PiA: Prognosis Used Every Day for Patients With Operable Breast Cancer - Comparison of Invasion Factors uPA/PAI-1 With Other Prognostic Factors

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Eva Johanna Kantelhardt, Martin-Luther-Universität Halle-Wittenberg
ClinicalTrials.gov Identifier:
NCT01592825
First received: May 3, 2012
Last updated: June 28, 2012
Last verified: June 2012

May 3, 2012
June 28, 2012
September 2009
May 2011   (final data collection date for primary outcome measure)
Event free survival [ Time Frame: 2.5 years minimum observation time ] [ Designated as safety issue: No ]
All patients will be followed after a minimum observation time of 2.5 years.
Not Provided
Complete list of historical versions of study NCT01592825 on ClinicalTrials.gov Archive Site
Overall survival [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]
All patients will be followed after a minimum observation time of 2.5 years
Not Provided
Not Provided
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PiA: Prognosis Used Every Day for Patients With Operable Breast Cancer - Comparison of Invasion Factors uPA/PAI-1 With Other Prognostic Factors
PiA Trial: a Cross-sectional, Multicenter, Consecutive Cohort Evaluating the Distribution of uPA/PAI-1 Versus St. Gallen Algorithm in >1000 Prospectively Included Patients

The improvement of the healing rates for breast cancer is based to an important part on the consistent use of so-called adjuvant ("supporting ") medicamentous therapies, including chemotherapy. However this success has a price due to still inaccurate knowledge of the individual risk of relapse: a high number of unnecessary therapies are applied (over-therapy!). The invasion factors uPA (plasminogen activator of the urokinase type) and PAI-1 (uPA inhibitor) were described extensively as strong and independent prognosis factors with high clinical relevance for patients with node negative breast cancer. Compared to clinical and pathological factors (further: "traditional factors ") they show better estimation of the relapse risk leading to an avoidance of redundant adjuvant chemotherapy and may thus essentially contribute to the improvement of the quality of life in these women. In this study we aim to evaluate, how large the portion of the patients with early, operable, node negative breast cancer will be, in whom, by improved low-risk identification through uPA/PAI-1, adjuvant chemotherapy can be omitted.

The determination of the prognostic factors uPA/PAI-1 (further: "biological") is established and recommend by recent guidelines. However, so far data can only show their independent and strong prognostic influence. The absolute proportion of patients, which profit from the improved risk assessment, is only estimated from old trials with different patient populations.

Depending upon assessment, the proportion of low risk patients by traditional risk assessment is 20 - 40%, by biological assessment 35 - 55% of all node negative patients. The data from investigations of historic populations are not reproducible now because of smaller tumor size at presentation due to diagnostic procedures (Screening, good public promotion).

The effectiveness and clinical relevance of the risk assessment were already confirmed for the biological prognostic factors uPA/PAI-1 in node negative breast cancer in several retrospective and prospective trials as well as in a meta-analysis. Still these biological factors (or others!) are not yet established into nationwide clinical routine in Germany. This is due to higher expenditure of this method for the primary therapy (uPA/PAI-1 is determined in the shock-frozen tissue), on the other hand due to the absence of reimbursement. Therefore presently in many centres risk estimation and associated therapy decision is done by traditional assessment.

In order to justify the higher expenditure and the additional costs by the uPA/PAI-1-determination, not only the clear proof of the advantage for the individual patient, but also the estimation of the extent of this advantage in all applicable patients is necessary.

A first goal of this project is to compare the respective proportion of patients allocated as high- or low-risk by means of biological and also traditional prognosis factors in a defined consecutive patient cohort. The determination of uPA/PAI-1 should be established as standard procedure in the future.

So far, the question discussed above referred mainly to patients with node negative breast cancer. In this group, the largest effect in saving chemotherapy is to be expected. Due to previous results we assume that also in node positive patients adjuvant chemotherapy may be saved in sub-group because of very small risk of recurrence. Therefore the determination of uPA/PAI-1 for this group of patients will also be done at the end of this study.

A second goal of this project is it to collect data for risk assessment in node positive patients to be able to offer assistance in the future to perhaps give a better estimation of the individual risk of recurrence.

Practically fresh frozen tissue will be taken, shock-frozen and stored from all consecutive patients operated in the five participating hospitals. The determination of uPA/PAI-1 will be performed in the research laboratory of department of Gynaecology at the University Hospital in Halle (Saale).

A third goal is it to provide biological risk assessment by giving results of uPA/PAI-1 testing promptly to participating node negative patients. This information will be crucial in their decision for or against chemotherapy.

Amendment 2 from June 12, 2012 (Steering committee E Kantelhardt, M Vetter, Ch Thomssen)

A) Established prognostic factors (RNA level) will be evaluated in the context of uPA/PAI-1 and immunohistochemistry markers on samples from the frozen and FFPE tissue. The list of genes is submitted to the Ethics sommittee.

B) Eplorative analysis of these factors concerning response to therapy will be done.

C) Follow-up information will be collected after a minimum observation time of 2.5 years for all patients (in October 2013).

Observational
Observational Model: Cohort
Time Perspective: Prospective
Not Provided
Retention:   Samples With DNA
Description:

Tumor specimen frozen Tumor specimen formalin fixed

Non-Probability Sample

Patients with newly diagnosed, operable breast cancer without metastasis.

Breast Cancer
Not Provided
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
1000
September 2012
May 2011   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • newly diagnosed breast cancer
  • no metastasis detected
  • operation for breast cancer
  • female patient
  • unilateral breast cancer
  • informed consent given
  • age min. 18 yrs.

Exclusion Criteria:

  • metastasis of breast cancer
  • bilateral breast cancer
  • other cancer within the last 5yrs
Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT01592825
GYN_Halle_01
No
Eva Johanna Kantelhardt, Martin-Luther-Universität Halle-Wittenberg
Martin-Luther-Universität Halle-Wittenberg
Not Provided
Principal Investigator: Eva J Kantelhardt, MD Gynecology Martin Luther Univ Halle/Germany
Martin-Luther-Universität Halle-Wittenberg
June 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP