Last updated on February 2019

The p53 Breast Cancer Trial


Brief description of study

This is a multicenter, open labeled, phase 2 clinical trial, where patients are stratified to one of two treatment groups based on upfront TP53 mutation status; i.e. TP53 mutated vs. TP53 wt disease, and treated with dose-dense cyclphosphamide. Furthermore, patients included are stratified based on tumor stage; i.e. locally advanced breast cancer (M0 disease) or metastatic breast cancer (M1 disease). All participating cancer centers will prospectively include patients with breast cancer fulfilling the inclusion criteria.

If patients do not respond to the experimental treatment as outlined in the protocol, treatment with dose-dense cyclophosphamide will be terminated, and further cancer treatment will continue at the treating oncologist's discretion. The response data for all patients who have received at least one chemotherapy course will be included in the final efficacy analysis.

Tumor tissue, blood samples and radiology data will be collected before therapy starts, if therapy needs to be changed, and for patients with locally advanced breast cancer: at surgery. Response data will be evaluated closely during treatment, with clinical assessment of tumor size every two weeks for patients with locally advanced breast cancer and by radiology every eight weeks for patients with metastatic breast cancer. Evaluation of side effects/tolerance will be performed at every clinical visit, i.e. every two weeks for all patients included in the p53 trial.

Detailed Study Description

Stage IV breast cancer (distant metastases) remains a non-curable condition; thus, treatment is considered palliative. However, many patients may live for years with their metastatic disease with a reasonably good quality of life. As for locally advanced primary breast cancers in need of primary medical therapy, lack of responsiveness to regular chemotherapy is associated with a poor prognosis, with a high risk of relapse and, subsequent, breast cancer death. TP53 mutations have been shown to predict a poor response to anthracyclines, a group of cytotoxic agents which is extensively used and which is in general efficacious in breast cancer. Notably, dose-intensification with cyclophosphamide has been found to significantly improve the response rate in TP53 mutated primary breast cancers. Our preliminary experience indicates that the use of dose-dense cyclophosphamide monotherapy every 2nd week with G-CSF support is well tolerated. As for patients with metastatic disease for whom the alternative would be to receive continuous chemotherapy at 3-weekly intervals the hypothesis is that cyclophosphamide given at 2-weekly intervals over a limited time period, followed by a "treatment holiday" among responders should be associated with a non-inferior quality of life all-over. As for patients with TP53 mutated locally advanced breast cancers where standard chemotherapy fails, the hypothesis is that cyclophosphamide dose dense treatment may be an effective treatment option downstaging the tumor prior to surgery.

Clinical Study Identifier: NCT02965950

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