Clinical trial NCT00005583: Radiation Therapy With or Without Chemotherapy in Treating Patients With High-Risk Endometrial Cancer
Official title: A Randomized Trial of Adjuvant Treatment With Radiation Plus Chemotherapy Versus Radiation Alone in High Risk Endometrial Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Endometrial Cancer
Keywords: stage I endometrial carcinoma
stage II endometrial carcinoma
endometrial adenocarcinoma
endometrial papillary serous carcinoma
endometrial clear cell carcinoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: European Organisation for Research and Treatment of Cancer - EORTC
First posted: 2003-01-27
Enrollment: 400
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether radiation therapy with chemotherapy is more effective than radiation therapy alone in treating high-risk endometrial cancer.

PURPOSE: This randomized phase III trial is studying radiation therapy and chemotherapy to see how well they work compared to radiation therapy alone in treating patients with high-risk endometrial cancer.

Detailed description: OBJECTIVES:

* Compare relapse-free survival of patients with high-risk endometrial carcinoma treated in the adjuvant setting with either radiotherapy alone or radiotherapy and chemotherapy given sequentially.
* Compare overall survival of this patient population treated with these 2 adjuvant regimens.
* Evaluate the addition of chemotherapy to standard adjuvant radiotherapy, in terms of toxicity, in these patients.
* Study whether the pattern of relapse in these patients is influenced by the addition of chemotherapy to adjuvant radiotherapy.

OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to center and histologic type (serous papillary and clear cell vs all other types). Patients are randomized to 1 of 2 treatment arms.

All patients undergo hysterectomy with bilateral salpingooophorectomy and extirpation of macroscopic suspicious lymph nodes.

* Arm I: Within 7 weeks after surgery, patients begin radiotherapy.
* Arm II: Patients receive radiotherapy followed by or preceded by chemotherapy\*. Patients receive cisplatin IV over 60 minutes and doxorubicin or epirubicin IV over 10-20 minutes on day 1. Treament repeats every 21 days for 4 courses.

NOTE: \*If radiotherapy is preceded by chemotherapy, radiotherapy begins within 4 weeks after chemotherapy.

Patients are followed at 3 and 6 months and then every 6 months for 5 years.

PROJECTED ACCRUAL: A total of 400 patients (200 per treatment arm) will be accrued for this study within 5 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed endometrial cancer of 1 of the following types:

  * Clear cell carcinoma
  * Serous papillary carcinoma
  * Undifferentiated (anaplastic) carcinoma
  * Poorly differentiated (FIGO grade 3) adenocarcinoma with infiltration to more than half the myometrial thickness
* No small cell carcinoma with neuroendocrine differentiation
* Primary in FIGO surgical stage I or occult stage II
* No spread of disease outside the uterine corpus except to pelvic lymph nodes

  * No spread of disease to para-aortic lymph nodes
* Positive peritoneal washings allowed
* No preoperative macroscopic tumor involvement of the cervix

  * Microscopic tumor involvement of the cervix on histopathological evaluation of the operative uterine specimen allowed

PATIENT CHARACTERISTICS:

Age:

* Any age

Performance status:

* WHO 0-2

Life expectancy:

* Not specified

Hematopoietic:

* Adequate bone marrow function
* WBC at least 3,500/mm\^3
* Platelet count at least 100,000/mm\^3

Hepatic:

* Adequate hepatic function

Renal:

* Adequate renal function
* Creatinine no greater than 1.4 mg/dL

Pulmonary:

* Adequate pulmonary function

Other:

* Not pregnant or nursing
* Fit to receive combination chemotherapy
* No other malignancy except basal cell or squamous cell skin cancer
* No uncontrolled or potentially active site of infection (e.g., fistula or abscesses)
* No other concurrent condition that would produce a substantial increase in risk for complications from radiotherapy
* No other concurrent condition that would interfere with adequate follow-up

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* Not specified

Endocrine therapy:

* Not specified

Radiotherapy:

* No prior preoperative irradiation

Surgery:

* No prior extensive abdominal surgery

Primary outcomes:
measure: Progression-free survival
measure: Relapse-free survival
Secondary outcomes:
measure: Overall survival
Other outcomes:
Locations:
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: Rouen
country: France
facility: Centre Henri Becquerel
city: Dublin
country: Ireland
facility: Coombe Women's Hospital
city: Dublin
country: Ireland
facility: St. James's Hospital
city: Naples
country: Italy
facility: Istituto Nazionale per lo Studio e la Cura dei Tumori
city: Parma
country: Italy
facility: Azienda Ospedaliera Di Parma
city: Pavia
country: Italy
facility: Fondazione I.R.C.C.S. Policlinico San Matteo
city: Varese
country: Italy
facility: Ospedale di Circolo e Fondazione Macchi
city: Amsterdam
country: Netherlands
facility: Onze Lieve Vrouwe Gasthuis
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
city: Nijmegen
country: Netherlands
facility: Universitair Medisch Centrum St. Radboud - Nijmegen
city: Oslo
country: Norway
facility: Norwegian Radium Hospital
city: Gdansk
country: Poland
facility: Medical University of Gdansk
city: Coimbra
country: Portugal
facility: Hospitais da Universidade de Coimbra (HUC)
city: Cape Town
country: South Africa
facility: Groote Schuur Hospital
city: Madrid
country: Spain
facility: Hospital Universitario San Carlos
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital NHS Trust
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: Norwegian Radium Hospital
name: Gunnar B. Kristensen, MD, PhD
role: STUDY_CHAIR
affiliation: Hospitais da Universidade de Coimbra (HUC)
name: Carlos F. de Oliveira, MD, PhD
References:
citation: Hogberg T, Signorelli M, de Oliveira CF, Fossati R, Lissoni AA, Sorbe B, Andersson H, Grenman S, Lundgren C, Rosenberg P, Boman K, Tholander B, Scambia G, Reed N, Cormio G, Tognon G, Clarke J, Sawicki T, Zola P, Kristensen G. Sequential adjuvant chemotherapy and radiotherapy in endometrial cancer--results from two randomised studies. Eur J Cancer. 2010 Sep;46(13):2422-31. doi: 10.1016/j.ejca.2010.06.002. Epub 2010 Jul 7.
citation: Hogberg T, Rosenberg P, Kristensen G, et al.: A randomized phase-III study on adjuvant treatment with radiation (RT) ± chemotherapy (CT) in early-stage high-risk endometrial cancer (NSGO-EC-9501/EORTC 55991). [Abstract] J Clin Oncol 25 (Suppl 18): A-5503, 274s, 2007.