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Survivor Newsletter
May 2013
Introduction from Clearity's Scientific Director, Dr. Deborah Zajchowski
Clearity's mission is to improve survival for women battling ovarian cancer by helping patients and their physicians make more informed treatment decisions based on their tumor's molecular profile. Our standard profile can be used to inform decisions about chemotherapy drugs as well as drugs that are in clinical trials. 
By expanding this profile to include the sequencing of 236 genes, additional clinical trial drug matches can be identified.   Through our conversations with patients, we discovered that there are questions, concerns, and even some misunderstanding about clinical trials.  We have created a series of newsletter articles that we hope will take some of the mystery out of the clinical trials process so that patients can take full advantage of the opportunities that they provide.   Our first newsletter introduced the clinical trial process and can be viewed here.
In this newsletter, Drs Bentley and Gallagher discuss some of the major concerns about clinical trial participation and highlight results from a recent phase 1 trial of a novel antibody-cytotoxic drug conjugate that targets CA125 on tumor cells as a way to describe what can be expected in that early stage testing of a new drug.  We look forward to hearing your feedback.
Treatment Choices and Clinical Trials
by Cory Bentley, PhD and Teresa Gallagher, PhD 


A study presented at the Society of Gynecological Oncology meeting found that most women diagnosed with ovarian cancer are not receiving medical care that meets the guidelines of the National Comprehensive Cancer Network (NCCN). The study was presented in April by Dr. Robert Bristow of the University of California, Irvine and reviewed the medical records of more than 13,000 women with ovarian cancer. Surprisingly, the study found that only 37 percent of women were receiving the recommended standard of care. Importantly, the advanced stage patients who received the standard of care recommended by the NCCN guidelines lived longer than those who did not. Women treated by physicians with less experience treating ovarian cancer (those treating fewer than 10 cases per year) and women treated at "low-volume" hospitals (those treating fewer than 20 patients with ovarian cancer each year) were less likely to receive the standard of care. 


Faced with such a challenging environment, it is no wonder that many patients can be overwhelmed and even skeptical. At Clearity, we believe that one way to inform treatment selection is to use the results of tumor molecular profiling to help prioritize drugs among those recommended in the NCCN guidelines for recurrent ovarian cancer. Tumor profile reports can also be used to help select a drug or drug combination from among those that are currently in clinical trials. 

When it comes to clinical trials, patients can have many

reservations. Dr. Teresa Gallagher has studied how patients consider clinical trial options. She explains that there are several important barriers that may deter women from deciding to participate in a clinical trial:

  1. Concern about being used as a "human guinea pig" to test potentially unsafe drugs; 
  2. Mistrust of the drug companies and their motives; 
  3. Fear of being assigned to a group where you will not receive the experimental treatment; 
  4. Belief that you will not benefit from the trial drug -- that currently available treatments are more effective than "experimental" treatments; 
  5. Lack of awareness of appropriate trials that fit your molecular profile and other circumstances such as no available trials nearby and eligibility criteria. 

With all these questions and concerns, why would a patient consider a clinical trial? This question was put to Clearity's scientific director, Deb Zajchowski, PhD. According to Dr. Zajchowski, one compelling reason for participation in a clinical trial is the possibility of receiving a drug that could be a very effective treatment. "Many of the drugs that are now in clinical trials are predicted to work only in certain patients who can be identified by tumor molecular profiling approaches similar to those used by Clearity. It is hoped that by such selection, these new drugs will work in more patients than in the past when there was no selection process."


To those patients whose top concern is whether or not they receive the trial drug, Dr Zajchowski points out that randomized clinical trials compare a standard treatment with the same treatment with a new study drug added on top. Therefore, the patient who is in the placebo arm will still receive the standard treatment that is appropriate for her cancer. The clinical trial drug is in addition to the standard of care. A clinical trial makes a lot of sense for a patient when her molecular profile has matched her to the standard of care drug used in the trial as well as the new drug being tested. 


Another factor keeping women from participating in clinical trials is a concern about safety. Safety issues are most pertinent for a phase I study, which is designed to evaluate the safety of a drug being used in human beings for the first time. Several aspects of a phase I study design help keep patients safe. First, substantial data is available on the safety of the drug in animal models; second, patients are very closely monitored; third, the study starts with a very low dose and only increases to a higher dose after the lower dose proves tolerable; and lastly, a patient can withdraw from a trial at any time (read about DMUC5754A phase I trial below) There is always a risk of experiencing side effects with a clinical trial drug, but Dr. Zajchowski explains, "The decision is a personal one where every patient must balance the risks with the possible benefits-- the chance of receiving a new drug that could work better than any other drug to treat your cancer and the risk for a severe adverse reaction." Both drug effectiveness and safety are critical to the success of any drug. 


Suspicion of drug companies' motivations dissuades some patients from participating in clinical trials. Dr. Teresa Gallagher explains that unfortunately the pharmaceutical industry is being portrayed negatively in the media, which can cause patients to mistrust the drug companies and drug trials. Cory Bentley, PhD, the author of this article, currently works in drug discovery and development for a biotechnology company, where real people are interested in making a real difference. In Dr. Bentley's experience, people in drug companies and physicians running clinical trials are working to make a drug that will truly give something valuable to patients: extended life and quality of life. 


As patients look at clinical trials, there are so many issues to consider. Perhaps the most critical considerations are how well a trial drug matches her tumor molecular profile and practical concerns such as eligibility and distance from home. Clearity will help patients find their way to a treatment that best fits their molecular profile, whether that includes a trial drug or approved drug. 


Let Clearity know what you think about clinical trials. 
Send your feedback and questions to 
Dr. Cory Bentley, 


CA125 becomes a target for destruction 
of ovarian cancer by phase I drug
by Cory Bentley, PhD
Most ovarian cancer patients have become familiar with CA125 blood level monitoring, but trial drug DMUC5754A from Genentech puts a new twist on this familiar blood marker of advanced ovarian cancer. CA125 (cancer antigen 125) also goes by the name mucin 16, Muc16 for short. Muc16 is overexpressed on the cell surface of most ovarian cancers compared to normal tissue. So while Muc16 in the blood may be a biomarker for ovarian cancer, on the tumor cell surface it targets the cell for destruction by DMUC5754A. 


DMUC1DMUC5754A is a so-called therapeutic antibody that specifically binds to Muc16. It is much like the antibodies that one's body naturally makes to fight off infection and invaders. DMUC5754A is also an armed antibody by its linkage to a highly toxic drug, MMAE (monomethyl auristatin E). An armed antibody is known as an ADC - antibody drug conjugate. 


Phase I clinical trial data for ADC DMUC5754A were presented at this year's American Association for Cancer Research (AACR) Annual Meeting in April. This phase I study evaluated several aspects of this drug in advanced recurrent platinum-resistant ovarian cancer, including safety and activity. This phase 1 trial had two parts; first, dose escalation to determine the maximum tolerated dose (MTD) and then expansion for further analysis at the MTD. Dose escalation design starts patients on a very low dose of the drug. These patients are closely monitored for side effects. If side effects are mild, the next group of patients receives a higher dose of the drug. Dose escalation continues in successive groups of patients until strong side effects are observed in greater than 30% of patients, establishing the MTD for DMUC5754A. The expansion part of the trial involved 22 more patients at this highest dose to test for potential efficacy and confirm the safety. 


Of the 29 patients treated at the MTD, one complete response was observed (no evidence of cancer after treatment) and 4 partial responses were observed (decreased tumor size). All responses were seen in patients whose tumors expressed moderate to high levels of the targeted protein Muc16, suggesting that using Muc-16 expression on tumor cells will help to identify responsive patients in the future. Dr. Joyce Liu, who presented the phase I study, concluded that DMUC5754A "has an encouraging safety profile and evidence of anti-tumor activity in MUC16-expressing ovarian cancer." 


Finding responders in this group of patients is not a small feat. Patients in this study were heavily pre-treated, averaging 4 prior therapies, and platinum-resistant. This study exemplifies why clinical trials bring true hope to ovarian cancer patients. Although DMUC5754A must still prove its value in phase II and III trials, results from this phase I trial are hopeful.  
The information included in this newsletter is for educational purposes only. It is not intended nor implied that this information be a substitute for professional medical advice. You should always consult your healthcare provider to determine the appropriateness of the information for your own situation.