Chemotherapy Followed By Surgery Vs Radiotherapy Plus Chemotherapy in Patients With Stage IB or II Cervical Cancer
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
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.
Descripción general del estudio
Estado
Condiciones
Descripción detallada
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.
Tipo de estudio
Inscripción (Anticipado)
Fase
- Fase 3
Contactos y Ubicaciones
Ubicaciones de estudio
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Graz, Austria
- Karl-Franzens-University Graz
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Vienna, Austria
- Kaiser Franz Josef Hospital
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Edegem, Bélgica
- Universitair Ziekenhuis Antwerpen
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Leuven, Bélgica
- U.Z. Gasthuisberg
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Liege, Bélgica, 4000
- Centre Hospitalier Regional de la Citadelle
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Madrid, España
- Hospital Universitario San Carlos
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Caen, Francia
- Centre Regional Francois Baclesse
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Milano, Italia
- Istituto Europeo Di Oncologia
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Monza, Italia
- Ospedale San Gerardo
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Naples, Italia
- Istituto Nazionale per lo Studio e la Cura dei Tumori
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Torino, Italia, 10128
- Ospedale Mauriziano Umberto I
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Turin, Italia, 10126
- Clinica Universitaria
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Varese, Italia
- Ospedale di Circolo e Fondazione Macchi
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Amsterdam, Países Bajos, 1105 AZ
- Academisch Medisch Centrum at University of Amsterdam
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Amsterdam, Países Bajos
- Vrije Universiteit Medisch Centrum
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Enschede, Países Bajos
- Medisch Spectrum Twente
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Leiden, Países Bajos
- Leiden University Medical Center
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Nijmegen, Países Bajos
- Universitair Medisch Centrum St. Radboud - Nijmegen
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Rotterdam, Países Bajos, 3008 AE
- Erasmus MC - Daniel den Hoed Cancer Center
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Utrecht, Países Bajos
- Universitair Medisch Centrum - Academisch Ziekenhuis
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Coimbra, Portugal
- Hospitais da Universidade de Coimbra (HUC)
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Maidstone, Kent, Reino Unido
- Mid Kent Oncology Centre
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England
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Margate, England, Reino Unido
- Queen Elizabeth the Queen Mother Hospital
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Scotland
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Glasgow, Scotland, Reino Unido
- NHS Greater Glasgow and Clyde - Beatson West of Scotland Cancer Centre
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
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
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Experimental: Chemotherapy followed by surgery
neoadjuvant chemotherapy (Cisplatin) followed by surgery (radial hysterectomy)
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Radial hysterectomy
Experimental arm: minimal cumulative cisplatin dose of 225 mg/m2.
Comparator arm: cumulative cisplatin dose of 200-240 mg/m2.
Minimal cumulative 225 mg/m2 (experimental arm).
Cumulative 200-240 mg/m2 (comparator arm).
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Comparador activo: Radio-chemotherapy
Concomitant radiotherapy (external radiotherapy combined with external boost or brachytherapy) and chemotherapy (cisplatin)
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Experimental arm: minimal cumulative cisplatin dose of 225 mg/m2.
Comparator arm: cumulative cisplatin dose of 200-240 mg/m2.
Minimal cumulative 225 mg/m2 (experimental arm).
Cumulative 200-240 mg/m2 (comparator arm).
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.
Between 45-50 Gy, in fractions of 1.8 to 2 Gy.
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Periodo de tiempo |
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Supervivencia global a los 5 años.
Periodo de tiempo: 5 años
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5 años
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Colaboradores e Investigadores
Investigadores
- Silla de estudio: Fabio Landoni, MD, Istituto Europeo Di Oncologia, Milano
- Silla de estudio: Alessandro Colombo, MD, Ospedale Alessandro Manzoni, Lecco
- Silla de estudio: Stefano Greggi, MD, PhD, Istituto Nazionale per lo Studio e la Cura dei Tumori, Napoli
- Silla de estudio: Gemma G. Kenter, MD, Academisch Medisch Centrum - Universiteit van Amsterdam
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (Anticipado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Estimar)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- EORTC-55994
- 2008-003396-52 (Número EudraCT)
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