The US Department of Defense had an opportunity last month to show taxpayers what they get for their money, specifically the millions of dollars the Congressionally Directed Medical Research Programs awarded and managed by the DoD for prostate cancer research.
The first IMPaCT (Innovative Minds in Prostate Cancer Today) meeting took place in Atlanta a decade after Congress began investing its own funds in prostate cancer research in the Prostate Cancer Research Program.
The meeting highlighted basic and clinical research funded by Congress through the DoD and aimed at preventing, detecting, and treating prostate cancer.
When the Prostate Cancer Research Program was first funded in 1997, the Department of Defense already had experience in managing Congressional Directed Medical Research Program funds in breast cancer research programs. Today, besides breast and prostate cancer, the DoD also awards and manages Congressionally Directed funds for research in ovarian cancer, chronic myelogenous leukemia, neurofibromatosis, and tuberous sclerosis complex.
The Prostate Cancer Research Program is now the second leading source of extramural prostate cancer research funding in the United States—after the National Cancer Institute—with $80 million awarded in the latest fiscal year and $730 million between fiscal years 1997 and 2006 (http://cdmrp.army.mil/pcrp/default.htm).
“IMPaCT is a report to the American public about how we have invested these dollars, and about some of the outcomes that have come from our investment,” said Col. Janet R. Harris, RN, PhD, US Army Nurse Corps, the Program's Director since 2005.
The Deputy Director, Capt. Melissa Kaime, a hematologist/oncologist in the US Navy Medical Corps, said the Program has distributed approximately 1,500 individual grants aimed at detecting and treating prostate cancer.
The four-day IMPaCT meeting highlighted the latest data from its funded studies on health disparities among ethnicities and social classes, stem cells, treatment and mortality trends, diet and lifestyle choices, and new drugs.
One area highlighted at IMPaCT is a prostate cancer program studying the health disparity between African Americans and Caucasians, as well as between African Americans from different states.
An intriguing finding from researchers in a health disparity consortium led by James Mohler, MD, now Chair of Urologic Oncology at Roswell Park Cancer Institute, is that while African Americans in North Carolina have a very high mortality rate from prostate cancer, African Americans from Louisiana actually have a much lower mortality rate from the disease, although it is still higher than the rate for Caucasians there.
Col. Harris said the hope is that studies such as this will help researchers tease out what is contributing to this disparity in the African American community.
Clinical Trials Consortium
A new collaborative research organization was formed within the Prostate Cancer Research Program last year to fit a special niche, that of expediting trials for early drug development and for screening the effectiveness of drugs prior to large, Phase III trials.
The Prostate Cancer Clinical Trials Consortium (PCCTC) is led by Howard I. Scher, MD, Chief of the Genitourinary Oncology Service and Chair in Urologic Oncology at Memorial Sloan-Kettering Cancer Center, and includes 10 U.S. academic research centers.
The consortium was created as a response to a major impediment in rapid evaluation of new therapies for prostate cancer—the lack of sufficient resources to support the infrastructure needed to conduct Phase I/II and Phase II clinical trials in prostate cancer.
“Creating a common infrastructure across institutions to implement multi-institutional trials presents challenges, but the experience of the PCCTC is encouraging for other groups that want to establish an infrastructure that will advance research in their fields,” Dr. Scher wrote in a statement describing the consortium. “To date, such consortia are uncommon because traditional trial funding mechanisms account for costs on a per-trial, per-patient, or per-agent basis.”
By the time of the IMPaCT meeting the consortium had accrued 366 patients into 26 Phase I/II and Phase II trials.
Two prostate cancer researchers involved in ongoing consortium studies discussed the consortium in telephone interviews from the IMPaCT meeting.
‘Group Effort Based on Progressive Communication’
Christopher J. Logothetis, MD, Professor and Chair of Genitourinary Medical Oncology at the University of Texas M. D. Anderson Cancer Center, described the consortium as a group effort based on progressive communication between groups.
“Consortium studies do not address cost effectiveness, toxicity profile, or the measure of benefit of new drugs,” he said. “Rather it is walking through that difficult transition after biological concept and early drugs, and before huge investments in Phase III trials.”
Consortium programs are also designed to give investigators a sense of how a new drug or treatment fits in the spectrum of other tools available to help patients, Dr. Logothetis said, explaining that this differs from studies with a very narrow focus, such as those defined by pharmaceutical companies during drug development.
Dr. Logothetis added that within the consortium there is a strong sense that there is no such thing as an uninformative or failed trial. “Typically a drug either succeeds or fails, but from our perspective, knowing why a drug has not worked will avoid repetition of that error in the future.”
‘Best Minds in the Country in a Single Team’
Dr. Logothetis and Tomasz M. Beer, MD, Chair and Director of Prostate Cancer Research at Oregon Health & Science University (OHSU), were among the authors of a Phase I study presented at the IMPaCT meeting on the use of sunitinib in combination with docetaxel and prednisone in patients with metastatic “castrate-resistant” prostate cancer.
Along with Neal D. Shore, MD, the first author, the researchers reported that sunitinib in combination with docetaxel and prednisone appears to be a safe and well-tolerated regimen in these patients. A Phase II study of the combination will be underway shortly, the authors said.
Dr. Beer, who is also Section Head of Solid Tumor Oncology and Associate Professor of Medicine at OHSU, said the sunitinib study is one of approximately 12 ongoing consortium studies at the institution. He estimated that OHSU receives $200,000 to $300,000 through the prostate cancer consortium.
Dr. Beer said he is impressed that “this consortium has a very strong mechanism for making sure that studies are done right the first time—You'd be amazed how often we fall down in research when we rush into a study design that doesn't exactly answer the question as well as it should be answered.”
He said collaboration among the consortium members is a must, “because we are evaluated in this grant specifically on metrics of how well we collaborate with one another, and how that translates into progress against prostate cancer.
“And it's incredibly rewarding to be able to work with the best minds in the country in a single team,” Dr. Beer said.
Different from Cooperative Trial Group
Although the sunitinib study and many others within the consortium involve clinical trials, Dr. Beer said the consortium is different from a cooperative clinical-trials group.
“Those groups might include predominantly patient-care oriented sites that are able to put patients on clinical trials but that do not have strong laboratory capabilities,” he explained. “A cooperative group's strength is in its ability to carry out large, randomized national studies with thousands of patients, the final step in developing a new treatment.
“This consortium, on the other hand, includes only sites that have a very ‘deep bench’ in the lab, that are generating the ideas and doing initial evaluation, and that can move things straight out of the lab and into patients.
“This is where ideas are born and geminate and undergo initial evaluation.”
Consumer Advocates Have Their Say
A strong, national grassroots effort led by the breast cancer advocacy community helped create the Congressional Directed Medical Research Program in 1993. Since then, consumer advocates have participated in setting the Program's priorities and making funding decisions.
Some 700 consumer advocates have now served on peer and program-review panels for basic science and public health, according to the 2006 annual report.
Consumer reviewers selected are cancer survivors active in advocacy, outreach, or support organization in their local communities.
One of the reviewers, Charles “Chuck” Maack, has been a consumer advocate on prostate cancer panels in 2006 and 2007. A 74-year-old Navy veteran, Mr. Maack underwent radical prostatectomy in 1992, and then radiation for locoregional involvement. Three years later, a rising PSA led to intermittent androgen-deprivation treatment. His PSA today is less than 2.0 ng/mL, but he knows he still has the disease.
Mr. Mack said that when the disease recurred after surgery, he joined the Wichita chapter of the national Us TOO organization because he felt he needed to know more about prostate cancer. A retired anesthesiologist in the group became his mentor, and as Mr. Maack learned more about the disease, other members started asking him for advice.
(See www.ustoowichita.org under “Observations” for articles he has authored or coauthored with a physician.)
In a phone interview from the meeting in Atlanta, Mr. Maack said that other members of Us TOO recommended him to the DoD program as a possible advocacy representative for the Prostate Cancer Research Program.
“In my first year, 2006, I was assigned to a panel on Cell Biology led by Ramesh Nayak, PhD, of the University of Arizona,” Mr. Maack said. He said he and the panel reviewed 17 grant proposals that year.
In 2007 Mr. Maack was on the Physical Imaging panel, a group that included 17 scientists and three consumer reviewers who reviewed 19 funding proposals.
He said he was initially daunted by the task when the background and review material arrived at his door “in big boxes,” but well before the three-day panel meetings.
“As consumer reviewers and laymen, we're not expected to understand everything that's going on [scientifically],” he said. The advocates' contributions are from what they have read, from what they've heard at other meetings, and from focusing on the question of how soon a proposed study will make a difference in prostate cancer.
“We get a chance to comment on each proposal, and then the entire panel decides which go on to higher level review panels,” he said.
Mr. Maack said it has been a very positive experience for him to be on these panels and to see how much is being done to fight prostate cancer—“and now I can also appreciate how complicated cancer biology is.”