Epigenetic Therapy for Patients with Surgically Resected Early Stage Lung Cancer
Traditionally, patients with early stage lung cancer have been monitored with CT screenings to see if the cancer returns, there have been no additional treatment options for surgery. Now, at Johns Hopkins, there is a new therapy that is being investigated for patients after surgery. This new treatment utilizes epigenetic therapy in the treatment of early stage lung cancer.
The experimental use of epigenetic therapy after surgery is being compared to the current standard of care which is supportive care after surgery for patients diagnosed with Stage 1 Non-Small Cell Lung Cancer (NSCLC).
What is Epigenetic Therapy and How is it Different?
Epigenetic therapy represents a novel concept in treating cancer. It has not been FDA-approved for the use in lung cancer. The doses of the drugs given are lower than the maximally tolerated doses of these drugs, which may limit the toxicity.
The goal of this type of therapy is not to kill the cancer cells directly. Instead, the objective is to allow the cells to live to absorb the drugs. The drugs then change the cancer cells from the inside out, making them a more normal cell. Since the Epigenetic Therapy is given in a low does, it has fewer side effects than standard chemotherapy.
Who Can Join?
Eligible participants may include those with:
- Patients that have received complete resection of pathologically proven NSCLC (stage 1A or 1B).
- Must be between 4-8 weeks out from surgery.
- Must be older than 18 years of age.
- Must not have received any chemotherapy or radiation therapy for your lung cancer.
- Must have acceptable lab values and assessed to be in a good state of health.
What is Involved?
- Eligble patients will be randomized to epigenetic treatment consisting of two drugs; 5-Azacitidine & Entinostat or standard of care
- All patients will need to spit into a cup, have blood samples drawn, and receive physical examinations as well as radiological imaging.
- Patients that are randomized to epigenetic treatment will receive subcutaneous injections in the outpatient setting on days 1-5 and 8-10, and an oral agent on days 3&10 of each 28-day cycle. Up to 6 cycles of treatment will be given.
- Patients randomized to standard of care will be followed with CT screenings and collections of research labs every 3 months for the first 2 years and then every 6 months after that.
For More Information
If you think this trial may be right for you, contact us. We will help determine if you may be eligible for the trial and answer any questions.
Joanne Riemer, RN
443-287-4114 - firstname.lastname@example.org
Malcolm Brock, M.D.
410-955-8506 - email@example.com
Charles Rudin, M.D.
410-502-0678 - firstname.lastname@example.org
Beverly Lee/Kristen Rodgers
This study is funded by Stand Up 2 Cancer
For more information or to see if you qualify, call 410-955-8804 or email HopkinsBreastTrials@jhmi.edu.
A new clinical trial for breast cancer patients will test the effects of two drugs, called 5-Azacitidine (5-AZA) and Entinostat. Preliminary results from clinical trials at Johns Hopkins in cancers other than breast cancer indicate that this combination is safe and tolerable and associated with improved outcome for certain patients. The drugs are believed to work by targeting specific changes that occur in important breast cancer genes.
Who can Join?
Eligible participants may include those with:
- a diagnosis of triple negative breast cancer
- hormone-resistant (HER2-negative) breast cancer
- advanced breast cancer, or inoperable breast cancer
- metastatic breast cancer
In addition, patients must have measurable disease that can be biopsied prior to and during the trial, and be in good health. 5-Azacitidine is given by injections and an Entinostat pill is taken orally at Johns Hopkins or a participating site eight days each month over a 10-day period. Patients with progressive disease may continue the drugs in combination with hormonal therapy, such as tamoxifen or letrozole, at the discretion of the treating physician.
To find out if you may be eligible, call the Clinical Trials Line at the Johns Hopkins Kimmel Cancer Center at 410-955-8804 or email HopkinsBreastTrials@jhmi.edu. To locate a center near you, visit clinicaltrials.gov trial identifier: NCT01349959
Johns Hopkins IRB-Approved Study #NA_00046053
Brachytherapy is a type of radiation treatment that is given internally in the rectum, directly to the tumor. Herman and surgeon Susan Gearhart are currently conducting the first U.S. study to look at its effectiveness in low rectal cancers, those less than 12 centimeters from the rectum.
Treatment for rectal cancer includes a surgical procedure called a total mesorectum excision to remove lymph nodes and blood vessels in the tissue adjacent to the rectum that could contain cancer cells and lead to a cancer recurrence. With surgery alone, about 10 to 15 percent of patients will have their cancers come back, usually within just a few centimeters of the original tumor, so patients typically receive chemotherapy and radiation therapy to the pelvis in an attempt to stave off the cancer’s return.
However, with such low recurrence rates,Herman wonders if doctors may be overtreating the cancer, and whather a type of brachytherapy might achieve the same or better results. The technique is called endorectal brachytherapy, and it uses a cylinder-shaped applicator probe inserted into the patient’s rectum. After the probe is placed in the rectum, a wire with a radiation source at the tip is slowly inserted into the applicator. As it moves through the applicator, it delivers very focused radiation to the surface of the tumor. This highly focused radiation targets the tumor, and lesser amounts reach the nearby tissue surrounding the tumor that could contain cancer cells. Normal tissue, including the bladder, small intestine, and reproductive organs, are farther away from the probe and almost completely spared from radiation. The treatment takes only 15 minutes and the radiation is completely removed from the body afterwards.
In this new study, patients received four days of endorectal brachytherapy before having surgery (without concurrent chemotherapy), as opposed to 28 days of external (X-ray) beam radiation therapy in standard treatment. Among the benefits, Herman says, is that endocrectal brachytherapy is significantly less expensive and likely decreases the risk of bowel complications and secondary cancers. It also delivers less radiation to the bladder and reproductive organs. Moreover, Herman says the shortened duration of treatment gets patients to surgery five to six weeks sooner and, for the most part, with fewer complications afterwards.
“In about half of patients, the tumor spreads after surgery. With fewer problems after surgery,we can get them to chemotherapy more quickly and, hopefully, stop some of these cancers from spreading,” he says. With standard therapy, treatment is longer and some patients have a further lag time as they wait for tissue damaged during treatment to heal.
The standard therapy also treats lymph nodes in the pelvis, and, Herman says, with recurrences rates under five percent in the pelvic region,likely unnecessary.
When compared to standard X-ray or external beam radiation,Herman says endorectal brachytherapy may be more effective and less toxic. “With endorectal brachytherapy, 30 percent of patients have a complete response—their tumors are eradicated and there are fewer effects to normal tissue. In external beam radiation, only 10 to 15 percent of patients have a complete response, and there is more toxicity to normal tissue,” he says.
Although early studies are promising, Herman says he needs to evaluate the treatment in more patients. In addition, he cautions that endorectal brachytherapy is not for all rectal cancer patients. Of the approximate 80,000 new cases of rectal cancer diagnosed each year,Herman estimates that about half of these people would be good candidates for endocrectal brachytherapy. Ideal candidates have tumors that the endorectal probe can reach and pass by and have not spread to pelvic lymph nodes or other tissue and organs beyond the rectum. “Even if we find endrorectal brachytherapy only works as well as standard therapy, there is still a benefit,” says Herman. “It reduces toxicities, gets patients to surgery sooner, and costs less.”
For more information on the endorectal brachytherapy trial, contact Beth Griffith at 410-502-9243.
Dr. Herman can be contacted at 410-502-3823.