Study of Adding Cetuximab to Chemotherapy for the Treatment of Advanced and/or Recurrent Cervical Cancer

Study Overview
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Brief Summary
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This study aims to assess the activity of a combination of cetuximab (weekly) with carboplatin + paclitaxel (every three weeks) comparing it to chemotherapy alone in terms of event-free survival (EFS).

Detailed Description
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The poor long-term results in the standard treatment of chemotherapy for cervical cancer make research into new, more beneficial treatment strategies necessary. Cetuximab is a new type of drug that blocks the epidermal growth factor receptor (anti-EFGR), and has shown significant activity in other cancers (colon, head and neck) where expression of EGFR is high. Cervical cancer cells express EGFR in a very high proportion of cases, especially in recurrent or resistant disease. This study evaluates the activity of the addition of cetuximab to full doses of carboplatin and paclitaxel.

Official Title
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Randomized Phase II Study of Carboplatin and Paclitaxel +/- Cetuximab, in Advanced and/or Recurrent Cervical Cancer

Conditions
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Cervical Cancer

Intervention / Treatment
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* Drug: paclitaxel
* Drug: carboplatin
* Drug: cetuximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Advanced and/or metastatic cervical cancer patients untreated or having failed only one previous chemotherapy (with at least 6 months of progression free interval, with or without concomitant or sequential radiotherapy). At baseline, presence of at least one measurable target lesion (a lesion that can be accurately measured in at least one dimension i.e. longest diameter at least 20 mm with conventional CT scan or at least 10 mm with spiral CT scan according to RECIST Criteria). Not amenable to surgery and/or radiotherapy. PS 0-1 according to ECOG. Age >18. Life expectancy of at least 3 months. Adequate organ functions Hematopoietic: Leukocytes > 3,000/mm3; Absolute neutrophil count > or = 1,500/mm3; Platelets count > or = 100,000/mm3; Hemoglobin > or = 9 g/dL Hepatic: AST and ALT < or = 3 times upper limit of normal (ULN)*; Alkaline phosphatase < or = 3 times ULN*; Bilirubin < or = 1.5 times ULN *: < or = 5 times ULN if liver metastases are present Renal: Creatinine clearance > or = 45 mL/min No other invasive malignancy within the past 5 years except non-melanoma skin cancer. All radiology studies must be performed within 28 days prior to randomization. Absence of any psychological, familial, sociological or geographical conditions potentially hampering compliance with the study protocol and follow-up schedule. Written informed consent. Exclusion Criteria: Pregnant (potentially fertile patients must use contraceptive measures to avoid pregnancy during and for at least 3 months after study participation and must have a negative serum pregnancy test at baseline). Patients should not be breast-feeding during treatment and for 2 months following the end of treatment. More than one previous chemotherapy line. Active infection requiring antibiotics. Symptomatic peripheral neuropathy >grade 2 according to the CTCAE. Congestive heart failure or angina pectoris even if it is medically controlled. Previous history of myocardial infarction within 1 year from study entry, uncontrolled high risk hypertension or arrhythmia. Known hypersensitivity to the study drugs or to drugs with similar chemical structures. Concurrent treatment with other experimental drugs. Participation in another clinical trial with any investigational drug within 30 days prior to study screening.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>chemotherapy plus cetuximab | Drug: paclitaxel<br>* 175 mg/m2 IV day 1, every 21 days<br>Drug: carboplatin<br>* AUC 5 IV day 1 every 21 days<br>Drug: cetuximab<br>* 400 mg/m2 IV, one week before starting carboplatin and paclitaxel; then 250 mg/m2 IV day 1, weekly<br>|
| Active Comparator: Arm B<br>chemotherapy | Drug: paclitaxel<br>* 175 mg/m2 IV day 1, every 21 days<br>Drug: carboplatin<br>* AUC 5 IV day 1 every 21 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| event free survival |  | after 3 and 6 cycles of treatment (each cycle is 21 days), and every 3 months thereafter up to 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| adverse events | according CTCAE criteria | after each treatment cycle (each cycle is 21 days) up to 30days | 
| overall survival |  | 18 months | 
| skin toxicity and correlation with cetuximab activity |  | after 3 and 6 cycles of therapy (each cycle is 21 days), and every 3 months thereafter up to 18 months | 
| EGFR/KRAS expression and correlation with cetuximab activity |  | at 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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EGFR, chemotherapy