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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier:
NCT00039338
First received: June 6, 2002
Last updated: July 2, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Cervical Cancer
Procedure: conventional surgery
Procedure: neoadjuvant chemotherapy
Radiation: brachytherapy
Radiation: radiation therapy
Drug: cisplatin
Phase 3

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

Resource links provided by NLM:


Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Primary Outcome Measures:
  • Overall survival as measured by Kaplan Meier after each course, every 3 months for 1 year, every 6 months for 4 years, and then annually [ Time Frame: 16 years from FPI ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival as measured by Kaplan Meier and RECIST after each course, every 3 months for 1 year, every 6 months for 4 years, and then annually [ Time Frame: 16 years from FPI ] [ Designated as safety issue: No ]
  • Toxicity as measured by NCIC Common Toxicity Criteria v2.0 after each course [ Time Frame: 16 years from FPI ] [ Designated as safety issue: Yes ]
  • Health-related quality of life as measured by Quality of Life Questionnaire-C30 at baseline and at 6, 12, 18, and 24 months [ Time Frame: 16 years from FPI ] [ Designated as safety issue: No ]

Estimated Enrollment: 686
Study Start Date: March 2002
Estimated Study Completion Date: April 2018
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Chemotherapy followed by surgery
neoadjuvant chemotherapy (Cisplatin) followed by surgery (radial hysterectomy)
Procedure: conventional surgery
Radial hysterectomy
Procedure: neoadjuvant chemotherapy
Experimental arm: minimal cumulative cisplatin dose of 225 mg/m2. Comparator arm: cumulative cisplatin dose of 200-240 mg/m2.
Drug: cisplatin
Minimal cumulative 225 mg/m2 (experimental arm). Cumulative 200-240 mg/m2 (comparator arm).
Active Comparator: Radio-chemotherapy
Concomitant radiotherapy (external radiotherapy combined with external boost or brachytherapy) and chemotherapy (cisplatin)
Procedure: 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: 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).

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00039338

Locations
Austria
Karl-Franzens-University Graz
Graz, Austria
Kaiser Franz Josef Hospital
Vienna, Austria
Belgium
Universitair Ziekenhuis Antwerpen
Edegem, Belgium
U.Z. Gasthuisberg
Leuven, Belgium
Centre Hospitalier Regional de la Citadelle
Liege, Belgium, 4000
France
Centre Regional Francois Baclesse
Caen, France
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, 10128
Clinica Universitaria
Turin, Italy, 10126
Ospedale di Circolo e Fondazione Macchi
Varese, Italy
Netherlands
Academisch Medisch Centrum at University of Amsterdam
Amsterdam, Netherlands, 1105 AZ
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, 3008 AE
Universitair Medisch Centrum - Academisch Ziekenhuis
Utrecht, Netherlands
Portugal
Hospitais da Universidade de Coimbra (HUC)
Coimbra, Portugal
Spain
Hospital Universitario San Carlos
Madrid, Spain
United Kingdom
Queen Elizabeth The Queen Mother Hospital
Margate, England, 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
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Investigators
Study Chair: Fabio Landoni, MD Istituto Europeo Di Oncologia, Milano
Study Chair: Alessandro Colombo, MD Ospedale Alessandro Manzoni, Lecco
Study Chair: Stefano Greggi, MD, PhD Istituto Nazionale per lo Studio e la Cura dei Tumori, Napoli
Study Chair: Gemma G. Kenter, MD Academisch Medisch Centrum - Universiteit van Amsterdam
  More Information

Additional Information:
No publications provided

Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT00039338     History of Changes
Other Study ID Numbers: EORTC-55994, 2008-003396-52
Study First Received: June 6, 2002
Last Updated: July 2, 2014
Health Authority: Austria: Agency for Health and Food Safety
Belgium: Federal Agency for Medicinal Products and Health Products
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Italy: AIFA: Italian Drug Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Portugal: National Authority of Medicines and Health Products
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
stage IB cervical cancer
stage IIB cervical cancer
stage IIA cervical cancer
cervical squamous cell carcinoma
cervical adenocarcinoma
cervical adenosquamous cell carcinoma

Additional relevant MeSH terms:
Uterine Cervical Neoplasms
Genital Diseases, Female
Genital Neoplasms, Female
Neoplasms
Neoplasms by Site
Urogenital Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Uterine Neoplasms
Cisplatin
Antineoplastic Agents
Pharmacologic Actions
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014