Clinical Trials

Study : NANT 2004-03

A Phase I study of intravenous fenretinide in pediatric neuroblastoma

Protocol Title: A Phase I Study of Intravenous (Emulsion) Fenretinide (4-HPR, NSC 374551) in Children with Recurrent or Resistant Neuroblastoma (IND #70,058)

Study Chair: Barry Maurer MD, PhD. (Texas Tech University Health Sciences)

What is this study about

Fenretinide is an anticancer agent that may work differently than standard chemotherapy medicines. It may cause the build up of a wax-like substance in neuroblastoma cancer cells, called "ceramide". In laboratory studies it was found that if too much ceramide builds up in neuroblastoma cells, they die.

Fenretinide has been given by mouth as a capsule to many people, including children. When Fenretinide is given in capsules, very little of the drug is absorbed through the intestines into the body. That meant that patients had to take many capsules of Fenretinide by mouth several times a day. In this study, an intravenous preparation of fenretinide (called an "emulsion") is being tested to see if more fenretinide can be delivered into the body by giving it into the veins rather than by mouth using capsules. This is the first study of intravenous emulsion fenretinide in children.

Why is this study being done

The purposes of this study are:

To find the highest dose of emulsion fenretinide that can be given intravenously for 5 days, every three weeks, without causing severe side effects.
To find out the side effects seen by giving intravenous emulsion fenretinide on this schedule at different dose levels.
To measure blood levels of fenretinide during treatment.
To measure levels of fenretinide in normal white blood cells during treatment.
To determine if your tumor gets smaller after treatment with intravenous emulsion fenretinide

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 must have adequate heart, kidney, liver, pancreatic 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 Fenretinide and the drug was stopped or the dose was reduced because of side effects.
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 bean oil or egg products.
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

The initial part of this study tested several doses of intravenous fenretinide, with higher doses in each group of patients. That part of the study has been completed. One of two patients treated at the highest dose level tested died of liver failure, which was thought to be related to a drug-drug interaction of the fenretinide with other medicines. The study has now been amended to lower the dose of fenretinide below the highest dose tested.

Six patients have already gotten the next lower dose level and had no significant side effects. We plan to treat more patients at lower doses, to obtain further safety data and measure the levels of fenretinide in the blood.

Patients will not be allowed to receive a certain antibiotic (ceftriaxone) or acetaminophen (Tylenol) while they are getting the IV fenretinide. 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.

The dose of fenretinide will not be increased with later courses of treatment.

Your dose of IV fenretinide could be decreased if you have significant side effects.

Financial Disclosure

Childrens Hospital Los Angeles (CHLA) holds patents and/or patent applications on anti-cancer therapies using Fenretinide (the study drug). This drug has been licensed to the company CerRx, Inc. founded by the two inventors, Drs. Barry Maurer, and C. Patrick Reynolds (Texas Tech University Health Sciences Center, Lubbock, Texas). CHLA may benefit financially from the 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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