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Clinical Research Programs

Review clinical research programs by faculty:

Dennis Hallahan, M.D.

Neurobiology and Signal Transduction

The Hallahan laboratory studies the mechanisms of cell death in normal tissues during cancer therapy. In particular, we have found that a signal transduction pathway required for radiation induced apoptosis in normal tissues involves glycogen synthase kinase 3beta. GSK-3beta regulates the apoptosis machinery within normal tissues. Cancer cells do not require GSK-3beta or apoptotic machinery to respond to cancer therapy. In contrast, injuries in normal tissues such as the brain and intestine require GSK-3 signaling. We have found that inhibitors of GSK-3beta prevent injury in normal tissues. These inhibitors prevent injury to the brain and improve neurocognitive function and reduce injury in the intestine of animal models. Presently, we are studying the mechanisms by which GSK-3 inhibition prevents program cell death in normal tissues. Studies involve the epigenetic response to GSK-3 inhibitors. We identify transcription factors and apoptotic machinery that are activated during cancer therapy but inhibited during GSK-3 blockade.

Developmental Therapeutics in Cancer

The Hallahan laboratory has identified several peptides and over a dozen monoclonal antibodies that bind to cancer following treatment with ionizing radiation. Using this strategy, drug delivery can be targeted specifically to cancer and guided by use of a beam of radiation therapy. These targeting ligands have been conjugated to the drug delivery systems, including liposomes and nanoparticles to improve he specificity of drug delivery of cancer. The Hallahan laboratory collaborates extensively with pharmaceutical companies to identify radiation sensitizing and radiation protecting drugs. Pre-clinical efficacy studies were conducted in mouse models of human cancer.

Immunotherapy

The Hallahan laboratory also characterizes the immunological response of antibodies targeted by radiation. These monoclonal antibodies bind to radiation inducible neo-antigens. These antibodies can activate immune response. In addition, therapeutic agents are conjugated to the antibodies to provide cancer specific drug delivery. Identification of radiation inducible neo-antigens involves the co-precipitation of antigens from cancer by use of monoclonal antibodies. Antigens are then identified by use of proteomic technology. Humanization of these mouse monoclonal antibodies will be performed with the goal of bringing antibodies into clinical trials. Optimization and humanization strategies for antibodies is a primary goal of the laboratory.

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Jeffrey Bradley, M.D.

Protocol Title PI Name Protocol Number
IMRT Tomotherapy for Esophagus Cancer: A Phase I Feasibility Study in Non-Operative Patients Bradley, Jeffrey D 06-1070
A Phase I/II Trial of Stereotactic Body Radiation therapy (SBRT) Dose Escalation in the Treatment of Patients with Inoperable Stage I/II Non-Small Cell Lung Cancer Arising within the Zone of the Proximal Bronchial Tree Bradley, Jeffrey D 06-0691
Retrospective Review of Stereotactic Body Radiation Therapy (SBRT) for Cancerous Lesions in the Lung Bradley, Jeffrey D 07-0315
Stereotactic Radiosurgery (SRS) for One or Two Localized Spine Metastases Bradley, Jeffrey D 07-0658
CIRB RTOG 0617 - A Randomized Phase III Comparison of Standard-Dose (60 Gy) Versus High-Dose (74 Gy) Conformal Radiotherapy with Concurrent and Consolidation Carboplatin/Paclitaxel in Patient with Stage IIIA/IIIB Non-Small Cell Lung Cancer Bradley, Jeffrey D RTOG 0617
A Phase II Trial of Stereotactic Body Radiation Therapy (SBRT) in the Treatment of Patients with Operable Stage I/II Non-Small Cell Lung Cancer Bradley, Jeffrey D RTOG 0618

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Perry Grigsby, M.D.

Protocol Title PI Name Protocol Number
Molecular Markers Associated with Poor Prognosis in Cervical Cancer Grigsby, Perry W 05-0294
Treatment Outcomes after Eye Plaque Brachytherapy for Patients with Uveal Melanoma Grigsby, Perry W 05-1070
Differential Gene Expression Profiles in Cervical Cancer Grigsby, Perry W 07-0958
Prospective Data Collection Study of Dosimetry Information for Patients Being Treated with Standard Vaginal Brachytherapy for Gynecologic Cancer Grigsby, Perry W 08-0935
Dosimetry and Toxicity of IMRT Radiation for Gynecologic Cancer Grigsby, Perry W 06-0840
Microarray and Molecular Marker Analysis in Cervical Cancer Grigsby, Perry W 06-1108
Pelvic IMRT with Tomotherapy: A Phase I Feasibility Study in Post-Hysterectomy Endometrial Cancer Patients Grigsby, Perry W 06-0297
Familial Well-Differentiated Thyroid Cancer Grigsby, Perry W 06-0158
Molecular Markers Associated with Poor Prognosis in Hypoxic Colo-Rectal Cancers Grigsby, Perry W 05-0271
FDG-PET in Anal Cancer Grigsby, Perry W 05-0709
Pelvic IMRT with Tomotherapy: A Phase I Feasibility Study in Post-Hysterectomy Cervical Cancer Patients Grigsby, Perry W 05-0977
Functionality of DNA Repair Pathways in Tumor Tissue Correlated with Clinical Outcomes Grigsby, Perry W 07-0178
Roche Elecsys® Thyroglobulin Grigsby, Perry W 07-0572
A Phase II Trial of Samarium 153 Followed by Salvage Prostatic Fossa 3D-CRT or IMRT Irradiation in High Risk, clinically Non-Metastatic Prostate Cancer After Radical Prostatectomy Grigsby, Perry W RTOG 0622
Randomized Phase II Study of Zoledronic Acid vs Observation on Bone Mineral Density and Incidence of Micrometastasis in Women Undergoing Pelvic Radiation for Cervical Cancer Grigsby, Perry W 09-0811

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Jeff Michalski, M.D.

Protocol Title PI Name Protocol Number
Quality Research in Radiation Oncology 2007 Process Survey Michalski, Jeff M 08-0923
Advanced Technology QA Center Michalski, Jeff M 99-0378
A Phase III Randomized Study of High Dose 3D-CRT versus Standard Dose 3D-CRT in Patients Treated for Localized Prostate Cancer (8/21/2008 - ENROLLING ONLY EXISTING PATIENTS INTO THE SUBSTUDY) Michalski, Jeff M RTOG P-0126
A Phase III Study Comparing Combined External Beam Radiation and Transperineal Interstitial Permanent Brachytherapy with Brachytherapy Alone for Selected Patients with Intermediate Risk Prostatic Carcinoma Michalski, Jeff M RTOG 0232
CA - 104342 Dose Volume Analyses of Late Rectal and Bladder Cancer Toxicity Michalski, Jeff M 05-1018
A Phase III Randomized Study of Hypofractionated 3D-CRT/IMRT Versus Conventionally Fractionated 3D-CRT/IMRT in Patients with Favorable-Risk Prostate Cancer CIRB Michalski, Jeff M RTOG 0415
Investigating Markers of Radiation Outcome in Patients with Intermediate-Risk Prostate Cancer Using DNA Microarray Analysis: An RTOG Pilot Study Michalski, Jeff M RTOG 0612
A Phase III Trial of Short Term Androgen Deprivation with Pelvic Lymph Node or Prostate Bed Only Radiotherapy (SPPORT) in Prostate Cancer Patients with a Rising PSA After Radical Prostatectomy Michalski, Jeff M RTOG 0534
Pilot To Reduce Missing RTOG Quality Of Life Data Via Electronic Web-Based Form Collection: A Companion Study For RTOG 0415 (A Phase III Randomized Study of Hypofractionated 3D-CRT/IMRT Versus Conventionally Fractionated 3D-CRT/IMRT In Patients With Favorable-Risk Prostate Cancer) Michalski, Jeff M RTOG 0828
Sub-Study: 3D/OG 9406: A Phase I/II Dose Escalation Study Using Three Dimensional Conformal Radiation Therapy for Adenocarcinoma for the Prostate (existing patients only) Michalski, Jeff M RTOG 94-06
RTOG 0621 Adjuvant 3DCRT/IMRT in Cominbation with Androgen Suppression and Docetaxel for High Risk Porstate Cancer Patients Post-Prostatectomy: a Phase II Trial Michalski, Jeff M RTOG 0621

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Wade Thorstad, M.D.

Protocol Title PI Name Protocol Number
Functional and Quality of Life Assessment in Head and Neck Cancer Patients Status Post Radiation Therapy Thorstad, Wade L 07-0270
Phase II Trial Evaluating Elimination of Radiation Therapy to Pathological N0 Neck(s) with Intensity Modulated Postoperative Radiation Therapy Thorstad, Wade L 07-0142
IMRT Treatment Outcome/Pattern of Failure Analysis Thorstad, Wade L 04-0454
Retrospective FDG-PET/CT for Radiotherapy Treatment Planning Head and Neck Cancer Thorstad, Wade L 05-0745
Retrospective Review of Outcome in Cervical Metastases from Unknown Primaries Thorstad, Wade L 08-0944
Image Bank Protocol for Patients with Head and Neck Cancer Thorstad, Wade L 08-0724
Investigating Predictive Models for Determining Head and Neck Cancer Response to Radiotherapy: An Image Bank Protocol Ancillary Study Thorstad, Wade L 08-1322
A Randomized Phase II Trial of Chemoradiotherapy versus Chemoradiotherapy and Vandetanib for High-Risk Postoperative Advanced Squamous Cell Carcinoma of the Head and Neck Thorstad, Wade L RTOG 0619

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Xiaowei Wang Ph.D.

Protocol Title PI Name Protocol Number
Meta Analysis of High-Throughput Data from Public Databases for Human Cancer Studies Wang, Xiaowei 08-1102

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Imran Zoberi, M.D.

Protocol Title PI Name Protocol Number
Retrospective Review of Factors Affecting the Quality of Breast Brachytherapy Zoberi, Imran 08-0389
Stereotactic Radiosurgery in Patients with Brain Metastasis from Breast Cancer Zoberi, Imran 04-0380
Partial Breast Irradiation (PBI) for Selected Patients with Early Breast Cancer: A Phase I Feasibility Study Zoberi, Imran 05-1053
Intensity Modulated Radiation Therapy for Breast Cancer: A Phase I Feasibility Study Zoberi, Imran 07-1077