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

NCT ID: NCT04989647

Last Updated: 2023-09-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

514 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-06-10

Study Completion Date

2032-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Cervical Cancer

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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

Group Type EXPERIMENTAL

No adjuvant therapy

Intervention Type RADIATION

Patients will not receive any type of adjuvant therapy.

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

Group Type EXPERIMENTAL

Adjuvant radiotherapy

Intervention Type RADIATION

Patients will receive adjuvant treatment composed of either pelvic radiotherapy external beam radiotherapy ± brachytherapy or concomitant chemoradiotherapy (pelvic radiotherapy + chemotherapy).

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

No adjuvant therapy

Patients will not receive any type of adjuvant therapy.

Intervention Type RADIATION

Adjuvant radiotherapy

Patients will receive adjuvant treatment composed of either pelvic radiotherapy external beam radiotherapy ± brachytherapy or concomitant chemoradiotherapy (pelvic radiotherapy + chemotherapy).

Intervention Type RADIATION

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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)

* 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
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

The Central and Eastern European Gynecologic Oncology Group

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

David Cibula

prof. David Cibula, MD, PhD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

David Cibula, prof.

Role: PRINCIPAL_INVESTIGATOR

General University Hospital in Prague, Czech Republic

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

General University Hospital in Prague

Prague, , Czechia

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

Czechia

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Martina Borcinova, PhD

Role: CONTACT

+420224969298

Trial Office

Role: CONTACT

+420224967432

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Martina Borcinova

Role: primary

+420224969298

References

Explore related publications, articles, or registry entries linked to this study.

Sedlis A, Bundy BN, Rotman MZ, Lentz SS, Muderspach LI, Zaino RJ. A randomized trial of pelvic radiation therapy versus no further therapy in selected patients with stage IB carcinoma of the cervix after radical hysterectomy and pelvic lymphadenectomy: A Gynecologic Oncology Group Study. Gynecol Oncol. 1999 May;73(2):177-83. doi: 10.1006/gyno.1999.5387.

Reference Type BACKGROUND
PMID: 10329031 (View on PubMed)

Rotman M, Sedlis A, Piedmonte MR, Bundy B, Lentz SS, Muderspach LI, Zaino RJ. A phase III randomized trial of postoperative pelvic irradiation in Stage IB cervical carcinoma with poor prognostic features: follow-up of a gynecologic oncology group study. Int J Radiat Oncol Biol Phys. 2006 May 1;65(1):169-76. doi: 10.1016/j.ijrobp.2005.10.019. Epub 2006 Jan 19.

Reference Type BACKGROUND
PMID: 16427212 (View on PubMed)

Scharl S, Becher C, Gerken M, Scharl A, Anapolski M, Ignatov A, Inwald EC, Ortmann O, Kolbl O, Klinkhammer-Schalke M, Papathemelis T. Is there a benefit for adjuvant radio(chemo)therapy in early cervical cancer? Results from a population-based study. Arch Gynecol Obstet. 2021 Sep;304(3):759-771. doi: 10.1007/s00404-021-05989-w. Epub 2021 Feb 11.

Reference Type BACKGROUND
PMID: 33575846 (View on PubMed)

Kim SI, Kim TH, Lee M, Kim HS, Chung HH, Lee TS, Jeon HW, Kim JW, Park NH, Song YS. Impact of Adjuvant Radiotherapy on Survival Outcomes in Intermediate-Risk, Early-Stage Cervical Cancer: Analyses Regarding Surgical Approach of Radical Hysterectomy. J Clin Med. 2020 Nov 3;9(11):3545. doi: 10.3390/jcm9113545.

Reference Type BACKGROUND
PMID: 33153125 (View on PubMed)

Cibula D, Abu-Rustum NR, Fischerova D, Pather S, Lavigne K, Slama J, Alektiar K, Ming-Yin L, Kocian R, Germanova A, Fruhauf F, Dostalek L, Dusek L, Narayan K. Surgical treatment of "intermediate risk" lymph node negative cervical cancer patients without adjuvant radiotherapy-A retrospective cohort study and review of the literature. Gynecol Oncol. 2018 Dec;151(3):438-443. doi: 10.1016/j.ygyno.2018.10.018. Epub 2018 Oct 20.

Reference Type BACKGROUND
PMID: 30348519 (View on PubMed)

van der Velden J, Mom CH, van Lonkhuijzen L, Tjiong MY, Westerveld H, Fons G. Analysis of isolated loco-regional recurrence rate in intermediate risk early cervical cancer after a type C2 radical hysterectomy without adjuvant radiotherapy. Int J Gynecol Cancer. 2019 Jun 2;29(5):874-878. doi: 10.1136/ijgc-2019-000445.

Reference Type BACKGROUND
PMID: 31133601 (View on PubMed)

Cao L, Wen H, Feng Z, Han X, Zhu J, Wu X. Role of adjuvant therapy after radical hysterectomy in intermediate-risk, early-stage cervical cancer. Int J Gynecol Cancer. 2021 Jan;31(1):52-58. doi: 10.1136/ijgc-2020-001974. Epub 2020 Dec 10.

Reference Type BACKGROUND
PMID: 33303568 (View on PubMed)

Akilli H, Tohma YA, Bulut AN, Karakas LA, Haberal AN, Kuscu UE, Ayhan A. Comparison of no adjuvant treatment and radiotherapy in early-stage cervical carcinoma with intermediate risk factors. Int J Gynaecol Obstet. 2020 Jun;149(3):298-302. doi: 10.1002/ijgo.13147. Epub 2020 Apr 22.

Reference Type BACKGROUND
PMID: 32246761 (View on PubMed)

Nasioudis D, Latif NA, Giuntoli Ii RL, Haggerty AF, Cory L, Kim SH, Morgan MA, Ko EM. Role of adjuvant radiation therapy after radical hysterectomy in patients with stage IB cervical carcinoma and intermediate risk factors. Int J Gynecol Cancer. 2021 Jun;31(6):829-834. doi: 10.1136/ijgc-2021-002489. Epub 2021 May 6.

Reference Type BACKGROUND
PMID: 33962994 (View on PubMed)

Rogers L, Siu SS, Luesley D, Bryant A, Dickinson HO. Radiotherapy and chemoradiation after surgery for early cervical cancer. Cochrane Database Syst Rev. 2012 May 16;2012(5):CD007583. doi: 10.1002/14651858.CD007583.pub3.

Reference Type BACKGROUND
PMID: 22592722 (View on PubMed)

Bilek K, Ebeling K, Leitsmann H, Seidel G. Radical pelvic surgery versus radical surgery plus radiotherapy for stage Ib carcinoma of the cervix uteri. Preliminary results of a prospective randomized clinical study. Arch Geschwulstforsch. 1982 May;52(3):223-9.

Reference Type BACKGROUND
PMID: 6751268 (View on PubMed)

Schorge JO, Molpus KL, Koelliker D, Nikrui N, Goodman A, Fuller AF Jr. Stage IB and IIA cervical cancer with negative lymph nodes: the role of adjuvant radiotherapy after radical hysterectomy. Gynecol Oncol. 1997 Jul;66(1):31-5. doi: 10.1006/gyno.1997.4691.

Reference Type BACKGROUND
PMID: 9234917 (View on PubMed)

Kridelka FJ, Berg DO, Neuman M, Edwards LS, Robertson G, Grant PT, Hacker NF. Adjuvant small field pelvic radiation for patients with high risk, stage IB lymph node negative cervix carcinoma after radical hysterectomy and pelvic lymph node dissection. A pilot study. Cancer. 1999 Nov 15;86(10):2059-65.

Reference Type BACKGROUND
PMID: 10570432 (View on PubMed)

Hong JH, Tsai CS, Lai CH, Chang TC, Wang CC, Lee SP, Tseng CJ, Hsueh S. Postoperative low-pelvic irradiation for stage I-IIA cervical cancer patients with risk factors other than pelvic lymph node metastasis. Int J Radiat Oncol Biol Phys. 2002 Aug 1;53(5):1284-90. doi: 10.1016/s0360-3016(02)02831-6.

Reference Type BACKGROUND
PMID: 12128131 (View on PubMed)

Pieterse QD, Trimbos JB, Dijkman A, Creutzberg CL, Gaarenstroom KN, Peters AA, Kenter GG. Postoperative radiation therapy improves prognosis in patients with adverse risk factors in localized, early-stage cervical cancer: a retrospective comparative study. Int J Gynecol Cancer. 2006 May-Jun;16(3):1112-8. doi: 10.1111/j.1525-1438.2006.00600.x.

Reference Type BACKGROUND
PMID: 16803494 (View on PubMed)

Chen SW, Liang JA, Yang SN, Lin FJ. Early stage cervical cancer with negative pelvic lymph nodes: pattern of failure and complication following radical hysterectomy and adjuvant radiotherapy. Eur J Gynaecol Oncol. 2004;25(1):81-6.

Reference Type BACKGROUND
PMID: 15053068 (View on PubMed)

Cibula D, Slama J, Dostalek L, Fischerova D, Germanova A, Fruhauf F, Dundr P, Nemejcova K, Jarkovsky J, Sebestova S, Burgetova A, Borcinova M, Kocian R. Tumour-free distance: a novel prognostic marker in patients with early-stage cervical cancer treated by primary surgery. Br J Cancer. 2021 Mar;124(6):1121-1129. doi: 10.1038/s41416-020-01204-w. Epub 2020 Dec 14.

Reference Type BACKGROUND
PMID: 33318656 (View on PubMed)

Cibula D, Potter R, Planchamp F, Avall-Lundqvist E, Fischerova D, Haie Meder C, Kohler C, Landoni F, Lax S, Lindegaard JC, Mahantshetty U, Mathevet P, McCluggage WG, McCormack M, Naik R, Nout R, Pignata S, Ponce J, Querleu D, Raspagliesi F, Rodolakis A, Tamussino K, Wimberger P, Raspollini MR. The European Society of Gynaecological Oncology/European Society for Radiotherapy and Oncology/European Society of Pathology guidelines for the management of patients with cervical cancer. Radiother Oncol. 2018 Jun;127(3):404-416. doi: 10.1016/j.radonc.2018.03.003. Epub 2018 May 1.

Reference Type BACKGROUND
PMID: 29728273 (View on PubMed)

Cibula D, Borcinova M, Kocian R, Feltl D, Argalacsova S, Dvorak P, Fischerova D, Dundr P, Jarkovsky J, Hoschlova E, Slama J, Scambia G. CERVANTES: an international randomized trial of radical surgery followed by adjuvant (chemo) radiation versus no further treatment in patients with early-stage, intermediate-risk cervical cancer (CEEGOG-CX-05; ENGOT-CX16). Int J Gynecol Cancer. 2022 Oct 3;32(10):1327-1331. doi: 10.1136/ijgc-2022-003918.

Reference Type DERIVED
PMID: 36100282 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

ENGOT-cx16/CEEGOG/CERVANTES

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.