Cetuximab and Cisplatin in Treating Patients With Advanced, Persistent, or Recurrent Cervical Cancer

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Cetuximab may also help cisplatin work better by making tumor cells more sensitive to the drug. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving cetuximab together with cisplatin may be a better way to block tumor growth. PURPOSE: This phase II trial is studying how well giving cetuximab together with cisplatin works in treating patients with advanced, persistent, or recurrent cervical cancer.

Detailed Description
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OBJECTIVES: Primary Determine the antitumor activity of cetuximab and cisplatin, in terms of objective tumor response (partial and complete), in patients with advanced, persistent, or recurrent carcinoma of the cervix. Determine the nature and degree of toxicity of this regimen in these patients. Secondary Determine the progression-free survival and overall survival of patients treated with this regimen. Correlate epidermal growth factor receptor expression with progression-free survival, overall survival, and response in patients treated with this regimen. OUTLINE: This is a multicenter study. Patients receive cetuximab IV over 1-2 hours on days 1, 8, and 15 and cisplatin IV on days 1 and 8. Courses repeat every 21 days in the absence of unacceptable toxicity or disease progression. Patients are followed every 3 months for 2 years and then every 6 months for 3 years. PROJECTED ACCRUAL: A total of 28-62 patients will be accrued for this study within 9-20 months.

Official Title
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A Limited Access Phase II Trial of Cetuximab (C225, NSC #714692) in Combination With Cisplatin (NSC #119875) in the Treatment of Advanced, Persistent, or Recurrent Carcinoma of the Cervix

Conditions
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Cervical Cancer

Intervention / Treatment
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* Biological: cetuximab
* Drug: cisplatin


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed squamous or non-squamous cell carcinoma of the cervix Advanced, persistent, or recurrent disease Documented disease progression Not amenable to curative therapy Measurable disease At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan At least 1 target lesion Tumors within a previously irradiated field are designated as non-target lesions unless progression is documented or a biopsy is obtained ≥ 90 days after completion of radiotherapy to confirm persistence PATIENT CHARACTERISTICS: Age 18 and over Performance status GOG 0-2 Life expectancy Not specified Hematopoietic Platelet count ≥ 100,000/mm^3 Absolute neutrophil count ≥ 1,500/mm^3 Hepatic Bilirubin ≤ 1.5 times upper limit of normal (ULN) AST ≤ 2.5 times ULN Alkaline phosphatase ≤ 2.5 times ULN Renal Creatinine ≤ 1.5 times ULN Cardiovascular No significant history of cardiac disease within the past 6 months, including the following: Unstable angina Uncontrolled hypertension Uncontrolled congestive heart failure Uncontrolled arrhythmia Neurologic No uncontrolled seizure disorder No active neurological disease No neuropathy (sensory and motor) > grade 1 Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No active infection requiring antibiotics No other invasive malignancy within the past 5 years except nonmelanoma skin cancer PRIOR CONCURRENT THERAPY: Biologic therapy No prior anti-epidermal growth factor receptor (EGFR) antibody therapy No prior chimerized or murine monoclonal antibody therapy Chemotherapy Not specified Endocrine therapy At least 1 week since prior anticancer hormonal therapy Concurrent hormone replacement therapy allowed Radiotherapy See Disease Characteristics At least 4 weeks since prior radiotherapy Surgery More than 30 days since prior major surgery, except diagnostic biopsy Other Recovered from all prior therapy No prior cytotoxic therapy for cervical cancer No prior tyrosine kinase inhibitor therapy that targets the EGFR pathway No prior cancer treatment that would contraindicate study therapy No other concurrent investigational agents

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: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: cetuximab|nan|
|Drug: cisplatin|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor Response | Per GOG Response Evaluation Criteria In Solid Tumors(RECIST) Criteria: Complete Response(CR): disappearance of all target and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial Response(PR): at least a 30% decrease in the sum of longest dimensions(LD) of all target measurable lesions taking as reference the baseline sum of LD. There can be no unequivocal progression of nontarget lesions and no new lesions. Increasing Disease: at least a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD or the appearance of new lesions within 8 weeks of study entry. Stable Disease: any condition not meeting the above criteria. Indeterminate for response: as having no repeat tumor assessments following initiation of study therapy for reasons unrelated to symptoms or signs of disease. | up to 6 months from study entry | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival and Overall Survival at 6 Months After Completion of Treatment |  | up to 5 years from study entry | 

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