Chemotherapy Followed By Surgery Vs Radiotherapy Plus Chemotherapy in Patients With Stage IB or II Cervical Cancer

NCT ID: NCT00039338

Last Updated: 2016-12-05

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

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

686 participants

Study Classification

INTERVENTIONAL

Study Start Date

2002-03-31

Brief Summary

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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving chemotherapy drugs before surgery may shrink the tumor so that it can be removed during surgery. Radiation therapy uses high-energy x-rays to kill tumor cells. Combining radiation therapy with chemotherapy may kill more tumor cells. It is not yet known whether chemotherapy is more effective followed by surgery or combined with radiation therapy in treating cervical cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy followed by radical hysterectomy with that of chemotherapy plus radiation therapy in treating patients who have stage IB or stage II cervical cancer.

Detailed Description

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OBJECTIVES:

* Compare the overall and progression-free survival of patients with stage IB2, IIA, or IIB cervical cancer treated with neoadjuvant cisplatin-based chemotherapy followed by radical hysterectomy vs standard therapy comprising concurrent radiotherapy and cisplatin-based chemotherapy.
* Compare the toxicity of these regimens in these patients.
* Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, FIGO stage, age (18 to 50 vs 51 to 75), and histological subtype (adenomatous vs non-adenomatous component). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive neoadjuvant cisplatin-based chemotherapy on day 1. Treatment repeats every 21 days. Within 6 weeks after the last chemotherapy course, patients undergo a type III-V Piver-Rutledge radical hysterectomy. Patients with positive lymph nodes or tumor invasion into the parametria or less than 5 mm from the resection borders after surgery receive standard adjuvant external beam radiotherapy once daily, 5 days a week, for 5-5.6 weeks (25-28 treatment days) followed by external boost radiotherapy or brachytherapy for 1 or 2 days.
* Arm II: Patients receive standard therapy comprising radiotherapy as in arm I concurrently with cisplatin-based chemotherapy once weekly for 6 weeks. Adjuvant hysterectomy is allowed, but not recommended, in case of histologically proven residual tumor.

Treatment in both arms continues in the absence of disease progression or unacceptable toxicity. For patients in both arms, cisplatin may be combined with other chemotherapeutics as long as the minimum platinum dose is given.

Quality of life is assessed at baseline and at 6, 12, 18, and 24 months.

Patients are followed every 3 months for 1 year, every 6 months for 4 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 686 patients (343 per treatment arm) will be accrued for this study within 3.8 years.

Conditions

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Cervical Cancer

Keywords

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stage IB cervical cancer stage IIB cervical cancer stage IIA cervical cancer cervical squamous cell carcinoma cervical adenocarcinoma cervical adenosquamous cell carcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Chemotherapy followed by surgery

neoadjuvant chemotherapy (Cisplatin) followed by surgery (radial hysterectomy)

Group Type EXPERIMENTAL

conventional surgery

Intervention Type PROCEDURE

Radial hysterectomy

neoadjuvant chemotherapy

Intervention Type PROCEDURE

Experimental arm: minimal cumulative cisplatin dose of 225 mg/m2. Comparator arm: cumulative cisplatin dose of 200-240 mg/m2.

cisplatin

Intervention Type DRUG

Minimal cumulative 225 mg/m2 (experimental arm). Cumulative 200-240 mg/m2 (comparator arm).

Radio-chemotherapy

Concomitant radiotherapy (external radiotherapy combined with external boost or brachytherapy) and chemotherapy (cisplatin)

Group Type ACTIVE_COMPARATOR

neoadjuvant chemotherapy

Intervention Type PROCEDURE

Experimental arm: minimal cumulative cisplatin dose of 225 mg/m2. Comparator arm: cumulative cisplatin dose of 200-240 mg/m2.

brachytherapy

Intervention Type RADIATION

Brachytherapy at the end of external radiation. Minimal total dose (external with or without external boost + brachytherapy) of 75 Gy EQD2 to point A. Overall treatment less than 50 days.

radiation therapy

Intervention Type RADIATION

Between 45-50 Gy, in fractions of 1.8 to 2 Gy.

cisplatin

Intervention Type DRUG

Minimal cumulative 225 mg/m2 (experimental arm). Cumulative 200-240 mg/m2 (comparator arm).

Interventions

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conventional surgery

Radial hysterectomy

Intervention Type PROCEDURE

neoadjuvant chemotherapy

Experimental arm: minimal cumulative cisplatin dose of 225 mg/m2. Comparator arm: cumulative cisplatin dose of 200-240 mg/m2.

Intervention Type PROCEDURE

brachytherapy

Brachytherapy at the end of external radiation. Minimal total dose (external with or without external boost + brachytherapy) of 75 Gy EQD2 to point A. Overall treatment less than 50 days.

Intervention Type RADIATION

radiation therapy

Between 45-50 Gy, in fractions of 1.8 to 2 Gy.

Intervention Type RADIATION

cisplatin

Minimal cumulative 225 mg/m2 (experimental arm). Cumulative 200-240 mg/m2 (comparator arm).

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

DISEASE CHARACTERISTICS:

* Histologically confirmed cervical cancer, including the following subtypes:

* Squamous cell carcinoma
* Adenosquamous cell carcinoma
* Adenocarcinoma (excluding small cell, clear cell, and other rare variants of the classical adenocarcinoma)
* FIGO stage IB2, IIA (greater than 4 cm), or IIB

PATIENT CHARACTERISTICS:

Age:

* 18 to 75

Performance status:

* WHO 0-2

Life expectancy:

* Not specified

Hematopoietic:

* Absolute neutrophil count greater than 1,500/mm\^3
* Platelet count greater than 100,000/mm\^3

Hepatic:

* Bilirubin less than 1.46 mg/dL

Renal:

* Creatinine clearance greater than 60 mL/min

Other:

* No other prior or concurrent malignancy except adequately treated basal cell skin cancer
* No psychological, familial, sociological, or geographical condition that would preclude study
* Not pregnant

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* No prior chemotherapy

Endocrine therapy:

* Not specified

Radiotherapy:

* No prior radiotherapy

Surgery:

* Not specified

Other:

* No other concurrent anticancer agent
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Fabio Landoni, MD

Role: STUDY_CHAIR

Istituto Europeo Di Oncologia, Milano

Alessandro Colombo, MD

Role: STUDY_CHAIR

Ospedale Alessandro Manzoni, Lecco

Stefano Greggi, MD, PhD

Role: STUDY_CHAIR

Istituto Nazionale per lo Studio e la Cura dei Tumori, Napoli

Gemma G. Kenter, MD

Role: STUDY_CHAIR

Academisch Medisch Centrum - Universiteit van Amsterdam

Locations

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Karl-Franzens-University Graz

Graz, , Austria

Site Status

Kaiser Franz Josef Hospital

Vienna, , Austria

Site Status

Universitair Ziekenhuis Antwerpen

Edegem, , Belgium

Site Status

U.Z. Gasthuisberg

Leuven, , Belgium

Site Status

Centre Hospitalier Regional de la Citadelle

Liège, , Belgium

Site Status

Centre Regional Francois Baclesse

Caen, , France

Site Status

Istituto Europeo Di Oncologia

Milan, , Italy

Site Status

Ospedale San Gerardo

Monza, , Italy

Site Status

Istituto Nazionale Per Lo Studio E La Cura Dei Tumori

Naples, , Italy

Site Status

Ospedale Mauriziano Umberto I

Torino, , Italy

Site Status

Clinica Universitaria

Turin, , Italy

Site Status

Ospedale di Circolo e Fondazione Macchi

Varese, , Italy

Site Status

Academisch Medisch Centrum at University of Amsterdam

Amsterdam, , Netherlands

Site Status

Vrije Universiteit Medisch Centrum

Amsterdam, , Netherlands

Site Status

Medisch Spectrum Twente

Enschede, , Netherlands

Site Status

Leiden University Medical Center

Leiden, , Netherlands

Site Status

Universitair Medisch Centrum St. Radboud - Nijmegen

Nijmegen, , Netherlands

Site Status

Erasmus MC - Daniel den Hoed Cancer Center

Rotterdam, , Netherlands

Site Status

Universitair Medisch Centrum - Academisch Ziekenhuis

Utrecht, , Netherlands

Site Status

Hospitais da Universidade de Coimbra (HUC)

Coimbra, , Portugal

Site Status

Hospital Universitario San Carlos

Madrid, , Spain

Site Status

Queen Elizabeth The Queen Mother Hospital

Margate, England, United Kingdom

Site Status

NHS Greater Glasgow and Clyde - Beatson West of Scotland Cancer Centre

Glasgow, Scotland, United Kingdom

Site Status

Mid Kent Oncology Centre

Maidstone, Kent, , United Kingdom

Site Status

Countries

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Argentina Poland Austria Belgium France Italy Netherlands Portugal Spain United Kingdom

References

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Kenter GG, Greggi S, Vergote I, Katsaros D, Kobierski J, van Doorn H, Landoni F, van der Velden J, Reed N, Coens C, van Luijk I, Colombo N, Steen-Banasik EV, Ottevanger N, Casado A; EORTC-55994 Study Group. Randomized Phase III Study Comparing Neoadjuvant Chemotherapy Followed by Surgery Versus Chemoradiation in Stage IB2-IIB Cervical Cancer: EORTC-55994. J Clin Oncol. 2023 Nov 10;41(32):5035-5043. doi: 10.1200/JCO.22.02852. Epub 2023 Sep 1.

Reference Type DERIVED
PMID: 37656948 (View on PubMed)

Other Identifiers

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2008-003396-52

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EORTC-55994

Identifier Type: -

Identifier Source: org_study_id