John R. Floyd II, M.D.

Department: Neurosurgery
Position: Interim Chair, Associate Professor

Personal Statement:

Dr. Floyd obtained an expertise in the surgical management of complex cases including skull base tumors such as clival chordomas, chondrosarcomas, osteosarcomas, meningiomas, schwannomas , pituitary tumors, orbital tumors, sinonasal carcinomas as well as intrinsic brain tumors such as insular gliomas. Dr. Floyd’s surgical experience includes complex spine and peripheral nerve tumors. His training includes a multi-disciplinary approach using micro-neurosurgical techniques, neuroendoscopy and minimally invasive techniques.

Dr. Floyd’s research interests began when he was awarded the NIH Ruth L. Kirschstein National Research Service Award for studying protein expression in intrinsic brain tumors. This research has led to the discovery of possible new biomarkers for diagnosis and treatment, and has been presented at a number of national and international meetings.

 

Dr. Floyd is an active member of the American Association of Neurological Surgeons (AANS), Congress of Neurological Surgeons (CNS), AANS/CNS Section on Tumors, and the North American Skull Base Society.

 

Dr. Floyd is The Carl Raba Family Chair Neuro-Oncology; Program Director


Education:

University of Alabama School of Medicine
University of Adelaide, Adelaide
University of Alabama at Birmingham


Research:

EXPERTISE:
Neuro-Oncology – Translational research for malignant brain tumors

Neurosurgical Oncology – Interest include the surgical treamtent of benign and malignant tumors affecting the brain, spine and peripheral nerves.

Skull Base Surgery – Interests in the surgical management of complex skull base tumors.

PROJECTS:

Clinical Research

06/2015-07/2016 Outcomes in Octagnearians undergoing Craniotomy for Acute SDH, This study involved retrospective examination of survival and predictors of survival for patients age 80 and over, who undergo craniotomy for SDH. Results indicated that initial and first post surgical GCS score are the most powerful predictors of outcome regardless of use of anticoagulant therapy or anti-platelet therapy.

12/2013-04/2014 Clinical outcomes of patients with colorectal carcinoma brain metastasis, This project characterized and described survival for patients with brain metastasis with colon cancer. In this study, patients who received combined modality therapy, surgical excision plus local radiotherapy, in addition to biologics, had significantly improved survival. These results were subsequently published.

01/2013-Present rospective Review of Use of Antiepileptic prophylaxis in Brain Tumors, IRB 20140307HW: This research is on regards to use or nonuse of prophylactic anti epileptics in tumor patients. This has been an ongoing research study, prospective in nature since 2013. The purpose of the study is to collect data regarding use or nonuse of prophylactic anti-epileptic medications in tumor patients, to follow outcomes, and describe the pattern of seizures in tumor patients. this is an ongoing study.

09/2009-Present Tumor Banking and Patient Derived Cell Lines, This is a prospective tumor bank; tissue specimens are collected at the time of surgery, and banked for future research. Additionally, a bank of patient derive cell lines have been developed for future research.

Clinical Trials

08/2012-12/2016 Phase III Clinical Trial for Glioblastoma: IRB HSC20120273H, A Phase III Clinical Trial Evaluating DCVax®-L, Autologous Dendritic Cells Pulsed with Tumor Lysate Antigen for the Treatment of Glioblastoma Multiforme (CTRC# 12-20):

My role was a site Co-PI for this study. This multi-center study involved upfront immunotherapy for newly diagnosed glioblastoma. We were participating site for multi-center Phase III trial. I identified patients prior to surgery who had high probability of glioblastoma (GB). Once consent obtained , specimens were removed at surgery , and prepared for tumor lysate. Later, leukophoresis was preformed to obtain patient specific dendritic cells, which were used to prepare patient specific therapy. This trial is now closed.

Co-Investigator

04/2017-Present Multi Center Trial, convection therapy for glioblastoma, MDNA55, Open Label, Non Randomized , Multi Center Phase 2 Study of Convection Enhanced Delivery (CED) of MDNA55 in Adults with Glioblastoma at First Recurrence or Progression .

MDNA55 is a fusion toxin comprising a genetically engineered circularly permuted interleukin-4 (cpIL-4) fused to a modified version of the Pseudomonas aeruginosa exotoxin A (PE). MDNA55 binds to the IL-4 receptor (IL4R), over-expressed by cancer cells and non-malignant immunosuppressive cells of the tumor microenvironment (TME), and delivers a potent cell-killing agent, PE. A large percentage of glioblastomas (GBs) and their TMEs express IL4R in relatively high amounts, making it a relevant target for MDNA55. Intra- and peritumoral infusion minimizes systemic exposure to the fusion toxin, while the image-guided CED technique enhances exposure of active drug throughout the target region

This is a new clinical trial for which I am Co PI and surgeon. First patient enrolled in 04/17.

03/2015-Present A Dual Phase 1/2, Investigator Initiated Study Rhenium Nanoparticles, A Dual Phase 1/2, Investigator Initiated Study to Determine the Maximum Tolerated Dose, Safety, and Efficacy of Rhenium Nanoliposomes in Recurrent Glioblastoma

This is first in human trial for treatment of recurrent glioblastoma for which I am co-PI. This trial is FDA trial , funded via CTRC Foundation grant to matched funds from CPRIt Grant.

This trial involved unique treatment via convection ( catheter) based therapy with direct instillation of radioactive nanoparticles directly into the recurrent glioblastoma.

Ongoing trial.

06/2013-12/2013 FDA Toxicology Study of Rhenium Nanoparticle in Canines, 186Rhenium Nanoliposomes: A One and 14 Day single Dose Intracranial Injection Toxicology Study in Canines:

This is a FDA toxicity study performed in a GLP lab at MPI Research in Mattawan, MI. This study was supported by CTRC Foundation Grant. I was the Co – PI during this study.

This study involved utilizing rhenium 186 nanoparticles ( RNL 186) convection based therapy.

The primary objective of this study is to assess overall toxicity (both local brain and distant organ) of a single dose administration by the intracranial route of 186Rhenium Nanoliposomes (186RNL). The secondary objective is to evaluate dosimetry following a
single dose administration 186Rhenium Nanoliposomes.

Results in brief demonstrated no local or systemic toxicity secondary to the novel agent. Also, there was excellent regional retention of the RNL186, with no appreciable radiation exposure to other organs including bone marrow.

This study was completed, and enabled FDA approval for first in human phase I trial.

08/2011-Present A Phase 2, Investigator Initiated Study to Determine the Safety, Efficacy a, IRB HSC 20110360H:TH-302 is a nitroimidazole prodrug of the cytotoxin, bromo-isophosphoramide mustard (Br-IPM). When exposed to hypoxic conditions, TH-302 is reduced at the nitroimadazole site of the prodrug by intracellular reductases leading to the release of the alkylating agent Br-IPM. Br-IPM can then act as a DNA crosslinking agent. This drug was utilized in recurrent glioblastoma.

The surgical subsidy involved administering the drug prior to surgery , as well as hypoxyprobe to evaluate tissue hypoxia. The removed specimens were then analyzed for presence of tissue hypoxia, as well as for cross linked DNA.

Goals of study:
• To determine the extent by which TH-302 is able to penetrate the blood brain barrier and affect tumor tissue
• To assess the safety of single dose TH-302 in patients with high grade glioma undergoing surgery
• To assess the safety of TH-302 in combination with bevacizumab for patients with high grade glioma
• To determine the MTD and DLT(s) of TH-302 in combination with bevacizumab

The study is now closed, and manuscript in process.

08/2009-01/2011 A Phase I Study of ANG1005 in Patients with Malignant Glioma, ANG1005 is a conjugate consisting of paclitaxel and Angiopep2. Angioprep2 is a 19 amino acid peptide designed to target the low-density receptor-related protein (LRP). This facilitates transcytosis of drugs across the blood brain barrier (BBB).Once the ANG1005 conjugate reaches the caner cells, it is internalized with subsequent esterase cleavage to release paclitaxel from Angiopep2. In vitro ANG!005 has demonstrated numerous mechanisms comparable to paclitaxel, including: (1) inhibition of tumor cell proliferation, (2) blockage of tumor cell in G2/M phase & (3) induction of b-tubulin polymerization.

In this trial, patient were administered the dry before surgery. At the time of surgery, specimens were collected and analyzed for drug concentrations.

The results indicated in Phase I were that the drug was safe. However, efficacy was not demonstrated later in a phase III trial.

Investigator Initiated Projects

06/2015-Present TH302 Plus radiation therapy for Malignant Meningioma, This is a basic science research project investigation TH302 ( nitrogen mustard) in combination with external beam radiation for the treatment of malignant meningioma. This study utilizes patient derived cell lines (from surgery) in an animal model. The preliminary results show significantly improved survival in mouse models where subjects receive TH302 + external be a radiation vs radiation alone. A manuscript is in preparation.

06/2015-Present Unidirectional Wafer for local delivery of chemotherapy in malignant brain, IACUC# 15102x : This basic science project involves he development of a novel wafer for implantation and unidirectional delivery of chemotherapy for malignant brain tumors. I have a patient pending regarding the chemical composition of the wafer. Preliminary studies regarding the dissolution of chemical in mouse brain models pending. This is ongoing study.


Awards & Accomplishments:

Carl Raba Family Chair in Neuro-Oncology: in April 2013 – I was Honored by being the first and only faculty member in the Department of Neurosurgery to be awarded an Endowed Chair by an enormously generous benefactor.

2 Neurosurgical Teaching Award 2012: Voted Best Teaching Award in 2012 by the Neurosurgical Resident House Staff

40 Under 40 Award: San Antonio Business Journal

Postdoctoral Ruth L. Kirschstein National Research Service Award: Research award

Magna Cum Laude: Medical School Graduation Honors

Alpha Omega Alpha: Medical Honor Society

Madison County Merit Scholar: Medical School Scholarship

University of Alabama School of Medicine Merit Scholar: Medical School Scholarship

06/1995 Summa Cum Laude: Undergraduate Honors


Professional Affiliations:

Dr. Floyd is the Program Director for Carl Raba Family Chair Neuro-Oncology.


Publications

(‘*’ indicates Peer Reviewed)

Abstract

1. Floyd JR. Keeler ER, Euscher ED, McCutcheon IE. Catamenial Sciatica: Mechanism and Proposed Management Algorithm 2010 Feb. (AANS/CNS Section on Disorders of the Spine and Peripheral Nerves).

Journal Article

* 1. Fountzilas C, Chang K, Hernandez B, Michalek J, Crownover R, Floyd J, Mahalingam D. Clinical characteristics and tratment outcomes of patients with colorectal cancer who develop brain metastasis: a single institution experience J Gastrointest Oncol 2017 Feb;8(1):55-63.

* 2. Narayanasamy G, Stathakis S, Gutierrez AN, Pappas E, Crownover R, Floyd JR, Papanikolaou N.. A Systematic Analysis of 2 Monoisocentric Techniques for the Treatment of Multiple Brain Metastases. Technol Cancer Res Treat. 2016 Sep:1-6.

* 3. Brown AF, Fan H, Floyd JR, Henry JM, Higgins RA. Primary Central Nervous System Histiocytic Sarcoma Arising After Precursor B-Cell Acute Lymphoblastic Leukemia. J Neuropathol Exp Neurol 2015 Dec;74(12):1120-1126.

* 4. Gruslova A, , Miller JR, Cavazos DA, Breirbart E, Bangio L, Yakov N, Soundararajan,Floyd JR,Brenner AJ. VB-111 : a novel anti-vascular therapeutic for glioblastoma multiforme Journal of Neuro-Oncology 2015 Sep;124(3):365-372.

* 5. Son C, Samples D, Brenner AJ, Floyd JR. Osteolytic calvarial lesions as initial presentation of latent neurosyphilis J Clin Neurosci 2015 May;22(5):909-910.

* 6. Floyd JR, Keeler ER, Euscher ED, McCutcheon IE. Cyclic sciatica from extrapelvic endometriosis affecting the sciatic nerve. J Neurosurg Spine 2011 Feb;14(2):281-289.

7. Floyd JR, A. Cmelak, P. Russell, K.D. Weaver. Endoscopic, Image-Guided, Transnasal Instillation of 32p for Recurrent Infrachiasmatic Cystic Craniopharyngioma Minimal Invasive Neurosurgery 2009;52:137-140.

* 8. Johnson MD, Floyd J, Caprioli RM. Proteomics in Diagnostic Neuropathology. J Neuropathol Exp Neurol 2006 Sep;65(9):837-845.

Not Specified

* 1. Floyd JR, Cmelak A, Russell P, Weaver KD. Endoscopic, image-guided, transnasal instillation of (32)P for recurrent infrachiasmatic cystic craniopharyngioma. Minim Invasive Neurosurg 2009 Jun;52(3):137-140.

Papers Submitted

* 1. Henry JM, Floyd John, Son Colin,. Metastatic Lymphoma Mimicking Pituitary Adenoma: A Case Report and Review of the Literature (CEN-2014-12-CR-1341) Journal of Neurological Surgery

* 2. Floyd JR, Carr, Kevin, McDougall, Ian, Henry JM, Brenner AJ, Booher, Grant. Glioblastoma Multiforme metastatic to the conus medullares Journal of Neurosurgery

* 3. Floyd JR, McGinnity, M, Rodriguez, J. Surgical evacuation of acute subdural hematoma in octogenarian: A ten-year experience from a single trauma center British Journal of Neurosurgery

4. Floyd JR, McGinnity, M, McGinnity, J, Zhang, F. Implant Compositions for the Unidirectional Delivery of Anticancer Compounds to the Brain Drug Development and Industrial Pharmacy