or adjuvant radiotherapy following surgery. The study will assess the primary endpoint of disease-free survival using a Cox proportional hazards model, with a focus on providing high-quality evidence regarding the effectiveness of adjuvant treatment in this patient population.

Who should consider this trial

Good fit: Ideal candidates include patients with pathologically confirmed invasive cervical cancer classified as FIGO IB1-IIA and exhibiting specific tumor-related risk factors.

Not a fit: Patients with adenosquamous cancer or unusual types of adenocarcinoma, as well as those with evidence of lymph node involvement or distant metastases, may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide critical insights into the role of adjuvant therapy, potentially improving outcomes for patients with intermediate risk cervical cancer.

How similar studies have performed: Previous studies have shown mixed results regarding the role of adjuvant treatment in similar patient populations, making this trial a significant effort to clarify the issue.

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

Where this trial is running

Prague

• General University Hospital in Prague — Prague, Czechia (RECRUITING)

Study contacts

• Principal investigator: David Cibula, prof. — General University Hospital in Prague, Czech Republic
• Study coordinator: Martina Borcinova, PhD

Conditions: Cervical Cancer, intermediate risk cervical cancer, adjuvant radiotherapy, disease free survival