Clinical Trials

Study : NANT 2004-04

Oral Fenretinide LXS Powder in Recurrent or Resistant Neuroblastoma Patients

Protocol Title: A Phase I Study of Fenretinide Lym-X-Sorb^TM (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.

To determine if the levels of fenretinide in the blood is higher with the new way of giving fenretinide. In the early part of the study, 3% fenretinide was mixed with SlimFast and given twice daily. Some children found it difficult to take the medicine and some did not like the taste of SlimFast. In this latter part of the study, 2.2% fenretinide will be prepared in a special mixture of fats, sugar and wheat flour (called Lym-X-Sorb^TM (LXS) oral powder) and will be given with any type of food that does not have high amounts of milk fat three times per day.
(Cohort 2 Only) To find a dose of a drug used for fungal infections, called ketoconazole, that can be given by mouth (orally) once each day, for 7 days, every 3 weeks, in combination with fenretinide without causing severe side effects.
To find out the side effects seen by giving 2.2% 4-HPR/LXS oral powder with (Cohort 2) or without ketoconazole (Cohort 1).
To measure blood levels of fenretinide during treatment with or without ketoconazole.
To measure levels of fenretinide in normal white blood cells during treatment.
To determine if your tumor gets smaller after treatment with 4-HPR/LXS oral powder with or without ketoconozole.

Criteria that need to be met to participate in this study:

Patients must be no more than 30 years of age when registered on this study.
Patients must have relapsed neuroblastoma, refractory neuroblastoma that had less than a partial response to standard treatment or persistent neuroblastoma that had at least a partial response to standard treatment.
Patients who have at least a partial response to standard treatment who still have neuroblastoma that can be seen on CT/MRI or MIBG scans must have a surgical biopsy done of the tumor to confirm that it is neuroblastoma. Patients with relapsed or refractory neuroblastoma do not need to have a biopsy done to enter on study.
Patients who will only be getting the Fenretinide (without ketoconazole) can participate if they have had a prior relapse or progression, even if they have no measurable or evaluable tumor sites at time of study entry
Patients must have adequate heart, kidney, liver and bone marrow function. Patients who have bone marrow disease must meet the bone marrow function criteria to enter the study.
Patients must consent to participate in pharmacokinetic studies (measure the level of fenretinide in the blood).

Patients cannot participate in the study if:

They have been treated before with Intravenous Fenretinide. They can enter on study if they had treatment before with 3% 4-HPR/LXS oral powder, with the fenretinide corn oil capsule or other retinoids such as 13-cis-Retinoic Acid.
Neuroblastoma is present in the brain on a CT or MRI scan done at study entry. Patients with neuroblastoma found in the bones of the skull are eligible if there is no tumor mass associated with them pressing on the brain.
They are pregnant or breast feeding.
They have an allergy to soy products or allergy or sensitivity to wheat gluten.
They need medications to maintain a stable heart rhythm.
They have had an organ transplant (like kidney or liver) or an allogeneic stem cell transplant in the past (Using stem cells from a donor other than yourself).

Study procedures:

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.

Cohort 1:

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.

Cohort 2:

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.

The Childrens 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 (323-361-8368).

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