Study : NANT 2004-04
Oral Fenretinide LXS Powder in Recurrent or Resistant Neuroblastoma Patients
Protocol Title: A Phase I Study of Fenretinide Lym-X-SorbTM (LXS) Oral Powder in Patients with Recurrent or Resistant Neuroblastoma (IND # 68,254)
Study Chair: Barry Maurer MD, PhD. (Texas Tech University Health Sciences Center)
What is this study about:
Fenretinide is an agent that works differently from standard chemotherapy drugs in treating cancer. Fenretinide may cause the build up of a wax-like substance in neuroblastoma cancer cells, called "ceramide". In laboratory studies, it has been found that if too much ceramide builds up in neuroblastoma cells, they die.
In the past, Fenretinide has been given to people (including children) with cancer. It has only been able to be given as a large capsule - this meant it was difficult for many children (especially ones who are small) to swallow the number of pills they needed to. When Fenretinide is given in capsules, very little of the drug is absorbed through the intestines into the body. In this study, an investigational oral preparation of fenretinide (called 4-HPR/LXS powder) is being tested to see if more fenretinide can be absorbed into the body than was seen with the large capsules. This is the first study of 4-HPR/LXS powder in either children or adults. This investigational oral preparation of fenretinide has not been approved by the Food and Drug Administration (FDA). This clinical research study will help find out the highest dose of oral fenretinide LXS powder that can be safely given to patients with resistant or recurrent neuroblastoma.
Why is this study being done:
This study will be divided into two cohorts of patients, which are explained below. Cohort #1 will be completed before Cohort #2 begins.
Criteria that need to be met to participate in this study:
Patients cannot participate in the study if:
This study will be divided into two cohorts of patients. Each cohort will include 12 patients. Cohort #1 will be completed before Cohort #2 begins.
In twelve patients enrolled in Cohort 1, 4-HPR/LXS oral powder mixed in foods or liquids that do not have a large amount of milk fat will be given by mouth three times a day, for 7 days, every three weeks. The powder mixed can be taken with any room temperature or colder food or liquid/beverage EXCEPT food or liquids that are high in milk fat. The drug powder can also be mixed in fruits or flavorings as long as they don't have large amounts of milk fats in them. This means ice cream or whole or 2% milk cannot be used. Milk fats may change the drug so it may not be the same. Patients do not need to be in the hospital to receive the drug. If there are bad side effects, patients may continue treatment with a lower dose of 4-HPR/LXS oral powder, provided side effects have gone away and the tumor is not getting worse.
All patients will get the same dose of 4-HPR/LXS oral powder that has already been shown to be tolerated without bad side effects in several children with neuroblastoma. The dose will not change with later courses of treatment, unless it needs to be decreased due to side effects.
In twelve patients enrolled in Cohort 2, the same dose of fenretinide will be given, but patients will also take a common antifungal drug called ketoconazole, along with the 4-HPR/LXS oral powder. We are testing to see if ketoconazole can further increase fenretinide levels in the body by slowing down the body's ability to get rid of fenretinide If the dose of ketoconazole causes side effects, then a third group of patients will be treated at a lower dose of ketoconazole with the same dose of fenretinide as all other patients.
Patients will not be allowed to receive a certain antibiotic (ceftriaxone) or acetaminophen (Tylenol) while they are getting the 4-HPR/LXS oral powder and ketaconazole in Cohort #2. This is due to a death from liver failure on one of the patients treated at the highest dose level of IV fenretinide, which was thought to be related to a drug-drug interaction of the fenretinide with other medicines.
If needed, patients will be given other, equally effective antibiotics needed to treat a suspected infection during the time when ceftriaxone is prohibited. All patients and families enrolled will be given specific instructions as to when these medications must be avoided when on therapy.
Children's Hospital Los Angeles (CHLA) holds patents and/or patent applications on Fenretinide Lym-X-Sorb oral powder (the study drug). The inventors of Fenretinide Lym-X-Sorb oral powder, Drs. Barry Maurer and C. Patrick Reynolds (Texas Tech University Health Sciences Center, Lubbock, TX) and CHLA may potentially benefit financially from the development and future use of the study drug. If you have any questions regarding this disclosure, please contact the Conflict of Interest in Research Committee (COIRC) at CHLA (323-361-4832).