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

NCT02101879 | Unknown

• 1 other identifier: Cardiotoxicity
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

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 cardiotoxicity of the pertuzumab plus trastuzumab plus docetaxel regimen and of those who will not recover from cardiac dysfunction,this information is crucial. The usefulness of troponin I (TNI) and Brain natriuretic peptide (BNP) in the identification of patients at risk for PT cardiotoxicity and in the prediction of LVEF recovery has never been investigated. based on this background , this study aim is to evaluate the cardiotoxicity of pertuzumab plus trastuzumab plus docetaxel regimen and the application of troponin I (TNI) and Brain natriuretic peptide (BNP) in this setting.

Conditions

Cardiotoxicity.; Anti Her2 Therapy.; Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (2)

• To assesses blood levels of TNI and BNP during the first four cycles Trastuzumab&Pertuzumab and Taxanes treatment

  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

  The patients will be followed until the end of therapy (an expected average of 18 months).

• To evaluate the correlation between elevated TNI&BNP and decline of LVEF on echocardiography until end of treatment.

  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

  The patients will be followed until the end of therapy (an expected average of 18 months).

Study Arms (1)

Breast cancer Her2 positive

Trastuzumab \& Pertuzumab \& Taxanes

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients with Metastatic Breast Cancer Her2 Positive

You may qualify if:

• Metastatic Breast Cancer patients with Her2 Positive Disease.
• No prior treatment

You may not qualify if:

• LEVF less than 50%

Sponsors & Collaborators

• Rambam Health Care Campus: lead

Study Sites (1)

Rambam MC

Haifa, Israel

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples for TNI \& BNP will be sent before every cycle for the first 5 cycles of treatment

MeSH Terms

Conditions

Cardiotoxicity; Breast Neoplasms

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Radiation Injuries; Wounds and Injuries; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

Georgeta Fried, MD

CONTACT

+972-4-854-3018; g_fried@rambam.health.gov.il

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 12 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2014
• First Posted: April 2, 2014
• Study Start: May 1, 2014
• Primary Completion: March 1, 2016
• Study Completion: August 1, 2016
• Last Updated: May 2, 2014

Record last verified: 2014-05

Locations

IL (1)