Our Science – Arlen Website

Philip M. Arlen, M.D.

Laboratory of Tumor Immunology and Biology Senior Clinician 10 Center Drive, MSC 1750 Building 10, Room 5B52 Bethesda, MD 20892 Phone:   301-496-0629 Fax:   301-480-5094 E-Mail:   pa52s@nih.gov

Biography

Director, Clinical Research Group
Dr. Philip M. Arlen graduated from the Medical College of Georgia, School of Medicine in 1991. Following the completion of his fellowship training in Hematology/ Oncology at Emory University in 1997, he initially came to the NCI as a biotechnology fellow in the LTIB, CCR, NCI. He is currently a Senior Clinical/Scientific Investigator in the Laboratory of Tumor Immunology and Biology, Center for Cancer Research, NCI, and is the Director of the Clinical Research Group. Dr. Arlen is also a member of the senior medical staff at both the NCI Clinical Center and the National Naval Medical Center.

Research

Integration of Cancer Vaccines with Standard of Care Therapies
The specific aims of this Group are to conduct clinical trials (a) to evaluate the combined use of vaccines with hormones in patients with prostate cancer, (b) to define how to best use vaccines with standard of care chemotherapies, (c) in collaborative studies, to evaluate the use of vaccines in the transplant setting, and (d) to develop novel immunoassays to better define patients' immune responses to vaccine. Dr. Arlen has focused on the use of these novel immunotherapies and therapeutic strategies in patients with prostate and breast carcinomas.

As Director of the Clinical Research Group, LTIB, Dr. Arlen is responsible for integrating recent laboratory research findings with science-driven clinical trials. His major emphasis is the integration of cancer vaccines with chemotherapeutic agents and hormones in the treatment of human carcinomas. He works extremely closely with the research scientists in the LTIB in the design of preclinical studies toward the initiation and analyses of novel clinical trial designs.

A rapidly emerging population of prostate cancer patients are those who are hormone refractory with biochemical recurrence, i.e., patients with no measurable disease on scans but with a rising serum PSA level (D0.5 patients). Dr. Arlen has recently completed the first randomized clinical trial in this patient population. The trial successfully accrued 42 patients and the results were recently published. Patients were randomized to receive either second line anti-androgen treatment (nilutamide) or vaccine. The vaccine employed in this study consisted of rV-B7 admixed with rV-PSA with booster vaccines consisting of avipox rF-PSA. Patients in both arms had a cross-over at treatment failure to continue receiving both treatments. The median time to treatment failure was 7.6 months for nilutamide and 9.9 months for vaccine (i.e., no statistical difference). However, 12 of 21 patients in the vaccine arm who then received nilutamide in addition to vaccine had an additional median time to treatment failure of 13.9 months for a total of 25.9 months from the start of treatment. These studies have led to the planning and initial approvals for a randomized multi-center Phase III prostate cancer study as a joint collaboration with the Eastern Cooperative Oncology Group (ECOG) in this patient population. This study will employ PSA-TRICOM vaccines containing transgenes for three T-cell costimulatory molecules in patients with non-metastatic (by scan) hormone resistant (stage D0.5) prostate cancer with an endpoint of development of measurable disease on scan. To our knowledge this will be the first Phase III study sponsored by the NCI for a 'gene therapy'.

Dr. Arlen has also initiated a clinical study in metastatic prostate cancer patients employing PSA-TRICOM vaccines (rV-PSA-TRICOM prime and multiple rF-PSA-TRICOM boosts). Scientists in the LTIB have demonstrated, in preclinical models, that one administration of a fowlpox vector containing the gene for GM-CSF (rF-GM-CSF) is at least as efficient, if not more efficient, than four daily injections of recombinant GM-CSF protein in enhancing the localization of dendritic cells to regional nodes. Dr. Arlen has translated this concept into this clinical trial comparing, in randomized arms, patients receiving the PSA-TRICOM vaccines alone, with recombinant GM-CSF protein, and with rF-GM-CSF, evaluating both clinical responses and PSA-specific T-cell responses.

Dr. Arlen is also involved in studies to explore the strategy of combining chemotherapy with vaccine. He has recently completed a 28-patient study in androgen insensitive metastatic prostate cancer patients, examining the role of combining weekly docetaxel and decadron with a PSA-based pox vector vaccine (rV-PSA + rV-B7 primary vaccination followed by rF-PSA booster vaccinations). This study showed that patients receiving the combination of chemotherapy and vaccine were able to develop T- cell responses similar to those seen in patients receiving vaccine alone. Thus the chemotherapy did not suppress the ability of the patients to mount an immune response to the vaccine. This has now led to other trials employing poxvirus-based vaccines with docetaxel.

The Clinical Research Group plans to build upon these prior studies utilizing combinatorial therapy with hormones and chemotherapy with vaccines. Dr. Arlen is planning a randomized Phase II study at the NCI to confirm whether there is a clinical benefit for prostate cancer patients to receive the combination of hormones and vaccine as compared to hormones alone. Dr. Arlen has also designed a randomized clinical study at NCI in patients with metastatic breast cancer utilizing pox vector vaccines containing two tumor-associated antigens (CEA and MUC-1) and the three costimulatory molecules (TRICOM) in combination with weekly docetaxel therapy vs. docetaxel alone. In addition, Dr. Arlen has also developed a collaborative effort with investigators in the Experimental Transplant Investigation Branch, CCR, NCI. He is involved in the design of a clinical study examining the use of this vaccine in breast cancer patients undergoing allogeneic stem cell transplantation.

Dr. Arlen collaborates with Dr. James Gulley, M.D., Ph.D., Director, Clinical Trials Group, LTIB, CCR, NCI, as well as with Dr. William Dahut, head of the Genitourinary and Gynecologic Clinical Research Section, Medical Oncology Branch, CCR, NCI.

Clinical Research Protocols at the Center for Cancer Research, NIH

Dr. Arlen is P.I. or Protocol Chairman

IN PROGRESS:
A Randomized Pilot Phase II Study of Docetaxel Alone or in Combination with PANVAC-V (vaccinia) and PANVAC-F (fowlpox) in Patients with Metastatic Breast Cancer (NCI 05C-0229)P.I. - Philip M. Arlen, M.D., LTIB, MOB; Associate Investigators - James L. Gulley, M.D., Ph.D., LTIB, MOB; Sandra Swain, M.D., MOB, NCI

A Phase I-II Study of Tumor Vaccine Following Chemotherapy in Patients with Previously Untreated Metastatic Breast Cancer: Vaccine-Induced Bias of T-Cell Repertoire Reconstitution after T-Cell Re-Infusion (NCI 03-C-0040)
P.I. - Claude Sportes, M.D., MOB, NCI; Associate Investigators - Philip M. Arlen, M.D., LTIB, MOB; James L. Gulley, M.D., Ph.D., LTIB, MOB

A Randomized Phase II Trial Combining Vaccine Therapy with PROSTVAC/TRICOM and Flutamide, vs Flutamide Alone in Patients with Androgen Insensitive, Non Metastatic (D0.5) Prostate Cancer (NCI-07-C-0107)
P.I. - Philip M. Arlen, M.D., LTIB, MOB; Associate Investigators - James L. Gulley, M.D., Ph.D., LTIB, MOB; William Dahut, M.D., MOB, NCI

RECENTLY COMPLETED:
A Randomized Phase II Study of Either Immunotherapy with a Regimen of Recombinant Pox Viruses That Express PSA/B7.1 Plus Adjuvant GM-CSF and IL-2 or Hormone Therapy with Nilutamide in Patients with Hormone Refractory Prostate Cancer and No Radiographic Evidence of Disease (NCI 00-C-0137)
P.I. - Philip M. Arlen, M.D., LTIB, MOB; Associate Investigators - James L. Gulley, M.D., Ph.D., LTIB, MOB; William Dahut, M.D., MOB, NCI

A Pilot Trial of Pox Vector PSA Vaccine with Concurrent Docetaxel versus Pox Vector PSA Vaccine Followed by Docetaxel in Metastatic Androgen Independent Prostate Cancer (NCI 02-C-0218)
Protocol Chair - Philip M. Arlen, M.D., LTIB, MOB; P.I. - William Dahut, M.D., MOB, NCI; Associate Investigator - James L. Gulley, M.D., Ph.D., LTIB, MOB

A Phase I Pilot Study of Sequential Vaccinations with rFowlpox-PSA (L155) TRICOM (PROSTVAC-F/TRICOM) Alone or in Combination with rVaccinia-PSA (L155) TRICOM (PROSTVAC-V/TRICOM) and the Role of GM-CSF, in Patients with Prostate Cancer (NCI 03-C-0176A)
P.I. - Philip M. Arlen, M.D., LTIB, MOB; Protocol Chair - James L. Gulley, M.D., Ph.D., LTIB, MOB; Associate Investigator - William Dahut, M.D., MOB, NCI

A Phase II Study of Sequential Vaccinations with rFowlpox-PSA (L155) TRICOM (PROSTVAC-F/TRICOM) Alone or in Combination with rVaccinia-PSA (L155) TRICOM (PROSTVAC-V/TRICOM) and the Role of GM-CSF, in Patients with Prostate Cancer (NCI 03-C-0176B)
P.I. - Philip M. Arlen, M.D., LTIB, MOB; Protocol Chair - James L. Gulley, M.D., Ph.D., LTIB, MOB; Associate Investigator - William Dahut, M.D., MOB, NCI


For a list of publications from the Clinical Trials Group see 'Links'.

This page was last updated on 9/8/2008.