Archive for December, 2008

Study Testing Anti-Angiogenic Drug Therapy for Metastatic Renal Cancer

December 25, 2008

CORT has initiated the SWOG S0717 Study for treatment of metastatic renal cancer that has progressed after prior sunitinib (Sutent) or sorafenib (Nexavar) therapy.   These treatments are standard first-line treatments.  After failure of sunitinib or sorafenib, currently, there is no standard therapy for this disease.  The study will evaluate anti-angiogenic drug therapy. 

Bevacizumab (Avastin) is a monoclonal antibody against VEGF (vascular endothelial growth factor).  VEGF is a key protein that stimulates angiogenesis (new blood vessel growth), when binding to endothelial cell VEGF-receptors (VEGF-R).  Inhibition of VEGF by bevacizumab has proven successful in metastatic breast, lung, and colon cancer, settings where bevacizumab has already been FDA-approved for use.   MEDI-522 (Etaracizumab, Abegrin) is a monoclonal antibody against integrin molecules (av,b3).  Intregins are structural signaling molecules that direct cell movement and attachment, and these are required for new blood vessel growth.  Early phase studies have shown that disruption of vascular growth by anti-integrin molecules results in tumor growth arrest. 

In the S0717 study, patients with metastatic renal cancer will receive either bevacizumab in combination with a placeo MEDI-522 (inactive), or bevacizuamb in combination with active MEDI-522.  All patients will receive active bevacizumab.   This study evaluates whether the combination of anti-angiogenic drug therapy is more active than anti-angiogenic therapy with bevacizumab alone.

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

CORT Clinical Trials Brochure: PDF Version

December 20, 2008

CORT offers a broad array of oncology clinical phase II-III studies for solid tumors and lymphomas.  The attached PDF lists our current or pending studies. For more information about our studies, visit the CORT website at www.CORTPA.com, or contact a Reseach Coordinator at 972-566-5588. 

CORT Clinical Trials March 2010

Melanoma Study at CORT Testing Targeted Therapeutic Agents

December 17, 2008

Metastatic melanoma remains one of the most difficult to treat malignancies for oncologists.  This cancer of the pigmented cells in the skin, mucous membranes, or retina may eventually spread to other sites such as lymph nodes, other skin sites, lung, bone, liver, or brain.  The disease is rarely curable at such advanced stage, and treatment with chemotherapy has limited benefits in producing response or remissions.  Radiotherapy and surgery may have a limited role in palliation of patients with limited metastatic disease.  The most commonly employed chemotherapy agent is dacarbazine (DTIC), which may produce response in up to 20% of patients, with responses lasting between 3 and 6 months.  Addition of other chemotherapy drugs to DTIC have not significant improved survival outcomes.  While immunotherapy with interferon-alpha (IFN) or interleukin-2 (IL-2) may rarely produce a longer lasting remission, the general response rate is not greater than 10-15%, and toxicities are substantial. 

Important advances in the understanding of melanoma cell biology have been made.  Certain genetic alterations within melanoma cells may trigger or sustain the growth of the cells.  The intracellular signaling proteins b-raf and N-ras are activated in about 60% of melanomas, which promotes cell growth.  Tumors with these mutations (compared to those without) have a shortened clinical course (worsened prognosis).  Research has shown that mutation of either b-raf or N-ras appears to be mutually exclusive in an individual melanoma.   Ras protein localizes to the cell membrane by farnesylation of the protein by the enzyme farnesyl transferase.  This is an important step in the activation sequence of ras protein. 

Loss of function of PTEN (phosphatase and tensin homologue on chromosome 10) is also seen in melanoma.   This leads to activation of the Akt and mTor.  This alteration may be present in 30-60% of melanoma. 

New drugs have been developed that inhibit these intracellular signaling proteins.  Sorafenib (Nexavar), an oral agent already approved for treatment of renal cancer, inhibits b-raf.  CCI-779 (temsirolimus, Torisel), is an IV agent that has already gained approval for treatment of renal cancer.  It inhibits mTor.  R115777 (tipifarnib) is an oral agent that blocks farnesyl transferase. 

The SWOG S0438 Study open at CORT tests two combinations of these drugs in patients with metastatic melanoma that has not been previously treated.  The first combination will be sorafenib and temsirolimus.  The second combination tests sorafenib and tipifarnib.  Patients will be randomly assigned between the two therapies.  Patients must have measurable disease, no brain metastases, and a history of mucosal or cutaneous primary melanoma.  Occular melanoma is not eligible for this study.  

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

Bendamustine (Treanda) Approved for Treatment of Lymphoma

December 10, 2008

Low-grade follicular B-cell lymphoma is diagnosed in 30,000 US patients each year.  The disease is most often diagnosed at an advanced stage, and there is no know curative treatment in such patients.  Older therapy, which included alkylators such as cyclophosphamide, produces response and remissions.  Cyclophosphamide is often given in combination with other drugs such as vincristine (Oncovin) and prednisone, known as the CVP regimen.   Rituximab (Rituxan), is a monoclonal anti-CD20 antibody. CD20 is present on mature B-cells, including low-grade lymphoma.  Rituximab therapy is now extensive used alone or in combination with chemotherapy for treatment of low-grade B-cell lymphoma.  It is FDA-approved in combination with CVP (R-CVP), following CVP as monotherapy “maintanance”, or at relapse.  The use of first-line Rituximab-chemotherapy combinations such was R-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) has been reported to produce response in 97%, with prolonged remission (median progression-free survival=50 months) (Hiddeman, Blood, 2003).  

Relapsed patients have somewhat less responsive disease, and remissions are not expected to be as durable.  

Bendamustine (Treanda) received FDA-approval for treatment of relapsed B-cell follicular low-grade non-Hodgkin’s lymphoma on 11/3/08.  The approval was based on studies demonstrating a high response rate (74%) and long progression-free duration (median 9.3 months) in patient who received bendamustine therapy for relapse of their disease during or within 6 months of a prior rituximab (Rituxan)-containing treatment regimen.   This approval comes within one year of the drug’s initial approval for treatment of chronic lymphocytic leukemia (CLL), another indolent B-cell neoplasm. 

The addition of rituximab to bendamustine therapy (R-Treanda) has been studied in a phase II study, producing response in 92% of patients (41% complete responses), with median progression-free survival of 23 months.  (Robinson, Journal of Clinical Oncology, 2008).  

In addition to offering our patients bendamustine therapy as an option for management, CORT is conducting a trial of rituximab +/- galiximab (anti-CD80 monoclonal antibody).  This study will test whether dual antibody therapy improves outcome compared to rituximab alone, for relapsed, but rituximab-sensitive disease. 

For more information about bendamustine (Treanda) therapy or lymphoma therapy options at CORT, contact a Clinical Care Coordinator at 972-566-5588, or visit our website at www.CORTPA.com.

C90202 Study: Reducing of Skeletal Morbidity in Metastatic Prostate Cancer

December 10, 2008

Prostate cancer most commonly spreads to bone, primarily in the spine and pelvis.  Patients most often present with a rising PSA (prostate specific antigen) serum level, bone discomfort, weight loss, fatigue, or anemia, depending on the extent of disease.  Some patients may even be asymptomatic at the time that metastatic disease is first determined, for example after a rising PSA is noted and a bone scan is obtained.  Most patients have not had therapy other than local treatment (surgery or RT), although some have had hormonal therapy along with their initial local therapy.  When metastatic prostate cancer is diagnosed, first-line treatment should consist of hormone suppression with LHRH therapy (or orchiectomy, not commonly employed now) to lower the testosterone level.  The addition of anti-androgen drug therapy (e.g., flutamide, biclutamide, or nilandron) to LHRH therapy may also be considered.  Such therapy often will cause disease regression in such “hormone sensitive” or “androgen dependent” metastatic prostate cancer, wtih control of the disease and reduction of the PSA.  Chemotherapy is not considered part of  standard managment during the hormone sensitive phase of metastatic disease, except as part of a research study,  such as the E3805 Study (open at CORT), which tests hormonal therapy with or without doctaxel (Taxotere) chemotherapy in patients with extensive, newly diagnosed metastatic hormone sensitive disease.  Doectaxel is a standard, FDA-approved therapy for treatment of prostate cancer that has become resistant to hormonal therapy.  The E3805 study will determine if the early use of chemotherapy will improve the outcome in patients with metastatic prostate cancer. 

The CALGB Study C90202 for newly diagnosed metastatic hormone-sensitive prostate cancer patients is now open at CORT. This study tests a potent bisphosphonate drug, zoledronic acid (Zometa), compared to placebo therapy, in combination with standard hormonal therapy for patients with metastatic disease, as defined by having at least one bone metastasis on standard imaging.   These patients may have hormone sensitive disease that is less extensive than that which is required in the E3805 study.  

Zoledronic acid is an FDA-approved treatment for patients with bone metastases.  It is most commonly employed in patients with multiple boney lesions who have symptoms.  It is known to reduce bone fractures and pain, events which result in significant morbidity (or mortality) for patients.   Freequently, the use of zoledronic acid is delayed until widespread disease is present,  such as when the disease is becoming resistant to hormonal therapy.  Whether or not the early application of zoledronic acid therapy helps to slow the progression of disease is not known.  The aim of the C90202 study is to de3termine if zoledronic acid reduces bone-related fracture or events in patients with minimal volume of metastatic prostate cancer that is still hormone sensitive. 

Excitement about the use of bisphosphonate drug therapy in cancer treatmetn has excalated, given the provacative findings of the ABCSG Trial 12 study in early breast cancer, which showed that the recurrence rate in these women was reduced by 35%, when zoledronic acid was added to hormonal therapy.  This study found that zoledronic acid (compared to placebo therapy) reduced recurrence of breast cancer not only in bone, but at other sites.  The findings suggest that zoledronic acid has anti-tumor properties that are independent of its effects in bone.  Such a finding may not be limited to patients with breast cancer.  Therefore, a secondary aim of the C90202 study is to determine the overall and progression-free survival impact of zoledronic acid therapy. 

For more information about these studies in hormone sensitive metastatic prostate cancer, contact a CORT Research Coordinator at 972-566-5588, 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.