A primary goal of cancer clinical trials at SCOR member site Lee Health Cancer Center is to make sure patients have access to as many treatment options as possible while keeping them close to home. Lee Health research nurse Alina Ward oversees the cancer clinical trials Lee Health. “Research is done for just about anything. There are studies for all kinds of different diagnosis, different studies. There are studies that are not even treatment-related. There are some studies that are just looking at the quality of life.” Find clinical trials near you HERE.
Immunotherapy vs. Breast Cancer. In a landmark study, a patient’s advanced breast cancer regressed completely after treatment with immune cells that recognized products of mutations specific to her cancer.
In an ongoing NCI-led clinical trial at the NIH Clinical Center, a patient with metastatic breast cancer has experienced complete regression of her disease after treatment with an experimental immunotherapy developed in CCR. Despite multiple prior cancer treatments, her cancer continued to enlarge and spread until she received this new treatment. The case report, published in Nature Medicine, highlights the potential of immunotherapy for difficult-to-treat solid tumors.
Although cancer immunotherapies have brought about complete regression of disease in some patients, certain types of cancer, including breast cancer, have been difficult to treat with these approaches. The experimental approach being tested in the current trial, developed by CCR Surgery Branch Chief Steven A. Rosenberg, M.D., Ph.D., and colleagues, uses immune cells selected for their ability to recognize cells with mutations specific to a patient’s tumor to fight their disease—a strategy that Rosenberg says may serve as a blueprint to treat many cancers.
This type of immunotherapy, called adoptive cell transfer (ACT), uses cancer-fighting cells from a patient’s own immune system that are grown in large numbers in the laboratory and then infused into the patient. The specific form of ACT being investigated uses immune cells that have been isolated directly from a patient’s tumor, known as tumor-infiltrating lymphocytes (TILs). The key to this approach is the identification and use of only TILs that specifically recognize proteins encoded by genetic mutations present in the patient’s cancer.
The TILs used to successfully treat this patient’s breast cancer were selected after researchers compared the DNA and RNA from one of her tumors to her normal tissue and identified 62 mutations unique to her cancer. Next, the TILs isolated from her tumor were tested for their ability to recognize the products of these mutations. TILs recognizing proteins encoded by four different cancer-specific mutations were then selected for treatment. Along with the tumor-specific immune cells, the patient was given pembrolizumab, an immune system checkpoint inhibitor that allows cancer-fighting cells to remain active in the microenvironment of a tumor, and interleukin-2, which promotes immune cell growth.
More than three years after the treatment, the patient’s breast cancer has not returned. The team has also seen this type of immunotherapy trigger tumor regression in patients with liver cancer, colorectal cancer and cervical cancer, offering hope that it might be a broadly effective treatment strategy.
October 1, 2019
PINEHURST – The American Cancer Society estimates that by the year’s end in the United States 268,600 new cases of invasive breast cancer will be diagnosed in women and 41,760 will die from the disease. In North Carolina, where breast cancer ranks at the top of all new cancer diagnoses, that breaks down to 8,870 new cases and 1,390 deaths.
“There is a one in eight chance that a woman will be diagnosed with invasive breast cancer during her lifetime,” said Sushma Patel, M.D., a radiation oncologist with FirstHealth of the Carolinas. “While rates of death due to breast cancer are declining due to better screening and improved treatment options, we still have a long way to go.”
To aid in the battle against breast cancer, FirstHealth of the Carolinas joins National Breast Cancer Awareness Month, a campaign held every October to increase awareness of the disease and the importance of early detection.
“Early detection of breast cancer, when it’s small and contained, is the key to improved survival,” said Patel. “It’s essential that women have an annual mammogram, conduct a (monthly) self-exam and watch for changes in their breasts, including swelling, skin thickening or redness, breast warmth or itching and nipple discharge.”
ACS recommends women with an average risk of breast cancer to have yearly mammograms by age 45, but women at a high risk for the disease should talk with their physicians about starting mammograms earlier. Contributing factors to a higher risk include a family history of the disease; a known BRCA1 or BRCA2 gene mutation in the patient or in a first-degree relative (parent, brother, sister or child); radiation therapy to the chest between the ages of 10 and 30 years; or have Li-Fraumeni syndrome, Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, or first-degree relatives with one of these syndromes.
As men have breast tissue, they are also at risk for the disease, although at a much lesser rate; their lifetime risk is 1 in 833. The ACS estimates that by the end of 2019 about 2,670 new cases of invasive breast cancer will be diagnosed in American men and 500 will die from the disease.
Fortunately for patients in the Sandhills, the FirstHealth Cancer Care team offers comprehensive breast cancer care including screening and diagnostic imaging, breast biopsies, breast cancer surgery, medical and radiation oncology, genetic testing and clinical trials. For patients with any cancer diagnosis, a deep and wide array of support services is at the ready, including oncology nurse navigators who support and guide patients through their cancer journey, a financial navigator, nutritionists, social workers, support groups and spiritual counseling, cancer wellness programs, CareNet volunteers and many other supports that patients are referred to as necessary.
“Patients need to focus on getting well, not worry about barriers to care,” said Lynn Lanier, MSN, R.N., ONN-CG, an oncology nurse navigator at the FirstHealth Outpatient Cancer Center. “These supports are carefully designed to help lessen the anxiety associated with a cancer diagnosis and treatment.”
Sandhills residents can join FirstHealth in the fight against breast cancer in a number of ways:
— Participate in the 1in8k Run for Moore, a 1k fun run and 8k run/walk on Saturday, October 12. This annual community event in the Village of Pinehurst raises funds to fight breast cancer, increases public awareness and allows individuals to honor and support those who have battled or are currently battling the disease. Information is available at www.firsthealth.org/1in8k.
— Get a mammogram at any FirstHealth facility in October and receive a free pink lunch bag. Find locations at www.firsthealth.org/imaging and call (866) 415-2778 to schedule.
“I am looking forward to the day when the ‘1 in 8’ statistic changes to ‘1 in a million’,” said Patel. “We just need to keep working to achieve that goal.”
FirstHealth of the Carolinas is a SCOR member site located in the Pinehurst, NC area.
Clinical trials typically are conducted through a sequence of phases, each successive stage building upon the last. Each of these phases is designed to address a specific set of questions and having knowledge of each phase is essential in understanding what is currently known about an experimental therapy. There are benefits and drawbacks associated with moving a treatment into each specific phase.
The clinical trial is only conducted when researchers have reason to believe that a new treatment or test could significantly improve patient care. Before these trials are carried out, the treatment or test is first evaluated in preclinical research.
Preclinical Trials: Before Testing in Humans
Preclinical trials assess the features of the proposed solution through cellular research and experiments with tissue and animal models. The goal of the preclinical trials is to ensure that the solution is safe to use before testing it in humans during clinical trials.
After this preclinical research, a series of clinical trials are then conducted. These trials assess whether the test or treatment is safe and effective in human patients. These clinical trials are conducted in five phases, which will be explained below using the example of an experimental drug.
Phase 0: Small Doses in Humans
Phase 0 trials mark the first clinical trials done in humans. The goal of this phase is to learn a drug is processed by the body and what effects it can have. These trials recruit about 10-15 people who are given a minuscule dose of the drug. The purpose of this phase is to facilitate the drug approval process. Researchers can assess several factors in this stage, like whether the drug reaches the target site, how cells respond to the drug, and how the patient tolerates the dose.
What sets phase 0 trials apart from the latter phases is that it is very unlikely that the participant will see any benefit. These low dosages administered during this phase allow the researchers to evaluate the drug’s effectiveness while minimizing risk in the patients. This step allows scientists to recognize flaws in essential steps like drug absorption early, rather than having to address this years down the road in later phase trials.
Phase 0 studies are not always used, being that they would not be helpful for some drugs. This stage is not required for the testing of a new treatment.
Phase I: Evaluating Safety
Trials in phase I aim to identify which doses of a drug yield the least side effects. The drug is tested in groups of 15-30 patients in this stage, with doctors giving them the drug in various doses. The first few patients are given a very low dose and if they show negligible side effects, the next participants receive a higher dosage. This is repeated until the researchers find the quantity of the drug that is likely to be effective while producing an acceptable amount of side effects.
These trials do not use placebos and are typically considered to have the most potential risk. Though patients may see some benefits from the drug in phase I, the primary goal of this stage is to test the drug’s safety in humans. If the drug is found to be safe, it is then tested in a phase II clinical trial.
Phase II: Testing the Drug’s Effectiveness
Phase II trials aim to further validate the treatment’s safety, often narrowing the participant cohort to those with a specific condition. Phase II trials recruit more participants than phase I trials, with about 25-100 participants typically involved. These patients are given the optimal dose identified in the phase I trial and are closely observed to see if the proposed treatment is effective. Participants in phase II trials typically all receive the same dose, but some studies randomly assign participants to receive different doses or routes of administration. No placebos are used in phase II clinical trials.
Phase III: Comparing to Current Treatments
The phase III trials aim to compare a new drug to the standard-of-care drug, or the current drug used to treat a condition. These experiments compare the side effects and efficacies of each drug to determine which is best for the patient. Phase III trials typically involve several hundred patients.
These trials are often randomized, meaning that the participants are randomly assigned to receive either the experimental drug or the standard-of-care drug. This randomization is important in ensuring that the participants are alike in each group, therefore any differences in outcomes can be attributed to the treatments, not the group composition.
Phase III trials are typically conducted in various locations throughout a country or even internationally. These studies are also longer than phase I and II trials in duration. Placebos can be used in phase III trials, but they are never used alone if there is also a standard-of-care treatment available for the patients. These trials are terminated if the side effects of the experimental drug are becoming too severe or if one group is performing significantly better than the other. The phase III clinical trial is often required for the FDA to approve the use of a new drug.
New Drug Application (NDA)
When an experimental drug outperforms the standard-of-care in a phase III trial, an NDA is submitted to the FDA for approval in the U.S. The FDA reviews the results from the trials and decides whether the drug is worthy of approval for use in patients. If approved, this new treatment often becomes the new standard-of-care. The FDA can also deem that further research is needed to show that the drug’s benefits outweigh its risks and request that more studies be conducted.
Phase IV: Large-Scale Studies After Approval
These trials aim to test new drugs that the FDA has approved. The drug is evaluated in hundreds or thousands of patients, allowing for more information regarding short-term and long-term side effects to be obtained. These trials may uncover rare side effects that are only seen in large groups of people. Physicians are also able to learn from phase IV trials by seeing how a drug works in concert with other medications. These trials can look at other aspects of the drug as well, such as cost-effectiveness and its effect on quality of life.
Twin sisters Marlene Thomas and Darlene Reeves of Pinehurst have always shared. Not only do they share the same physical features and the same dental hygienist job (one works three days a week and the other two, then they switch), but they also experienced similar types of cancer.
In May 2013, Reeves was diagnosed with stage 3C primary peritoneal carcinoma, a type of cancer that can originate from the same type of cell that lines the surface of the ovaries and fallopian tubes. She was successfully treated and is now back in the dental hygienist chair.
Since they share the same DNA, Thomas decided to get checked out and underwent a hysterectomy in April 2014. Given her sister’s history, Thomas’ gynecologic oncologist, Dr. Michael Sundborg of FirstHealth Outpatient Cancer Center, analyzed the removed ovary and uterus and found stage 3A low-grade serous ovarian cancer. This is less common and aggressive than high-grade types of ovarian cancer but is resistant to many kinds of chemotherapy and carries a high likelihood of relapse after treatment.
Thomas’ five months of chemotherapy ended in September 2014, and Dr. Sundborg determined her clear of cancer. He told her that her history would make her a good candidate for a new “cancer control” clinical trial sponsored by Gynecologic Oncology Group. The study’s goal was to determine if diet and exercise can help control cancer recurrence in patients who were successfully treated for low-grade serous ovarian cancer. The study hosted two groups — patients in a test group were assigned a life coach who helped patients adopt a healthful diet and exercise regimen and patients in the control group were counseled to continue their normal daily habits and were given a pedometer to track activity. Thomas agreed to participate and was randomly assigned to the latter control group, though she admits she would have preferred to be in the test group with the life coach.
Every six months of the two-year trial, Thomas completed a questionnaire and occasionally had blood drawn at FirstHealth Outpatient Cancer Center that was analyzed by the study’s researchers. Her active participation in the study ended in 2017, but researchers from the Gynecologic Oncology Group call her annually to ask her what’s new with her health, how she is feeling and other general questions. Her consistent response? “I feel alright!” Like Reeves, Thomas is back in their shared dental hygienist’s chair and is enjoying life.
Results from Thomas’ participation in the clinical trial are being analyzed with those of more than 1,000 other participants and overall results are not yet available. While she did not benefit directly from this experience, her participation will help patients in years to come, and she reports that is benefit enough for her.
Now an avid supporter of early cancer detection, Thomas counsels nearly all women she encounters that pap tests don’t necessarily detect all types cancer specific to women. Her advocacy has also earned her a spot on FirstHealth Cancer Services’ Cancer Advocacy Advisory Board for which she volunteers to educate fellow patients about clinical trials from a peer perspective.
Patients and their families seeking more information about clinical trials at FirstHealth of the Carolinas can visit https://www.firsthealth.org/reference/clinical-trials or talk with the patient’s physician.