Statement from Clearity's Scientific Director, Dr. Deborah Zajchowski
Clearity is committed to helping patients identify drugs that have the highest likelihood of successfully treating their disease based on their tumor's molecular profile. Clearity's standard panel of molecular tests helps patients select from the approved cancer drugs that are nearly all cytotoxic chemotherapies. Recently, we expanded the panel to identify alterations in 180+ genes that are predicted to make tumors responsive to new therapies being tested in clinical trials. The combined information from the standard and expanded Clearity Panels allows patients to find out if their tumors could be sensitive to a clinical trial drug or to a combination of a chemotherapy drug with a clinical trial drug.
In a previous newsletter, I promised that we would write a series of articles explaining why we believe that it is important for patients to participate in clinical trials as soon as they are diagnosed and for caregivers and advocates to help with this process. Clinical trials are research studies in which the safety and effectiveness of a cancer drug are evaluated in people. There are different phases to this process - from the earliest phase I, where the least is known about the drug (dose and safety are figured out here) and the last, phase III, where prior evidence of effectiveness gets tested more rigorously to prove that the agent is successful. (See below for more details). In subsequent articles, we will discuss - the risks and benefits of participating in a clinical trial,
- why clinical trials should not be viewed as a last resort,
- how eligibility for some clinical trials can be a major factor in limiting options,
- how biomarkers have improved the clinical trial process by monitoring effects of drugs as well as matching drugs to patients,
- how the latest advances in our understanding about specific molecular drivers in ovarian cancer can be leveraged by using the profile to select drugs that target those drivers.
We look forward to helping Clearity patients and their doctors identify treatments that best match their tumor molecular profile, whether those treatments be approved cancer drugs or new therapies currently in clinical trials.
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 Clinical Trials for Ovarian Cancer Patients: Why Now?
by Cory Bentley, PhD and Teresa Gallagher, PhD
Ovarian cancer is a very diverse disease on the molecular level. Different tumors have different key molecular players and potentially different Achilles' heels. Researchers are making real progress in pinpointing key players involved in this disease, spurring the movement of new drugs into the clinic that target these newly identified players. For example, a 2011 study by The Cancer Genome Atlas (TCGA) research consortium found that ~35% of ovarian cancers have alterations in a molecular pathway known as PI3K/AKT. This pathway is important in cancer cell growth. New drugs targeting this pathway have entered clinic trials for ovarian cancer patients (e.g. MK-2206, which targets AKT and BYL719, which targets PI3K).
"This is cutting edge science," says Dr. Evan Friend, who volunteers with Clearity to evaluate clinical trial data. Dr. Friend points out that if an ovarian cancer patient's tumor suggests that her cancer may be responsive to a clinical trial drug, it gives her more treatment options that may lead to remission. "Although these drugs are new, there is a foundation of research supporting their clinical evaluation." Drugs that progress into clinical trials have already been thoroughly evaluated and tested in the laboratory and in animal models. By considering clinical trial drugs in addition to already approved drugs, more opportunities open for ovarian cancer patients to tailor their treatments to match their molecular profiles. This approach of matching treatment options to the patient's molecular profile defines personalized medicine.
Continuing progress in understanding molecular drivers in cancer, combined with significant technological advances in evaluating the associated molecular profiles, provide new opportunities for ovarian cancer patients to personalize their treatments. Foundation Medicine is leveraging these cutting edge advancements, so-called next-generation sequencing, to perform genomic analysis to detect alterations in relevant cancer genes. While Clearity's standard profile is focused on markers relevant to approved drugs, the genomic information that is obtained by sequencing a more expansive set of genes may have implications for drugs in clinical trials. Ovarian cancer molecular profiling from both panels provides the most comprehensive molecular profile available for ovarian cancer patients to date. The best-tailored fit may be from already approved drugs or may be from drugs just now making their way through clinical trials or from a combination chemotherapy-clinical trial drug based on the individual tumor profile.
There are currently 235 ongoing clinical trials for ovarian cancer in the United States. Approximately 25% of these are testing drugs that target specific proteins and pathways that have been shown to be active in pre-clinical ovarian cancer models. More drugs will continue to enter clinical trials, increasing the opportunities and options for ovarian cancer patients.
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Clinical Trial FAQs: 
In this and future newsletters, Clearity will try to answers patients' questions about participation in clinical trials. If you have questions, please send them to us and we will make every attempt to answer them in Clearity's future Clinical Trial FAQs.
Am I just a "guinea pig"? Will this drug work?
The study drug may be ineffective or it may not work for you personally. But in order for a drug to make it to human trials, there is a substantial body of scientific evidence that the drug has efficacy in animal models and that the rationale for use in humans is very strong. The more advanced it is in the clinical trial process, the more will be known about the safety and likely effectiveness of the drug.
How safe are clinical trial drugs? Are the side effects known?
All drugs have side effects including those in clinical trials. The clinical trial drugs can have unknown and serious side effects, but safety is extremely important. The clinical trial process includes several mechanisms designed to ensure the safety of the patient, including careful oversight by physicians, scientists, and expert committees and careful monitoring of the patient for side effects. Your physician and/or the physician leading the trial will evaluate you very closely for any adverse effects of the trial drug. If this is the first time a drug is ever being used in a human (as in a phase I trial), the trial drug dosage will be very small. If the low dose is tolerated, the trial drug dosage will be increased incrementally.
What is the placebo arm?
In some clinical trials, not all patients receive the clinical trial drug. This is the placebo arm or group that receives only the standard-of-care regimen. These trials compare the response of patients in the placebo arm who receive the standard of care (usually one or two approved drugs) with patients in the study arm who receive the same standard care with the clinical trial drug also added to the treatment regimen.
Clearity will help patients and their doctors find a trial that expands potential options rather than limiting them. This means that the placebo arm is not a "bad" option for the patient because she will be treated with an approved drug or drugs (that are matched to her tumor profile) and will have the added benefit that she may also be treated with a new drug. That new drug can also match her tumor's molecular profile.
Who pays for clinical trials?
There are patient care costs and research costs associated with clinical trials. Generally the patient's insurance continues to cover the patient care costs associated with treating cancer. The clinical trial sponsor will cover the cost of the study drug and any additional tests related to the clinical trial. The patient will know in advance who is responsible for what costs so there should be no surprises.
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 Clinical Trial Phases:  A Recap from our May 2010 Patient Newsletter
Phase I
-Tests the safety of the drug
-All volunteers are given the drug. There is no placebo group. These are dose escalating studies, meaning that the first patients receive the lowest dose of the drug. If there are no adverse reactions, the next group of patients will receive a higher dose and so on. Patients will also be monitored for tumor response.
-One to three locations involved.
-Twenty to 80 volunteers.
Phase II
-Tests for efficacy (effect on cancer growth or recurrence) and the dosing requirements for efficacy
-There may or not be a placebo control group. The placebo group is not given the active drug, but rather an inert look-alike to control for effects not related to the active drug. The trial will specify whether or not there is a placebo group.
-There are usually several locations involved. The precise locations for each clinical trial are listed on NIH's website: www.clinicaltrials.gov.
-One hundred to 300 volunteers
Phase III
-The definitive assessment of the effectiveness of a drug
-This trial will have a placebo control group. These studies are double blind-- meaning that neither the patient nor the doctor knows if the drug is active or a placebo.
-Several hundred locations may be involved.
-One thousand to 3000 volunteers
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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.
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