Alternative Drug Names:
Nab-Paclitaxel (Abraxane brand in the US), Trastuzumab (Herceptin is the brand in the US and abroad), Pertuzumab (Perjeta brand in the US and abroad)
Purpose of Trial:
The purpose of this phase 2 study is to evaluate the effectiveness of the 3 drug combination (Trastuzumab and Pertuzumab and Abraxane) in HER2+ breast cancers. There are 2 patient populations for this trial – one is newly diagnosed locally advanced breast cancers (including IBC) that overexpress HER2, and have not received any treatment to date for this breast cancer. This group of patients will receive this regimen prior to surgery and pathological complete response rate will be the endpoint. The second group of patients are metastatic breast cancer patients (including IBC), and in this subset of patients, progression-free survival is the endpoint.
Why this study is relevant for IBC patients:
IBC patients currently receive chemotherapy and HER2 targeted therapy (if relevant) prior to surgery to decrease the volume of cancer in the breast and hopefully eradicate any circulating tumor cells. For the 40% of IBC patients who have tumors that overexpress HER2, we know that targeting HER2 in combination with chemotherapy results in synergistic tumor cell kill. Recently we have learned from early breast cancer studies that dual HER2 inhibition results in higher pathological complete response rates than Herceptin alone and we have reason to believe this is true in IBC as well. For this reason in the US, dual HER2 inhibition (using Herceptin and Pertuzumab) has become the standard of care for neoadjuvant chemotherapy that is used in locally advanced and inflammatory breast cancers. For HER2+ recurrences in patients who have not previously received Pertuzumab, the current FDA-approved first-line chemotherapy cocktail often recommended is Herceptin, Pertuzumab and docetaxel. This specific trial opened prior to the FDA approval of Pertuzumab in the neoadjuvant setting, and shortly after the metastatic approval, so the design is similar to today’s standard of care, with the only difference being Abraxane instead of another taxane.
Scientific Details:
Abraxane is a protein-covered version of the chemotherapy drug Paclitaxel. It was developed to avoid the toxicities caused by the harsh chemical solvent needed to dissolve regular Paclitaxel. The active drug in Abraxane (Paclitaxel) acts as an anti-mitotic chemotherapy, and has been approved for breast cancer treatment for many years. There is a known survival benefit to the addition of a taxane such as paclitaxel to anthracycline-containing chemotherapy. Trastuzumab is an antibody that targets HER2, both inhibiting HER2 signaling as well as inducing an immune response to HER2 positive tumor cells. Pertuzumab is another HER2 antibody, but it targets a different site on the HER2 protein than Trastuzumab. It was developed as a dimerization inhibitor, since HER2 must partner with other HER-family proteins (EGFR, HER3 or HER4) to actively signal to downstream growth/survival pathways. The question being asked in this particular study is whether Abraxane can be substituted for docetaxel, which is the FDA-approved taxane partner for Pertuzumab and Herceptin. In clinical practice today, both taxanes are used frequently. Abraxane has superior activity to docetaxel in the metastatic setting, and it offers several additional benefits including the lack of need for steroid premedication, and fewer side effects due to not being dissolved in cremophor.
Trial Information:
This trial is for HER2+ breast cancer patients including IBC patients. Hormone receptor status does not matter. Normal organ function, blood cell composition and heart function is expected. For newly diagnosed IBC patients, no prior treatment is allowed – this trial replaces the standard neoadjuvant chemotherapy phase. For metastatic patients, no prior Herceptin or chemotherapy given in the metastatic setting is allowed, but endocrine therapy is allowed. Also if you have recurred within 12 months of Herceptin, you are not eligible for this trial (usually in this situation, second line therapy for metastatic disease is recommended – for example Kadcyla).
Logistics:
All 3 drugs are given by infusion intravenously (IV). On day 1 of the cycle you will receive all 3 drugs. Pertuzumab is given as an IV infusion in 30-60 minutes, followed by Herceptin also by IV in 30-60 minutes. Abraxane is given over 30 minutes. On day 8 and 15, you will receive Herceptin and Abraxane in a similar timeline. The cycle lasts 21 days – so cycle 2 day 1 begins on day 22 when you will receive all 3 drugs again. If surgery is planned, the planned treatment course is 6 cycles, unless you experience unacceptable toxicity or experience disease progression. For metastatic patients, treatment will continue for as many cycles as tolerable or until disease progression. Follow up visits will be every 3 months for 4 years and then every 6 months for 1 year.
Location of Trial:
Open at 3 City of Hope Campuses in California (Duarte, Lancaster and South Pasadena).
For more information:
Contact the principal investigator for the site nearest you (see below).
For the Duarte site (City of Hope Medical Center), the principal investigator is George Somlo. His email address is gs****@co*.org, and the telephone number is 800-826-4673.
For the Lancaster site (City of Hope Antelope Valley) the principal investigator is Nimit Sudan. His email is ns****@co*.org and the telephone number is 877-828-3627.
For the South Pasadena site (City of Hope-South Pasadena Cancer Center) the principal investigator is Stephen C. Koehler. His email is sk******@co*.org and the telephone number is 800-826-4673.
Is this study NCI Compliant?:
Yes
NCT trial number & link:
NCT# 01730833 – click for more info
Poster from scientific meeting:
Not available
