Posts Tagged ‘metastatic breast cancer’

New Treatment for Her-2+ Metastatic Breast Cancer Opens at CORT

September 4, 2009

CORT has opened the Wyeth 3144A2 3005 WW Study testing the oral her-2 inhibitor, neratinib, in combination with paclitaxel (Taxol), versus standard therapy with trastuzumab (Herceptin) in combination with paclitaxel, for first-line treatment of her-2+ metastatic breast cancer. 

Neratinib is an oral anti-her-1/her-2 drug with demonstrated efficacy in metastatic her-2 positive breast cancer.  The safety studies have demonstrated acceptable and manageable toxicity of neratinib, including rash and occasional loose stools or diarrhea being most common.  As with other her-2 inhibiting drugs, neratinib may lower the cardiac ejection fraction, so serial monitoring of cardiac function is routine.  The Phase III study will compare the efficacy and tolerability of paclitaxel with either oral neratinib or trastuzumab (a monoclonal antibody against her-2 protein, given IV).

The potential advantages of neratinib include improved convenience (and possibly improved safety).  The drug is given orally.  

For more information about this study, visit our website at www.CORTPA.com, or contact a Research Coordinator at 972-566-5588.  

Patients with her-2+ breast cancer may also be eligible for other studies and treatment at CORT, including non-study therapy.  The principle investigator at CORT is Dr. Barry Mirtsching.  He has personally conducted over 200 trials in cancer therapy over 16 years, many in breast cancer management.  Experience in both trial and non-trial breast cancer management benefits patients by producing better treatment outcomes.  Care at CORT is individual and personal, with adequate time for problem-solving and direct contact with the physician.

STRIDE Breast Cancer Study Testing Stimuvax Cancer Vaccine Open at CORT

September 4, 2009

CORT has opened the STRIDE study for first-line treatment of metastatic, hormone-receptor positive breast cancer.  The study will test standard anti-estrogen therapy in combination with a vaccine placebo, versus standard anti-estrogen therapy with the Stimuvax cancer vaccine.  The press release regarding this study is posted below.

For more information about this study, or to schedule appointments for evaluation and treatment of metastatic breast cancer, visit the CORT website at www.CORTPA.com, or call 972-566-5588 and ask to speak with a Patient Care Coordinator or CORT Research Nurse. 

STRIDE Press Announcement:

24 Jun 2009 – Merck KGaA announced the initiation of its global Phase III clinical study of the therapeutic cancer vaccine Stimuvax® (BLP25 liposome vaccine, L-BLP25) in patients with advanced, inoperable breast cancer. The STRIDEa study will determine if Stimuvax can extend progression-free survival in patients treated with hormonal therapy who have hormone receptor-positive, locally advanced, recurrent or metastatic breast cancer. Overall survival, quality of life, tumor response and safety will also be assessed in this study. The STRIDE study will be supervised by an expert Steering Committee and is sponsored by Merck, which is leading the development of Stimuvax.
STRIDE will enroll more than 900 patients with advanced breast cancer at an estimated 180 sites in over 30 countries – within North America, Europe, Asia and Australia; the Principal Investigator is Dr Lawrence Shulman, Chief Medical Officer and Senior Vice President for Medical Affairs, Dana-Farber Cancer Institute, Boston, USA.
 
Stimuvax is an investigational therapeutic cancer vaccine designed to stimulate the body’s immune system to identify and target cancer cells that express MUC1, an antigen commonly expressed in breast cancer as well as in other common cancer types such as non-small cell lung cancer (NSCLC), multiple myeloma, and colorectal, prostate and ovarian cancers.
 
The Phase III program for Stimuvax was initiated following results from a randomized Phase IIb study of 171 patients with inoperable stage IIIb NSCLC, in which Stimuvax showed a trend towards extending median overall survival from 13.3 months for patients receiving best supportive care (BSC) to 30.6 months for patients receiving Stimuvax plus BSC. Reported side effects included mild-to-moderate flu-like symptoms, gastrointestinal disturbances and mild injection-site reactions. A further long-term safety analysis in 16 patients receiving prolonged treatment with Stimuvax from 2 to 8.2 years showed the most common treatment-related adverse events were injection-site reactions (ISRs) with no evidence of autoimmune reactions. These data also show that the occurrence of ISRs decreased with long-term therapy (>1 year).

First-Line Chemotherapy for Her-2 Negative Metastatic Breast Cancer

January 12, 2009

Paclitaxel (Taxol) chemotherapy in combination with Bevacizumab (Avastin) has become a standard treatment regimen for her-2 negative patients with metastatic breast cancer, based on findings of improved outcomes with the combination in the ECOG 2100 study.  That trial  compared paclitaxel alone to paclitaxel and bevacizumab combination therapy.  For the combination, response rate was improved (30% vs. 14%, p<0.0001) and progression-free survival was improved (11.4 mos. vs. 6.1 mos; HR=0.51, p<0.0001).  Bevacizumab was approved for treatment of metastatic breast cancer based on these results. 

Many patients may not be appropriate for the combination of paclitaxel and bevacizumab therapy.  Patients who have received prior taxane therapy in the adjuvant setting (particularly with a short disease-free interval to the time of metastatic disease) may increased risk for resistance to taxane therapy.  Patients who are diabetic may have exacerbation of diabetes because of corticosteroid premedication required before taxane therapy.  Patients with neuropathy may have worsening of neuropathy with taxane therapy.  

For these patients,  therapy with another chemotherapy agent in combination with bevacizumab may be considered.    However, clinical trial data supporting the combination of other chemotherapy agents with bevacizumab is limited, and insurer coverage may be restrictive.   An example of an alternative regimen would be gemcitabine (Gemzar) and bevacizumab.   No corticosteriod premedications are required for gemcitabine therapy, and there is no risk of neuropathy. 

Other important clinical circumstances may make the use of bevacizumab unattractive, such as severe hypertension, angina or recent ischemic events from coronary or cerebrovascular disease, thrombosis risk, bleeding, or the presence of CNS metastatic disease.  Bevacizumab may cause proteinuria, increased blood pressure, bleeding, thrombosis, infusion reactions, delayed wound healing, or other rare toxicities (bowel perforation). 

For more information about breast cancer therapy and clinical trial information, contact a CORT Research Coordinator at 972-566-5588 (Dallas) or 972-981-4012 (Plano), or visit our website at www.CORTPA.com.

TDM1 (Trastuzumab-DM1) Immunoconjugate Drug Therapy Study Open at CORT

December 10, 2008

A phase III study of Trastuzumab-DM1 for treatment of relapsed her-2 positive metastatic breast cancer is open at CORT. 

Trastuzumab (Herceptin)  is a monoclonal antibody against the her-2 protein, which is overexpressed or amplified in an aggressive subset of breast cancers.  Trastuzumab and chemotherapy combination therapy has substantially improved response, progression-free survival, and overall survival of metastatic her-2 positive breast cancer patients.  Trastuzumab is approved for treatment of metastatic breast cancer.  Trastuzumab may be associated with uncommon infusion reactions and myocardial dysfunction, which may produce clinical congestive heart failure in about 1% of patients, which may be reversible in some cases with discontinuation of therapy.  When her-2 positive metastatic breast cancer progresses on a first-line trastuzumab + chemotherapy regimen, continuing trastuzumab (or another anti-her-2 drug) in the second-line treatment setting (with a different chemotherapy drug) is beneficial with regard to response and stopping disease progression (compared to therapy with chemotherapy alone). 

Lapatinib (Tykerb) is an oral drug that inhibits the intracellular, activating portion of the her-2 molecule.  It has been approved (in combination with capecitabine (Xeloda)) for treatment of metastatic her-2 positive breast cancer that has progressed after trastuzumab-based initial therapy. 

Trastuzumab-DM1 (TDM1) is a drug that combines trastuzumab with a linked chemotherapy agent, maytansine (DM1).   This linkage of an antibody and a drug is termed an immunoconjugate.  The potential advantage of immunoconjugate therapy is that the antibody targets DM1 specifically into tumorous tissue, which may reduce the toxicity of treatment.   In addition, the antibody trastuzumab has it’s own anti-cancer activity.  TDM1 has been tested in open-label phase I and II studies, with mild toxicities and effectiveness, even in heavily pre-treated her-2 positive metastatic breast cancer.  Adverse events that have been noted include elevated liver function tests, fatigue, anemia, and thrombocytopenia. 

The Phase III study at CORT is part of a large multicenter national study.  The study will test the activity of trastuzumab-DM1 versus standard therapy (lapatinib-capecitabine) for second-line therapy of patients with metastatic her-2 positive breast cancer.

For more information about this study, consultation, or referral, contact a CORT Research Coordinator at 972-566-5588, or visit our website at www.CORTPA.com.

Abraxane (nab-paclitaxel) with or without Herceptin in First-Line Treatment of Metastatic Breast Cancer: ION 04-012 Study Results from the ASCO 2008 Annual Meeting

June 12, 2008

The International Oncology Network (ION) Study 04-012 results were presented in a poster presentation at the ASCO 2008 Annual Meeting.  This study was an open label Phase II study of Abraxane (nab-paclitaxel) therapy at 125 mg/M2 weekly for three out of four weeks, cycles every 4 weeks for first-line treatment of patients with metastatic breast cancer.  Patients with her-2 overexpressing or amplified disease also received Herceptin on a standard weekly schedule. 

This is a copy of the poster:

04-012-asco-poster-5-20-08

Abraxane is a protein-bound paclitaxel formulation, which can be given over shorter infusion duration than other taxanes, and it has a low rate of allergy or infusion reactions because it is cremaphor solvent-free.  Abraxane infusions do not require steroid premedication.   In previous studies of Abraxane in metastatic breast cancer, encouraging activity has been noted, even in pre-treated patient groups.  The response rate seen with Abraxane in other studies appears to be comparable or superior to responses seen with other taxane drugs. 

The ION Study enrolled 72 patients.  At the time of the analysis, 47 were evaluable for response.  There were 29 her-2 negative patients and 17 her-2 positive evaluable patients.  One patient had her-2 unknown status.  In the her-2 negative group, there were 9 partial responses (31%) and 18 (62%) patients with stable disease.  In the her-2 positive group, there were 2 complete responses (12%), 9 partial responses (53%), and 5 (29%) patients with stable disease.   Therefore, the overall response rate in her-2 positive patients was 65%.   Overall, for all patients, the response rate was 43%.  Median time to progression was 15.9 months, and median overall survival was 25 months.

Treatment was well tolerated and grade >=3 toxicities were mostly limited to neutropenia and/or fatigue.  Infections were uncommon. 

Dr. Barry Mirtsching of CORT was the Principle Investigator of this study.   Special thanks to Abraxis Oncology, the many ION investigator physicians, study coordinators, and participating patients who helped make this research study possible.  

ION is continuing to study Abraxane therapy in the setting of metastatic breast cancer.  Dr. Mirtsching at CORT is also the Principle Investigator for the study of Abraxane and Sorafenib (Nexavar) for first-line therapy of metastatic breast cancer.  Sorafenib is an oral drug with anti-angiogenic activity.  It is approved for the treatment of metastatic renal (kidney) cancer.  The combination of anti-angiogenic drugs and taxane therapy has shown promise in treatment of metastatic breast cancer.  Bevacizumab (Avastin), a monoclonal antibody with anti-VEGF (vascular endothelial growth factor) activity, and paclitaxel has been shown to improve progression-free survival when compared to paclitaxel alone.  Sorafenib would be a significant advance for breast cancer patients if it proves to be as active as Avastin, because it is oral and has a generally more favorable toxicity profile than Avastin.  Abraxane was chosen in this study for the clinical advantages noted previously.

For more information about the ION 06-025 Study of Abraxane and Sorafenib, please call 972-566-5588 (Dallas), or 972-981-4012 (Plano), or visit the www.CORTPA.com

Ixabepilone (Ixempra) Approved for Metastatic Breast Cancer

October 20, 2007

Ixabepilone (Ixempra) was approved on 10/16/07 for treatment of metastatic breast cancer.  The specific approval is: (1) Ixebepilone in combination with capecitabine (Xeloda) for treatment of metastatic or locally advanced breast cancer patients who have become resistant to anthracycline (such as Adriamycin) and taxane therapy (such as Taxotere or Taxol), or for patients who are resistant to taxane therapy, in whom further anthracycline therapy is contraindicated, and (2) Ixebepilone as monotherapy for treatment of metastatic or locally advanced breast cancer patients whose tumors are resistant to anthracyclines, taxanes, and capecitabine.

CORT was part of the multicenter study that established the efficacy of ixabepilone, and our physicians and nurses are experienced in management of this treatment.  CORT applauds the FDA decision to approve this drug, which should expand the treatment choices for these patients who have limited other treatment options.  For more information about treatment with ixabepilone, contact the CORT office at 972-566-5588 (Dallas), or at 972-981-4012 (Plano).  Information about CORT and the innovative treatments and studies offered can be found at our website: www.CORTPA.com.

nab-Paclitaxel (Abraxane) and sorafenib (Nexavar) for First-Line Treatment of Metastatic Breast Cancer

September 28, 2007

Barry C. Mirtsching, MD at CORT is the lead investigator for the International Oncology Network (ION) trial of Abraxane and sorafenib (Nexavar) for first-line treatment of metastatic breast cancer. Nexavar is an oral drug with anti-angiogenic and anti-proliferative activity in cancer. It is FDA-approved in the treatment of metastatic renal (kidney) cancer. Nexavar has single-agent activity demonstrated in a phase II study in metastatic breast cancer. The combination of anti-angiogenic drugs and chemotherapy has shown promise in breast cancer treatment. The ION phase II study will test the efficacy of the Abraxane and Nexavar combination therapy for first-line treatment of metastatic breast cancer. The risks of treatment include fatigue, rash, allergic reaction, nausea, vomiting, diarrhea, sensory neuropathy, increased blood pressure, slow wound healing, proteinuria, thrombosis, bleeding, and low blood counts.

For more information on these studies, visit www.CORTPA.com, or speak with a Study Coordinator at 972-566-5588.

Denosumab (AMG 162) for Treatment of Breast Cancer with Bone Metastases

September 28, 2007

Receptor activator of NF-B ligand (RANKL) is a key mediator of osteoclast (bone dissolving cells) formation, function, and survival. Denosumab, a fully human monoclonal antibody, binds and inhibits RANKL, thus suppressing excess osteoclastic activity associated with bone metastases. In a phase II Study of denosumab versus standard IV bisphosphonate therapy, denosumab treatment resulted in rapid and sustained suppression of bone turnover and was at least as effective as IV BP at reducing the risk of skeletal related events (fractures, pain), with a safety profile similar to that seen in advanced breast cancer pts receiving cancer treatment. Adverse events (AE) among all pts included nausea, vomiting, asthenia, diarrhea, and bone pain. Osteonecrosis of the jaw (ONJ), a serious but uncommon complication of bisphosphonate therapy, ash not been observed with denosumab. Denosumab does not affect renal function. Bisphosphonate therapy may reduce renal function, so monitoring is required. Patients with renal dysfunction may not be able to receive bisphosphonates, or dose reductions are required.

CORT is conducting a randomized, double-blind study of denosumab versus IV zoledronic acid (Zometa) bisphosphonate therapy for treatment of metastatic breast cancer patients with bone metastases.

For more information on these studies, visit www.CORTPA.com, or speak with a Study Coordinator at 972-566-5588.

E7389 (Eribulin Mesylate) Phase III Study for Refractory Metastatic Breast Cancer

September 28, 2007

E7389 (Eribulin) is a synthetic analog of halichondrin B (HB), which is a natural marine product extracted from marine sponge Halichondria okadai, and had shown in preclinical studies to have highly potent anti-cancer activity in vitro and in vivo. Eribulin has demonstrated activity in refractory breast cancer. Eribulin was evaluated in a single-arm Phase II trial in female patients with refractory breast cancer, ECOG performance status of 0–1, measurable disease, and neuropathy Grade 2. Patients had received a median of 4 prior chemotherapy regimens. The overall response rate was 15%, which is high, considering the population of resistant patients treated. 1/3 of patients did not progress in 6 months. The most common drug related toxicities were neutropenia (low white blood cell count), fever, fatigue, alopecia (hair loss), nausea, and anemia.

CORT is conducting a Phase III study of Eribulin versus the treatment of physician’s choice’ in patients with locally recurrent or metastatic breast cancer. Patients are eligible if they have been previously treated with at least two and a maximum of five prior chemotherapy regimens, Including an anthracycline and a taxane.

For more information on these studies, visit www.CORTPA.com, or speak with a Study Coordinator at 972-566-5588.

Sunitinib (Sutent) in Metastatic Breast Cancer and Triple-Negative (ER-,PR-, and Her-2-negative) Breast Cancer

September 27, 2007

Breast cancers that do not contain growth regulator proteins for estrogen receptor (ER), progesterone receptor (PR), or HER-2 are termed “triple negative” tumors. Triple negative tumors are aggressive. Patients with metastatic triple negative tumors have a poor prognosis when treated with standard therapies.Sutent® (sunitinib) is an oral targeted drug that blocks growth promoting receptors PDGF-R and VEGF-R. It blocks angiogenesis, the process of new blood vessel growth in tumors. Without new blood vessel formation, tumor growth is inhibited.The risks of Sutent are hypertension, abdominal pain, slow wound healing, changes in blood chemistry or blood counts, reduced thyroid function, and bleeding. Rare cases of reduced heart function or brain white matter injury have occurred.

CORT is conducting a study to evaluate the addition of Sutent versus standard chemotherapy in patients with triple negative metastatic breast cancer. Several standard treatments are allowed in this study, and the physician may choose the one felt most appropriate for the individual patient. The study will determine is Sutent has comparable or superior activity to standard treatments in this high risk group of patients.Anti-angiogenic treatment added to standard chemotherapy for metastatic breast cancer has already been shown to increase disease response to treatment and prolong disease control.

CORT is conducting a study of study comparing standard therapy with two drugs, bevacizumab (Avastin) and paclitaxel (Taxol) to the combination of Sutent and Taxol. Avastin is an antibody that blocks angiogenesis, with risks similar to those of Sutent. Avastin requires intravenous administration, and occasional infusion reactions (allergic reactions) do occur. The study will determine is Sutent is comparable or superior to Avastin, when either is combined Taxol with chemotherapy.

For more information about these studies, visit www.CORTPA.com or contact a Research Coordinator at 972-566-5588.