Cleveland Clinic to Study Next Generation Genomic Sequencing
The field of genomics is expanding rapidly – beyond simply identifying genes that predict a patient’s cancer risk. Oncologists are increasingly able to individualize a patient’s cancer treatment after identifying genetic mutations in a tumor – ones that may be absent from all the patient’s other cells.
Cleveland Clinic is at the forefront of this type of personalized medicine through a unique collaboration with Foundation Medicine, a cancer diagnostics company specializing in comprehensive genomic analysis of tumors. For the next year, cancer patients diagnosed with one of 15 specific solid tumors with historically poor prognosis or limited treatment options will have the opportunity to participate in a study where their tissue sample will be sent to Foundation Medicine for targeted genetic sequencing.
The study, led by Davendra Sohal, M.D., MPH of Taussig Cancer Institute, will determine if this type of genomic sequencing is a feasible undertaking for Cleveland Clinic and whether or not it impacts treatment options for patients.
Participating patients’ tissue samples will be analyzed across a panel of more than 230 cancer-related genes to provide information on the tumor’s composition and any specific mutations that could affect treatment. Once the analysis is complete, an independent team of Taussig Cancer Institute oncologists will review the results and recommend a personalized treatment plan which could include chemotherapy, radiation and/or participation in a clinical trial that may benefit the patient.
“Personalized medicine is changing the way we treat cancer,” says Brian J. Bolwell, M.D., FACP, chairman of Cleveland Clinic’s Taussig Cancer Institute. “Knowing the specific genetic composition of a tumor may allow us to create precise, individual treatment plans for patients rather than relying on standard treatments that could be ineffective while increasing healthcare costs.”
Advances in genomics, like this collaboration between Cleveland Clinic and Foundation Medicine, provide an unprecedented opportunity to identify and treat cancer more effectively.
Taussig Cancer Institute Welcomes New Staff
Alok Khorana, MD, has joined Cleveland Clinic Taussig Cancer Institute as the Sondra and Stephen Hardis Chair in Oncology and Director of the Gastrointestinal Malignancies Program. He most recently served as Vice Chief, Division of Hematology/ Oncology, and an associate professor of medicine and oncology at the James P. Wilmot Cancer Center, University of Rochester. His clinical and translational research focuses on predictive factors in gastrointestinal cancers and cancer-associated thrombosis. Dr. Khorana serves on the American Society of Clinical Oncology (ASCO) Clinical Practice Guidelines Panel and the ASCO Scientific Program Committee and on gastrointestinal committees of the Southwest Oncology Group and American College of Surgeons Oncology Group. Currently, he is chair of the International Society on Thrombosis and Haemostasis scientific subcommittee on hemostasis and malignancy. “My goal is to make Cleveland Clinic’s gastrointestinal cancer program as patient-centered as possible,” says Dr. Khorana. “Patient-centeredness not only means that providers are highly accessible, it means that we provide individualized therapy, using the revolution in genomic medicine and tumor mutational analysis to provide each patient with the most effective treatments and access to cutting-edge clinical trials.” Dr. Khorana earned his medical degree from The Maharaja Sayajirao University of Baroda (Gujarat, India). He completed both an internship and a residency in internal medicine at the University at Buffalo. He also completed a fellowship in hematology/oncology at the University of Rochester.
Mitchell R. Smith, MD, PhD, has been named Director of the Lymphoid Malignancy Program at
Cleveland Clinic Taussig Cancer Institute. Dr. Smith joined Cleveland Clinic in 2012, after 19 years as Director of the Lymphoma Program at Fox Chase Cancer Center in Philadelphia. His research has focused on developing targeted approaches to improve therapy of lymphoma and myeloma. The Leukemia and Lymphoma Society honored Dr. Smith with a Lifetime Achievement Award for his work with lymphoma. Dr. Smith is an active member of the American Society of Clinical Oncology, the American Association for Cancer Research, the American Society of Hematology and the Eastern Cooperative Oncology Group. He also has been a member of the National Comprehensive Cancer Network guideline committees for non- Hodgkin’s lymphoma and myeloma. “In addition to maintaining our excellent quality of care and collaborating with researchers to make targeted agents work better, my goal for the Lymphoid Malignancy Program is to enhance our clinical research efforts,” says Dr. Smith. “I plan to increase the range of available clinical trials and the number of our patients enrolling in them. My vision includes having selected trials open in our regional locations, where many patients are initially treated, while having drugs earlier in development available at main campus for patients requiring those options.” Dr. Smith earned his medical degree and a doctorate in experimental pathology at Case Western Reserve University. He completed a fellowship in medical oncology and biomedical research at Memorial Sloan-Kettering Cancer Center.
Krista Dobbie, MD, comes to Cleveland Clinic from Sentara Healthcare of Virginia, where she served as medical director of palliative medicine. She earned her medical degree from The University of Toledo and completed a residency in internal medicine at Eastern Virginia Medical Center.
Holly Dushkin, MD, earned her medical degree from Temple University. She completed a residency in internal medicine at Temple University Hospital and a fellowship in hematology/medical oncology at Fox Chase Cancer Center.
Harold Goforth, MD, earned his medical degree from Wright State University and completed his adult psychiatry residency at Loyola Medical Center. He is board-certified in hospice and palliative medicine by the American Board of Neurology and Psychiatry and certified in pain medicine by the American Board of Pain Medicine. His areas of focus are pain and symptom management among advanced-stage illnesses and palliative medicine systems development.
Betty Hamilton, MD, earned her medical degree from the University of Chicago. She completed a residency in internal medicine at the Hospital of the University of Pennsylvania and a fellowship in hematology/oncology at Cleveland Clinic.
Deepa Jagadeesh, MD, MPH, earned her medical degree from the University of Mysore (India) and her master’s degree in public health from Boston University. She completed a residency in internal medicine and a fellowship in hematology/oncology at the University of Massachusetts Medical School.
Sudipto Mukherjee, MD, PhD, earned his medical degree from Calcutta University, in addition to a master’s degree in public health (epidemiology) and a doctorate in vision science from the University of Alabama at Birmingham. He completed a residency in internal medicine at William Beaumont Hospital (Royal Oak, Mich.) and a fellowship in hematology/ oncology at Cleveland Clinic.
Tobenna Nwizu, MD, earned his medical degree from the University of Ibadan (Nigeria). He completed a residency in internal medicine at John H. Stroger, Jr. Hospital of Cook County in Chicago and a fellowship in hematology/oncology at University of Chicago Hospitals.
Chirag Patel, MD, earned his medical degree from Northeast Ohio Medical University. He completed a residency in physical medicine and rehabilitation at Pitt County Memorial Hospital and a fellowship in hospice and palliative care at The University of Texas MD Anderson Cancer Center.
Nima Sharifi, MD, earned a bachelor’s degree in biology (summa cum laude) from Virginia Polytechnic Institute and State University. He completed an internship and residency at Yale-New Haven Hospital and medical oncology and postdoctoral fellowships at the National Cancer Institute. Dr. Sharifi’s research focuses on uncovering the fundamental mechanisms of advanced prostate cancer to develop better treatments for men with this disease.
Qing Yi, MD, PhD, comes to Cleveland Clinic from the University of Texas (UT) MD Anderson Cancer Center, where he was a professor of medicine in the Department of Lymphoma/Myeloma, Division of Cancer Medicine, and Center for Cancer Immunology Research. Dr. Yi received his MD from Jiangxi Medical College in Nanchang, China, and his PhD in Immunology from Karolinska Institute, Stockholm, Sweden.
Two Paclitaxel Schedules Shown Equivalent When Used As Adjuvant Therapy for Breast Cancer
Two schedules for paclitaxel as adjuvant therapy for breast cancer are equivalent on the endpoint of disease-free survival.
As part of a SWOG-coordinated trial, 3,294 patients with node-positive or high-risk node — negative operable breast cancer were randomized in a 2x2 factorial design to adriamycin/cyclophosphamide six doses every two weeks or adriamycin/ cyclophosphamide weekly for 15 weeks, and paclitaxel every two weeks for six cycles or paclitaxel weekly for 12 weeks. At first interim analysis, the adriamycin/cyclophosphamide randomization was halted for futility. The trial was subsequently reopened at which time all patients received four cycles of adriamycin/cyclophosphamide, and the randomization to paclitaxel every two weeks or paclitaxel weekly continued.
“We were trying to show that weekly paclitaxel was better. We couldn’t show that; these two ways of giving paclitaxel look the same,” says G. Thomas Budd, MD, staff physician, Taussig Cancer Institute. A Cox model adjusting for the adriamycin/cyclophosphamide arms showed a hazard ratio of 1.08 for weekly paclitaxel compared with every two weeks. There was no significant interaction of the two factors. The estimated five-year progression-free survival was 82 percent for weekly paclitaxel and 81 percent for paclitaxel administered every two weeks.
The side effect profiles were different between the two paclitaxel schedules. Skin rash, allergic reaction and musculoskeletal pain occurred more frequently with paclitaxel administered every two weeks. The higher dose of paclitaxel and the use of pegfilgrastim with the every-two-week schedule may have contributed to the excess toxicity observed in this arm, says Dr. Budd.
“The bottom line is that paclitaxel can be given with either one of these schedules, but the toxicity appears to be a bit less with weekly paclitaxel,” he says.
Taussig Cancer Institute Clinical Trials
Disease(s): Leukemia, Acute Myeloid (AML), Myelodysplastic Syndrome (MDS)
A Phase 1 Study of Sequential Idarubicin + Cytarabine, Followed by Lenalidomide, in Patients with Myelodysplastic Syndrome (RAEB-2) or With Previously Untreated Acute Myeloid Leukemia
Objective: To determine the maximum tolerated dose of lenalidomide following cytarabine and idarubicin as induction chemotherapy.
Disease: Myeloproliferative Neoplasms
A Phase 2 Study of LY2784544 in Patients with Myeloproliferative Neoplasms
Objective: The primary objective of the study is to assess the activity of LY2784544 therapy administered once daily, as measured by objective response rate in patients with the myeloproliferative neoplasms: PV, ET, and MF, including those who have demonstrated an intolerance to, failure of primary response to, or have demonstrated disease progression while on ruxolitinib.
A Phase II Randomized Study of Rituximab, Methotrexate, Vincristine & Cytarabine with and without Low-Dose, Whole-Brain Radiotherapy for Primary Central Nervous System Lymphoma
Objective: This study uses a multidrug regimen for an uncommon tumor type and allows patients with lymphoma in any one or more of the following CNS sites: brain, CSF, spinal cord or eyes.
Phase II study of TKI258 (Dovitinib) in patients with recurrent or progressive glioblastoma who have progressed on anti-angiogenic therapy (including anti-VEGF therapy)
Objective: Dovitinib targets both FGF (fibroblast growth factor) and VEGF (vascular endothelial growth factor) in this patient population for whom no active agents exist.
Randomized Phase II Four Arm Study In Patients 60 with Previously Untreated Mantle Cell Lymphoma of Therapy with: Arm A = Rituximab+ Bendamustine Followed by Rituximab Consolidation; Arm B = Rituximab + Bendamustine + Bortezomib Followed by Rituximab Consolidation; Arm C = Rituximab + Bendamustine Followed by Lenalidomide + Rituximab Consolidation; Arm D = Rituximab + Bendamustine + Bortezomib Followed by Lenalidomide + Rituximab Consolidation
Objective: To determine whether the addition of bortezomib (RBV) to an induction regimen of rituximab-bendamustine (RB) improves progression-free survival (PFS) compared with RB alone in patients ≥ 60 years of age with previously untreated mantle cell lymphoma. Also, to determine whether the addition of lenalidomide to a consolidation regimen of rituximab following an induction regimen of RB or RBV improves PFS compared with consolidation rituximab alone in this patient population.
Randomized Phase II study of maintenance pemetrexed vs. observation for patients with malignant pleural mesothelioma without progression after first-line chemotherapy
Objective: To determine if maintenance therapy with pemetrexed improves progression-free survival in patients with malignant pleural mesothelioma who have at least stable disease after completion of first-line therapy with pemetrexed plus cisplatin or carboplatin.
An open-label, randomized, Phase II, parallel, dose-ranging, multicenter study of sotatercept for the treatment of patients with anemia and low- or intermediate-1 risk myelodysplastic syndromes or nonproliferative chronic myelomonocytic leukemia (CMML)
Objective: To determine a safe, tolerable and effective dose of sotatercept that results in the greatest frequency of erythroid hematological improvement (HI-E) in patients with anemia and low- or intermediate-1 risk MDS.
Disease: Multiple Myeloma
A Phase I/II Trial of Very Low to Low Doses of Continuous Azacitidine in Combination with Standard Doses of Lenalidomide and Low-Dose Dexamethasone in Patients with Relapsed or Refractory Multiple Myeloma
Objective: To define the highest-tolerated low dose (HTLD and HTLD CKD for GFR < 60 mL/min and 30-59 mL/min, respectively) and safety of azacitidine given at low but increasing doses up to 50mg/ m^2 twice a week concurrently with GFR-adjusted lenalidomide and low dose dexamethasone in patients with relapsed or refractory multiple myeloma.
Disease: Myeloproliferative Neoplasms
A Phase II Study of LY2784544 in Patients with Myeloproliferative Neoplasms
Objective: To assess the activity of LY2784544 therapy administered once daily, as measured by objective response rate in patients with the myeloproliferative neoplasms PV, ET and MF, including those who have demonstrated an intolerance of, failure of primary response to, or have demonstrated disease progression while on ruxolitinib.
A Phase II Study to Evaluate the Efficacy and Safety of GS-6624 in Adult Subjects with Primary, Post Polycythemia Vera or Post Essential Thrombocythemia Myelofibrosis
Objective: To evaluate the effects of GS-6624 on bone marrow fibrosis alone and in combination with stable doses of ruxolitinib in subjects with PMF and post-PV MF or post-ET MF.
Disease: Prostate Cancer
A Phase 2 Study of Enzalutamide in patients with High-risk Prostate Cancer who have undergone local definitive therapy with Radical Prostatectomy
Objective: The primary objective of the study is to evaluate the clinical efficacy of enzalutamide in patients with high risk prostate cancer with regards to time to disease progression (defined by biochemical recurrence). The study will also be assessing the safety of enzalutamide in patients with high risk prostate cancer, determining the presence of circulating tumor cells in this patient population and hopes to describe the effects of enzalutamide on the number of circulating tumor in patients who have detectable CTCs prior to study entry.
Disease: Prostate Cancer
Objective: The primary objective of the study is to assess treatment related gastrointestinal (GI) and genitourinary (GU) toxicity for patients who undergo SBRT for localized prostate cancer. Our hypothesis is that toxicity will not be excessive (defined as greater than 15% for either GI or GU) compared to the historical standard of fractionated IMRT with image-guidance (which results in 5% grade 3 GU and 5% grade 3 GI toxicity).
Phase II Prospective Trial Correlating Progression-Free Survival with CYP2D6 Activity in Patients with Metastatic Breast Cancer Treated with Single Agent Tamoxifen
Objective: To correlate CYP2D6 score (0 vs. 1+2) and progression-free survival.
An open-label, Phase II trial of orally administered PF-00299804 in adult patients with relapsed/recurrent glioblastoma (GBM)
Objective: This study has treatment arms that allow patients who have or have not received prior bevacizumab.
Disease: Brain, Glioblastoma
A prospective phase II trial of NovoTTF-100A with Bevacizumab (Avastin) in Patients with Recurrent Glioblastoma
Objective: To determine the efficacy of the combination of bevacizumab and NovoTTF-100A in bevacizumab-naive patients with recurrent GBM as measured by 6-month progression-free survival (PFS6)
A Phase II Evaluation of TRC105 in the treatment of recurrent or progressive glioblastoma after prior antiangiogenic therapy (including anti-VEGF therapy)
Objective: Determine median overall survival in patients with recurrent or progressive GBM who have progressed on anti-angiogenic therapy (including anti-VEGF therapy).
Disease: Brain, Glioblastoma
Phase II study of TKI258 (Dovitinib) in patients with recurrent or progressive Glioblastoma who have progressed on anti-angiogenic therapy (including anti-VEGF therapy)
Objective: To determine 6 month progression-free survival (PFS6) in anti-angiogenic therapy (including anti-VEGF therapy or bevacizumab) naive patients with recurrent glioblastoma (GBM) in patients treated with dovitinib and to estimate time to progression in this patient population in patients with recurrent or progressive Glioblastoma who have progressed on anti-angiogenic therapy (including anti-VEGF therapy).
Advances in Cancer Immunotherapy Regional Meeting
October 4, 2013
8 a.m. - 3 p.m.
Intercontinental Hotel and Conference Center at Cleveland Clinic
The Society for Immunotherapy's regional Advances in Immunotherapy program will be held October 4 at the Intercontinental Hotel and Conference Center at Cleveland Clinic. This CME-accredited program, sponsored by Cleveland Clinic Center for Continuing Medical Education in collaboration with the Case Comprehensive Cancer Center, is specifically designed for the entire unit of care involved in treating cancer. Through several lectures by leading cancer immunologists, this program will summarize central themes in research advances and approvals to facilitate understanding of more sophisticated principles of tumor immunology and immunotherapy, and promote appropriate clinical application. Registration deadline is September 25.