Clinical trial NCT00052312: Doxorubicin and Cisplatin With or Without Paclitaxel in Treating Patients With Locally Advanced, Metastatic, and/or Relapsed Endometrial Cancer
Official title: Randomized Trial Of Adriamycin (A) Cisplatin (P) Chemotherapy Versus Paclitaxel (T) Adriamycin (A) And Cisplatin (P) In Patients With Metastatic/Relapsed Or Locally Advanced Inoperable Endometrial Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Endometrial Cancer
Keywords: recurrent endometrial carcinoma
stage III endometrial carcinoma
stage IV endometrial carcinoma
endometrial papillary serous carcinoma
Lead sponsor: European Organisation for Research and Treatment of Cancer - EORTC
Sponsor class: NETWORK
First posted: 2003-01-27
Enrollment: 141
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known whether doxorubicin and cisplatin are more effective with or without paclitaxel in treating endometrial cancer.

PURPOSE: Randomized phase II trial to compare the effectiveness of combining doxorubicin and cisplatin with or without paclitaxel in treating patients who have locally advanced, metastatic, and/or relapsed endometrial cancer.

Detailed description: OBJECTIVES:

* Compare the overall survival of patients with locally advanced, metastatic, and/or relapsed endometrial cancer treated with doxorubicin and cisplatin with or without paclitaxel.
* Compare the toxicity of these regimens in these patients.
* Compare the progression-free survival at 18 months of patients treated with these regimens.
* Compare quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to performance status (0 vs 1 vs 2), metastatic disease (M0 vs M1), prior pelvic radiotherapy for pelvic recurrence (yes vs no), and participating center. Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive doxorubicin IV over 30 minutes, paclitaxel IV over 3 hours, and cisplatin IV over 1 hour on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
* Arm II: Patients receive doxorubicin and cisplatin as in arm I. Quality of life is assessed at baseline, before each course, after courses 3 and 6, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter. In the event of progressive disease, quality of life is assessed every 3 months.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter. In the event of progressive disease, patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 140 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed endometrial epithelial carcinoma meeting at least 1 of the following criteria:

  * Advanced metastatic and/or relapsed disease
  * Locally advanced inoperable or unresectable disease
* No mixed mesodermal tumor and/or tumors showing evidence of sarcomatous elements
* Uterine papillary serous carcinoma allowed

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* WHO 0-2

Life expectancy

* Not specified

Hematopoietic

* Neutrophil count greater than 1,500/mm\^3
* Platelet count at least 100,000/mm\^3
* Hemoglobin greater than 10 g/dL (transfusions allowed)

Hepatic

* ALT and AST less than 2 times upper limit of normal (ULN)
* Alkaline phosphatase less than 2 times ULN
* Bilirubin less than 1.5 times ULN

Renal

* Creatinine less than 1.5 times ULN
* Creatinine clearance greater than 50 mL/min

Cardiovascular

* Normal baseline EKG
* Normal baseline LVEF on MUGA or echocardiogram for patients who received prior anthracyclines

Other

* Able to tolerate high-dose dexamethasone
* Must be considered fit for chemotherapy
* No uncontrolled infection
* No other malignancy within the past 5 years except successfully treated basal cell skin cancer or carcinoma in situ of the cervix
* No prior nervous or psychiatric disorder that would preclude study compliance
* No psychological, familial, sociological, or geographic condition that would preclude study participation
* Not pregnant or nursing
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

* Not specified

Chemotherapy

* At least 12 months since prior adjuvant chemotherapy
* Total dose of prior doxorubicin no greater than 200 mg/m\^2
* Total dose of prior epirubicin no greater than 300 mg/m\^2

Endocrine therapy

* At least 28 days since prior hormonal therapy for patients with partial or complete response after first-line treatment

Radiotherapy

* No prior radiotherapy to any area other than pelvis
* No concurrent radiotherapy

Surgery

* Not specified

Other

* No other concurrent anticancer medications

Primary outcomes:
measure: Progression-free survival as measured by Kaplan Meier and RECIST at 18 months
Secondary outcomes:
measure: Overall survival as measured by Kaplan Meier after each course, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter
measure: Toxicity as measured by NCIC Common Toxicity Criteria v2.0 after each course
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Allgemeines Krankenhaus - Universitatskliniken
city: Antwerp
country: Belgium
facility: Ziekenhuis Netwerk Antwerpen Middelheim
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Kortrijk
country: Belgium
facility: Cazk Groeninghe - Campus Maria's Voorzienigheid
city: Leuven
country: Belgium
facility: U.Z. Gasthuisberg
city: Wilrijk
country: Belgium
facility: Algemeen Ziekenhuis Sint-Augustinus
city: Caen
country: France
facility: Centre Regional Francois Baclesse
city: Lyon
country: France
facility: Centre Leon Berard
city: Aviano
country: Italy
facility: Centro di Riferimento Oncologico - Aviano
city: Pavia
country: Italy
facility: I.R.C.C.S. Policlinico San Matteo
city: Turin
country: Italy
facility: Azienda Sanitaria Ospedaliera Ordine Mauriziano
city: Turin
country: Italy
facility: Clinica Universitaria
city: Voghera
country: Italy
facility: Ospedale Civile
city: Amsterdam
country: Netherlands
facility: Onze Lieve Vrouwe Gasthuis
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum at University of Amsterdam
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Nijmegen
country: Netherlands
facility: Universitair Medisch Centrum St. Radboud - Nijmegen
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
city: Coimbra
country: Portugal
facility: Hospitais da Universidade de Coimbra (HUC)
city: Madrid
country: Spain
facility: Hospital Universitario San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Valencia
country: Spain
facility: Instituto Valenciano De Oncologia
city: Bath
country: United Kingdom
facility: Royal United Hospital
state: England
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
state: England
city: Leeds
country: United Kingdom
facility: Leeds Cancer Centre at St. James's University Hospital
state: England
city: Merseyside
country: United Kingdom
facility: Clatterbridge Centre for Oncology NHS Trust
state: England
city: Middlesbrough
country: United Kingdom
facility: James Cook University Hospital
state: England
city: Newcastle-Upon-Tyne
country: United Kingdom
facility: Northern Centre for Cancer Treatment at Newcastle General Hospital
state: England
city: Northwood
country: United Kingdom
facility: Mount Vernon Cancer Centre at Mount Vernon Hospital
state: England
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital NHS Trust
state: England
city: Romford
country: United Kingdom
facility: Oldchurch Hospital
state: England
city: Belfast
country: United Kingdom
facility: Centre for Cancer Research and Cell Biology at Belfast City Hospital
state: Northern Ireland
city: Glasgow
country: United Kingdom
facility: Western Infirmary
state: Scotland
Study officials:
affiliation: University of Glasgow
name: Nicholas S. Reed, MD
role: STUDY_CHAIR
affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
name: Giorgio Bolis, MD
role: STUDY_CHAIR
References: