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

Cervical Cancer Clinical Trial

Official title:

Randomized Phase III Study Of Neoadjuvant Chemotherapy Followed By Surgery Vs. Concomitant Radiotherapy And Chemotherapy In FIGO Ib2, IIa>4 cm or IIb Cervical Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00039338
• Other study ID #: EORTC-55994
• Secondary ID: 2008-003396-52
• Status: Active, not recruiting
• Phase: Phase 3
• First received: June 6, 2002
• Last updated: December 2, 2016
• Start date: March 2002

Study information

• Verified date: December 2016
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Agency for Health and Food SafetyBelgium: Federal Agency for Medicinal Products and Health ProductsFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Italy: AIFA: Italian Drug AgencyPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsPortugal: National Authority of Medicines and Health ProductsSpain: Agencia Española de Medicamentos y Productos SanitariosNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 686
• Est. primary completion date: July 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cervical Cancer
• Uterine Cervical Neoplasms

Intervention

Procedure:
• conventional surgery
Radial hysterectomy
• neoadjuvant chemotherapy
Experimental arm: minimal cumulative cisplatin dose of 225 mg/m2. Comparator arm: cumulative cisplatin dose of 200-240 mg/m2.

Radiation:
• 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.
• radiation therapy
Between 45-50 Gy, in fractions of 1.8 to 2 Gy.

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

Locations

Country	Name	City	State
Austria	Karl-Franzens-University Graz	Graz
Austria	Kaiser Franz Josef Hospital	Vienna
Belgium	Universitair Ziekenhuis Antwerpen	Edegem
Belgium	U.Z. Gasthuisberg	Leuven
Belgium	Centre Hospitalier Regional de la Citadelle	Liege
France	Centre Regional Francois Baclesse	Caen
Italy	Istituto Europeo Di Oncologia	Milano
Italy	Ospedale San Gerardo	Monza
Italy	Istituto Nazionale Per Lo Studio E La Cura Dei Tumori	Naples
Italy	Ospedale Mauriziano Umberto I	Torino
Italy	Clinica Universitaria	Turin
Italy	Ospedale di Circolo e Fondazione Macchi	Varese
Netherlands	Academisch Medisch Centrum at University of Amsterdam	Amsterdam
Netherlands	Vrije Universiteit Medisch Centrum	Amsterdam
Netherlands	Medisch Spectrum Twente	Enschede
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Universitair Medisch Centrum St. Radboud - Nijmegen	Nijmegen
Netherlands	Erasmus MC - Daniel den Hoed Cancer Center	Rotterdam
Netherlands	Universitair Medisch Centrum - Academisch Ziekenhuis	Utrecht
Portugal	Hospitais da Universidade de Coimbra (HUC)	Coimbra
Spain	Hospital Universitario San Carlos	Madrid
United Kingdom	NHS Greater Glasgow and Clyde - Beatson West of Scotland Cancer Centre	Glasgow	Scotland
United Kingdom	Mid Kent Oncology Centre	Maidstone, Kent
United Kingdom	Queen Elizabeth The Queen Mother Hospital	Margate	England

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

Austria,  Belgium,  France,  Italy,  Netherlands,  Portugal,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival at 5 years		5 years	No