Clinical Trial: Cardiotoxicity in Metastatic Her 2 Positive Patients Treated With Trastuzumab ,Pertuzumab and Taxanes

Study Status: Recruiting
Recruit Status: Unknown status
Study Type: Observational [Patient Registry]

Official Title: Cardiotoxicity in Metastatic Her 2 Positive Patients Treated With First Line Trastuzumab, Pertuzumab and Taxanes Based Regimen

Brief Summary:

Approximately 15-25% of all breast cancers are human epidermal growth factor receptor 2 (HER2) positive and it has been well known that HER2 overexpression is associated with more aggressive phenotype and poor prognosis with resistance to certain chemotherapeutic agents.

Trastuzumab administration as an adjuvant and in metastatic HER2 positive breast cancer is associated with both symptomatic and asymptomatic cardiotoxicity. The incidence of trastuzumab-mediated cardiotoxicity were 27% with antracycline combination and 13% when it was administered with paclitaxel .

Pertuzumab, a recombinant humanized monoclonal antibody binding to the HER2 dimerization domain, prevents dimerization of HER2 with other HER receptors (HER3,HER1, and HER4) especially with HER3. Blocking HER2-HER3 dimerization is postulated to be the most clinically relevant action of pertuzumab and this can effectively block her2-mediated cell signaling.

Pertuzumab is indicated in combination with trastuzumab and docetaxel for the treatment of patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease.

Treatment of breast cancer with pertuzumab plus trastuzumab plus docetaxel as first line treatment until disease progression might be complicated by cardiotoxicity in up to 14.5% of the Patients.

Cardinale et al showed that troponin I (TNI) positive identifies trastuzumab-treated patients who are at risk for cardiotoxicity and are unlikely to recover from cardiac dysfunction despite HF therapy.

There is very little data about the reversibility and identification of patients at risk for ca

Detailed Summary:

Breast cancer is the leading cancer in women in Israel with 4000 new cases every year.

Approximately 15-25% of all breast cancers are human epidermal growth factor receptor 2 (HER2) positive and it has been well known that HER2 overexpression is associated with more aggressive phenotype and poor prognosis with resistance to certain chemotherapeutic agents.

Trastuzumab, an anti-HER2 humanized monoclonal antibody, is the standard treatment for both early and metastatic HER2-positive breast cancer. In addition to other chemotherapeutic agents, trastuzumab significantly improves response rate and survival in HER2-positive early and metastatic breast cancer. Although it is well known that trastuzumab therapy is closely associated with both symptomatic and asymptomatic cardiotoxicity.

Addition of trastuzumab to chemotherapy significantly improved response rate, time to disease progression and reduction of death compared to chemotherapy alone in HER2-positive metastatic breast cancer (MBC). Thus, anti-HER2 treatment is a standard therapeutic approach for HER2-positive MBC patients with visceral crisis. Trastuzumab administration as an adjuvant and in metastatic HER2 positive breast cancer is associated with both symptomatic and asymptomatic cardiotoxicity. The incidence of trastuzumab-mediated cardiotoxicity were 27% with antracycline combination and 13% when it was administered with paclitaxel .

Pertuzumab, a recombinant humanized monoclonal antibody binding to the HER2 dimerization domain, prevents dimerization of HER2 with other HER receptors (HER3,HER1, and HER4) especially with HER3. Pertuzumab differs from trastuzumab in the epitope binding regions of the light chain; pertuzumab binds to domain 2 ofHER2 essential for dimeriza
Sponsor: Rambam Health Care Campus

Current Primary Outcome:

• To assesses blood levels of TNI and BNP during the first four cycles Trastuzumab&Pertuzumab and Taxanes treatment [ Time Frame: The patients will be followed until the end of therapy (an expected average of 18 months). ]
  Prior to every treatment cycle, blood samples will be taken for TNI & BNP. Patients with elevated levels will be sent for LEVF evaluation. In cases with LEVF reduction of 15% or more from the baseline or LEVF less than 50% will be sent for Cardiological consult in order to consider ACEI or BB treatment
• To evaluate the correlation between elevated TNI&BNP and decline of LVEF on echocardiography until end of treatment. [ Time Frame: The patients will be followed until the end of therapy (an expected average of 18 months). ]
  Prior to every treatment cycle, blood samples will be taken for TNI & BNP. Patients with elevated levels will be sent for LEVF evaluation. In cases with LEVF reduction of 15% or more from the baseline or LEVF less than 50% will be sent for Cardiological consult in order to consider ACEI or BB treatment

Original Primary Outcome: Same as current

Current Secondary Outcome:

Original Secondary Outcome:

Information By: Rambam Health Care Campus

Dates:
Date Received: March 5, 2014
Date Started: May 2014
Date Completion: August 2016
Last Updated: May 1, 2014
Last Verified: May 2014