Peer Perspectives in Oncology
In Peer Perspectives in Oncology, Medelis brings together some of the industry’s most respected researchers to talk about the issues facing Chief Medical Officers today. They’re issues we all face on a daily basis: Rising costs. Optimum patient accrual. Targeted therapeutics. Patient safety. FDA regulations. Efficacy. Budgets. Timelines.
In this Q&A series, we’ll discuss these challenges with leading experts who deliver practical, frontline insights gleaned from years of experience bringing new drugs to market.
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Adaptive Trial Design in Phase I, Phase II Studies
Published February 2, 2010
Adaptive trial design is a hot issue in the drug development community. Adaptive conferences and web seminars abound, and suddenly, every consultant or vendor to the industry has become an adaptive expert. The FDA and EMEA are also much more receptive to adaptive trials than they were a few years ago.
However, the picture is different from what the industry had expected. Originally, much of the focus was on adaptive phase III trials as well as on seamless phase II/III trials. Those are, indeed, successfully being implemented today. But the real action is in phase II dose-finding trials and even in phase I trials for safety.
In this issue of Peer Perspectives in Oncology, Medelis talks with Ranganath Nayak, PhD., the CEO of Cytel, Inc., about the benefits, opportunities, and challenges presented by adaptive trial design in phase I and phase II studies.
To download the interview, please fill out the form at right. »
Context of Vulnerability: A Powerful New Paradigm for Targeted Drug Development
Published February 17, 2009
Renowned cancer researcher Dr. Daniel Von Hoff and his team at TGen are fervent believers in a new approach to developing novel therapies for patients with pancreatic cancer. They are guided by a rationale dubbed the "context of vulnerability." Dr. Von Hoff provides case studies and explains how this powerful paradigm has already led to promising discoveries and is changing the future of oncology drug development.
"People say we have lost the war on cancer and it is so discouraging to the people who deliver the care every day, the people who are seeing those curves turn around," laments Dr. Von Hoff. "The fact is that the rising tide of cancer deaths hasn’t just been stemmed – it’s been turned around. Mortality, in terms of absolute number of deaths, has been down for two years in a row. It should have been going up like a rocket because we’re all aging."
Dr. Von Hoff’s team believes a new approach for targeted drug development is the key to developing powerful targeted therapeutics. He advocates heavily for "context of vulnerability," a term coined by TGen's Spryo Mousses, Ph.D. It refers to the genetic configuration in a patient’s tumor that makes it susceptible to a specific drug.
"If you let context of vulnerability guide drug development, you would put only those patients who have the appropriate susceptibility to the drug on trial," he explains. "This optimizes your chance of seeing efficacy with a much smaller n. It’s essentially how Herceptin® got approved with an n of 480. If they hadn’t pre-selected patients for the context of vulnerability, estimates say that it would have taken about 23,000 patients to get the drug approved."
In the abstract, Dr. Von Hoff provides a detailed look at the promise and potential of "context of vulnerability" and the opportunity it creates in the war on cancer:
- How context of vulnerability provides a genetic rationale for a targeted therapy;
- How to establish a patient’s context of vulnerability;
- How using context of vulnerability to guide drug development can improve your chance of seeing efficacy with a much smaller n;
- Incorporating context of vulnerability as the oncologist’s "sixth vital sign;"
- A case study of context of vulnerability in use and how it improves patient care and new agent development;
- The gap between known contexts of vulnerability and available therapeutics;
- How CMOs can flip their drug development planning to leverage this approach;
- Feedback from the FDA, national and international groups;
- The promise and potential of this approach;
- Targeted therapeutics and the future of oncology.
Read the abstract online, or you can download it as a PDF -- just fill out the form here and we'll email you a link.
The Lost Opportunity in Phase I Oncology Trials
Published December 22, 2008
Cancer drug developers traditionally use the phase I trial solely to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of a drug. Renowned oncology investigator Daniel D. Von Hoff, M.D. advocates for a phase I approach that looks beyond toxicity and gleans meaningful efficacy data, creating a more compelling rationale for further investment and improved patient care.
"A CMO [Chief Medical Officer] looking at the phase I typically sees it as a toxicity trial, not a therapeutic trial, because of course it is not randomized," Dr. Von Hoff explains. “But we - doctors at the bedside and the patients themselves - do not see it that way. We are looking for an improvement and survival.”
In this issue, Dr. Von Hoff explains what Dr. Bob Temple at the FDA called a "lost art" in drug development: measuring a tumor’s “time to progression” on the current drug versus the tumor’s “time to progression” on the patient’s previous treatment. He answers questions including
- The distinction between “time on therapy” and “time to progression”
- Why CMOs should place greater value on this data
- Why the practice isn’t more common
- How to leverage the clinical investigator’s observations and clinical judgment in the analysis of a treatment
- Why the subjective nature of this approach benefits patients and drug developers alike
- Why time to progression should be included in the trial protocol so it becomes part of each patient’s data bank
- How to appropriately incorporate efficacy into the story you tell to sponsors and investors when raising money
- When to invest more deeply in a new therapy based on this data.
Read the abstract online, or you can download it as a PDF -- just fill out the form here and we'll email you a link.
Preclinical Trials: A Nuanced Approach to Get Into the Clinic Faster
Published September 4, 2008
Oncology preclinical studies are commonly viewed as straightforward investigations run exclusively by researchers. Tasked with finding therapeutic interventions that stop cell growth, researchers often operate independently without true integration with the preclinical, regulatory and clinical teams.
In this issue, Dr. Mike McGarry, VP of Preclinical Studies at Medelis, describes a more nuanced preclinical process that can help a Chief Medical Officer (CMO) get into the clinic faster. This approach hinges on a strategic, well-defined rodent model, quality data, and ongoing integration between the preclinical, regulatory and clinical teams.
Dr. McGarry provides a detailed inside look at the issues that can speed or derail the preclinical phase:
- Critical factors for a CMO to understand and evaluate during this step in the drug development process
- Regulatory assessments and how to avoid hitting a preclinical wall
- The nuances and complexities of animal models, tumor selection, and other variables
- How to keep the preclinical, regulatory and clinical teams involved in feasibility dialogue
- The typical preclinical process and the questions a CMO should be asking at each step
- Additional requirements unique to oncology preclinical trials
- What to look for in an outside preclinical team.
Read the abstract online, or you can download it as a PDF -- just fill out the form here and we'll email you a link.
The Complete Phase Ib: An Approach for Getting to Phase II Faster
Published July 9, 2008
In this interview, renowned oncology researcher Daniel D. Von Hoff, M.D. discusses “the complete phase Ib,” a trial design that streamlines phase I by testing various drug combinations in one trial with multiple arms running in parallel. This structure creates rapid accrual rates, substantial economies of scale and significant time savings for sponsors versus the traditional sequential approach. It also garners enthusiasm from investigators and patients, who ultimately gain greater potential for improved therapeutic benefits and care.
Dr. Von Hoff provides insight and details on a variety of questions about this approach:
- "The complete phase Ib" concept
- Patient accrual and treatment benefits
- How the approach can "rescue" patients
- Dosing strategies
- Logistical considerations
- Cost and timing considerations
- Effects on phase II studies
- Reactions from the FDA, investigators, sponsors and patients.
Read the abstract online, or you can download it as a PDF -- just fill out the form here and we'll email you a link.
Patient Safety in Clinical Trials:
A Q&A with James T. Gourzis, M.D., Ph.D.
Published March 25, 2008
Clinical investigators are responsible for protecting the rights, safety, and welfare of subjects under their care during a clinical trial (21 CFR 312.60 and 812.100). In many trials, the sponsor delegates some decisions regarding trial design and conduct to an entity such as a steering committee or contract research organization (CRO).
Patient safety has always been the industry’s focus during clinical trials. However, a recent spate of well-publicized patient safety issues have increased public scrutiny and the industry’s desire to improve study quality, resulting in larger, longer, more expensive trials.
In this issue, James T. Gourzis, M.D., Ph.D., talks with Medelis about issues affecting patient safety:
- Factors that have launched patient safety to the forefront of public scrutiny, including the effects of increased reporting requirements
- What to look for when evaluating CRO excellence and commitment to patient safety
- Unique safety considerations in oncology trials and the ramifications of the rare toxicity
- Optimizing the role of the Data Monitoring Committee
- Budget decisions that support patient safety
- The evolution and future of FDA regulations.
Read the abstract online, or you can download it as a PDF -- just fill out the form here and we'll email you a link.
