Cetuximab and Cisplatin in the Treatment of Triple Negative (Estrogen Receptor [ER] Negative, Progesterone Receptor [PgR] Negative, and Human Epidermal Growth Factor Receptor 2 [HER2] Negative) Metastatic Breast Cancer

Study Overview
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Brief Summary
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The primary objective of this study is to determine whether overall response to cetuximab combined with cisplatin is better than overall response to cisplatin alone together with showing that the overall response for cetuximab and cisplatin was above a pre-specified threshold of 0.2 in the treatment of triple negative metastatic breast cancer. The secondary objective of this study is to compare the differences between the two treatment groups using the following criteria : Progression-Free Survival (PFS) Time, Overall Survival (OS), Time to Response (TTR) and Safety.

Official Title
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Randomized Phase II Trial With Cetuximab and Cisplatin in the Treatment of ER-negative, PgR-negative, HER2-negative Metastatic Breast Carcinoma (Basal Like)

Conditions
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Breast Neoplasm

Intervention / Treatment
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* Drug: cetuximab, cisplatin
* Drug: cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed diagnosis of metastatic breast cancer (Stage IV) Estrogen Receptor [ER] negative, PgR negative and HER2 less than 3+ expression by immunohistochemistry (IHC) No more than 1 prior chemotherapy received for treating this metastatic breast cancer No more than 1 prior anthracycline and/or taxane regimen (either adjuvant or metastatic setting) Other protocol-defined inclusion criteria may apply Exclusion Criteria: Prior platinum agent Prior mitomycin Known history of brain metastases Other protocol-defined exclusion criteria may apply

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: cisplatin and cetuximab<br> | Drug: cetuximab, cisplatin<br>* Subjects will receive an initial dose of cetuximab 400 milligram per square meter (mg/m^2) followed by weekly doses of 250 mg/m^2. All doses will be given by intravenous (IV) infusion. Subjects will receive cisplatin (75 mg/m^2 IV on Day 1) every 3 weeks, with a maximum of 6 cycles. Administration of the Investigational Medicinal Product (IMP) will be stopped upon the first occurrence of disease progression, unacceptable toxicity or withdrawal of consent.<br>|
| Active Comparator: cisplatin<br> | Drug: cisplatin<br>* Subjects will receive cisplatin (75 mg/m^2 IV on Day 1) every 3 weeks, with a maximum of 6 cycles. Subjects have the option of receiving cetuximab plus cisplatin at progression within the first 6 cycles, or cetuximab alone at progression after the 6 cycles. Administration of the IMP will be stopped upon the first occurrence of disease progression (except in cisplatin arm where switch to cetuximab plus cisplatin, or cetuximab alone is possible), unacceptable toxicity or withdrawal of consent.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Overall Response (BOR) | Percentage of participants with best overall (objective) response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). | Evaluations were performed every 6 weeks until progression reported between day of first participant randomized, 20 June 2007, until cut-off date, 31 July 2009 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) Time | The PFS was defined as the duration from randomization until radiological progression according to investigator (based on RECIST) or death due to any cause. Only deaths within 85 days of last tumor assessment were considered. Participants without event were censored on the date of last tumor assessment. | Time from randomization to disease progression, death or last tumour assessment, reported between day of first participant randomized, 20 June 2007, until cut-off date, 31 July 2009 | 
| Overall Survival (OS) Time | The OS time was defined as the time from randomization to death. Participants without event were censored at the last date known to be alive or at the clinical cut-off date, whatever was earlier. | Time from randomization to death or last day known to be alive, reported between day of first participant randomized, 20 June 2007, until cut-off date, 05 April 2010 | 
| Time to Response (TTR) | The TTR was determined for participants whose confirmed BOR (based on RECIST) was either a CR or a PR . It was defined as the time from the first dose study treatment until the date of the first assessment of confirmed CR or PR. | Time from the first dose of study treatment (cetuximab or cisplatin) to first assessment of CR or PR, reported between day of first participant randomized, 20 June 2007, until cut-off date, 31 July 2009 | 
| Safety- Number of Participants Experiencing Any Adverse Event (AE) | Number of participants experiencing any AE. AEs: Any untoward medical occurrence in the form of signs, clinically significant abnormalities in laboratory findings, diseases, symptoms, or worsening of complications. | Time from first dose up to 30 days after last dose of study treatment, reported between day of first dose of study treatment, 20 June 2007, until cut-off date 05 April 2010 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cancer, breast, metastatic, triple negative