Epoetin Beta in Treating Anemia in Patients With Cervical Cancer

Study Overview
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Brief Summary
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RATIONALE: Epoetin beta may stimulate red blood cell production to prevent or control anemia in patients treated with chemotherapy and radiation therapy. PURPOSE: Randomized phase IV trial to determine the effectiveness of epoetin beta in treating anemia in patients who are receiving cisplatin and radiation therapy for stage IIB, stage III, or stage IVA cervical cancer.

Detailed Description
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OBJECTIVES: Compare the effectiveness of epoetin beta vs standard care for anemia management, in terms of increased hemoglobin levels and the correlation with reduced relapse/treatment failure rate, in patients with stage IIB, III, or IVA cervical cancer treated with cisplatin and radiotherapy. Compare the safety of these regimens in these patients. Compare the relapse-free and overall survival of patients treated with these regimens. Compare the frequency and localization of relapses and metastases in patients treated with these regimens. Compare the quality of life of patients treated with these regimens. Compare the type, frequency, and degree of adverse events in patients treated with these regimens. Compare the overall response rate in patients treated with these regimens. OUTLINE: This is a randomized, open-label, parallel-group, multicenter study. Patients are stratified according to country, disease stage, and brachytherapy technique. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients undergo radiotherapy 5 days a week for 6 weeks. Patients also undergo high-dose rate, low-dose rate, or boost brachytherapy. Patients receive cisplatin IV beginning on day 1 of radiotherapy and continuing weekly for 6 weeks. Patients also receive epoetin beta subcutaneously 3 times a week beginning 2 weeks before radiotherapy and continuing for 8 weeks. Arm II: Patients undergo radiotherapy and brachytherapy and receive cisplatin as in arm I. Quality of life is assessed at baseline, after the last treatment, and at 3 months. Patients are followed every 3 months for 2 years and then every 6 months thereafter. PROJECTED ACCRUAL: A total of 80-450 patients will be accrued for this study within 4-22.5 months.

Official Title
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Management Of Anemia Under RadioChemotherapy (MARCH): An Open, Randomized Multicenter Study Of The Effect Of NeoRecormon On Treatment Outcome In Patients With Advanced Cervical Cancer Stage IIB -IVA Treated With Primary Simultaneous Radiochemotherapy (Radiotherapy Plus Cisplatin)

Conditions
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Anemia, Cervical Cancer

Intervention / Treatment
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* Biological: epoetin beta
* Drug: cisplatin
* Radiation: brachytherapy
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed stage IIB, III, or IVA cervical cancer No chorion carcinoma or neuroendocrine small cell carcinoma Previously untreated disease Must be scheduled to undergo radiotherapy and receive cisplatin as primary therapy Hemoglobin 8.0-13.0 g/dL No relevant acute bleeding within the past 3 months, including anemia caused by gross bleeding from tumor No distant metastasis No positive para-aortic lymph nodes PATIENT CHARACTERISTICS: Age Over 18 Performance status WHO 0-2 Life expectancy At least 3 months Hematopoietic See Disease Characteristics WBC greater than 3,000/mm3 Platelet count greater than 100,000/mm3 No hemolytic anemia No transferrin saturation less than 20% that cannot be treated with IV iron No hemoglobinopathies (i.e., sickle cell disease or thalassemia of all types) Hepatic Bilirubin no greater than 1.5 times upper limit of normal (ULN) Transaminases no greater than 2.5 times ULN Alkaline phosphatase no greater than 2.5 times ULN Renal Creatinine clearance greater than 60 mL/min Cardiovascular No chronic heart failure No New York Heart Association class II-IV heart disease No uncontrolled arterial hypertension (systolic blood pressure at least 170 mmHg, diastolic blood pressure at least 100 mmHg) No prior deep vein thrombosis No thrombocytosis Other No vitamin B12 deficiency No folic acid deficiency No newly diagnosed (unstable) epilepsy No acute infection No other malignancy within the past 5 years except basal cell carcinoma in situ No known peripheral neuropathy or moto-sensory neurotoxicity grade 2 or greater No impaired hearing grade 2 or greater No hypersensitivity to benzyl alcohol, benzoic acid, benzalkonium chloride, or any excipients of cisplatin preparations Not pregnant or nursing PRIOR CONCURRENT THERAPY: Biologic therapy At least 3 months since prior epoetins or related compounds Chemotherapy See Disease Characteristics Endocrine therapy Not specified Radiotherapy See Disease Characteristics No prior radiotherapy for cervical cancer Surgery Not specified Other At least 30 days since prior investigational drugs No prior systemic antineoplastic therapy for cervical cancer No other concurrent investigational drugs

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: epoetin beta|nan|
|Drug: cisplatin|nan|
|Radiation: brachytherapy|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of treatment failures within 6 months after beginning radiochemotherapy (RCT) (stage I) |  |  | 
| Overall survival after RCT (stage II) |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression/relapse-free survival |  |  | 
| Overall response rate to RCT |  |  | 
| Overall survival after RCT (stage I) |  |  | 
| Frequency and localization of relapses and/or metastases |  |  | 
| Change in hemoglobin from baseline during therapy |  |  | 
| Quality of life as assessed by the Functional Assessment of Cancer Therapy-Anemia |  |  | 
| Type, frequency, and degree of adverse events |  |  | 
| Safety |  |  | 
| Vital signs |  |  | 
| Number of treatment failures within 6 months after beginning RCT (stage II) |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anemia, stage IIB cervical cancer, stage III cervical cancer, stage IVA cervical cancer, cervical adenosquamous cell carcinoma, cervical squamous cell carcinoma, cervical adenocarcinoma