Prognostic and Predictive Impact of uPA/PAI-1

Study Overview
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Brief Summary
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Chemo-N0 (1993-1998) is the first prospective randomized multicenter trial in N0 BC designed to prospectively evaluate the clinical utility of a biomarker. It used uPA/PAI 1 as stratification criteria and randomized high-risk patients to chemotherapy versus observation; low-risk patients remained without any systemic therapy. The trial was designed to answer two principle questions: Can the reported prognostic impact of uPA and PAI 1 be validated in a prospective multicenter therapy trial? Does low uPA/PAI 1 identify those low-risk N0 patients who are candidates for being spared necessity and burden of adjuvant chemotherapy? Do uPA/PAI 1 high-risk patients benefit from adjuvant CMF chemotherapy?

Official Title
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Adjuvant Chemotherapy in Node-negative Breast Cancer: Chemo N0

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: CMF Chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: N0 breast cancer patients tumor size >/= 1 and </= 5 cm in diameter undergoing standard loco-regional treatment Exclusion Criteria: M1 status

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Diagnostic
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: A<br>Low uPA/PAI-1: Observation | |
| No Intervention: B2<br>High uPA/PAI-1: Observation | |
| No Intervention: B3<br>High uPA/PAI-1: refused randomization | |
| Active Comparator: B1<br>High uPA/PAi-1: CMF chemotherapy | Drug: CMF Chemotherapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prognostic impact of uPA/PAI-1: Number of patients disease-free in low vs. high risk groups according to uPA/PAI-1 | Interim analyses planned at 4.5, 6.5, and 8.5 years after first patient in. Final analysis scheduled at 10.5 years after last patient in. | DFS at 3, 5, and 10 years (depending on analysis time point) | 
| The benefit of adjuvant chemotherapy in high-risk group according to uPA/PAI-1: Number of patients disease-free vs. those relapsed at the given time points | Interim analyses planned at 4.5, 6.5, and 8.5 years after first patient in. Final analysis scheduled at 10.5 years after last patient in. | DFS at 3, 5, and 10 years (depending on analysis time point) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Interim analyses planned at 4.5, 6.5, and 8.5 years after first patient in. Final analysis scheduled at 10.5 years after last patient in. | at 3, 5, and 10 years (depending on analysis time point). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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node-negative