Phase I Study of Fenretinide (4-HPR, NSC 374551) Lym-X-Sorb (LXS) Oral Powder Plus Ketoconazole Plus Vincristine in Patients With Recurrent or Resistant Neuroblastoma (IND #68,254) (SPOC2013-001)

NCT02163356 Phase 1 TERMINATED

Currently there is no known effective treatment for recurrent or resistant neuroblastoma. Fenretinide is an anticancer agent that may work differently than standard chemotherapy. It may cause the buildup of wax-like substances in cancer cells called ceramides. In laboratory studies, it was found that if too much ceramide builds up in the 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. This means patients have to take many capsules of fenretinide by mouth several times a day. In this study, a new oral preparation of fenretinide (called 4-HPR/LXS oral powder) is being tested to see if more fenretinide can be absorbed into the body. 4-HPR/LXS oral powder has been tested previously in a limited number of both children and adult cancer patients. Ketoconazole, commonly used to treat fungus infections, can increase fenretinide levels in the body by interfering with the body's ability to break down fenretinide. Ketoconazole will be given at the same time as the fenretinide powder. There is preclinical data that shows that combining fenretinide and vincristine prolonged survival in animal models, therefore, it is hoped that giving the vincristine with fenretinide will work better against the neuroblastoma that either drug given alone. About 70 children with neuroblastoma have been treated with various versions of the fenretinide powder to date, including about a dozen children that also took the fenretinide powder with ketoconazole, and no toxicities have occurred that limited the dosage and no serious or unexpected side effects occurred. However, vincristine has never been given with fenretinide or fenretinide plus ketoconazole before. Vincristine has been been given before with ketoconazole to both children and adults with neuroblastomas and other cancers.

Details

Lead sponsor	South Plains Oncology Consortium
Phase	Phase 1
Status	TERMINATED
Enrolment	4
Start date	2014-05
Completion	2018-05

Conditions

• Recurrent Neuroblastoma
• Neuroblastoma

Interventions

• Fenretinide/LXS Oral Powder
• Ketoconazole
• Vincristine

Primary outcomes

• Maximum Tolerated Dose — after each subject has completed 1 cycle of therapy (a cycle is 21 days)
  To determine maximum dose of vincristine when given in combination with 4-HPR/LXS and ketoconazole. Subjects will be enrolled in a standard 3 + 3 design and will receive set doses of HPR/LXS and ketoconazole. Vincristine will be escalated with each dose level up to 1.5 mg/m2. If toxicity occurs due to vincristine, the dose level will be expanded or dose decreased to the previous level as appropriate. If toxicity occurs due to ketoconazole, the dose level will be expanded and the ketoconazole dose decreased to 3 mg/kg/day
• Side effect profile of drug combination — after each subject receives the drug combination (a cycle is expected to be 21 days)
  The side effect profile of the combination therapy will be compared to known single agent side effects looking for new unique drug interactions.
• Assess plasma pharmacokinetics of fenretinide — On day 1 (hour 0, 2, 4, 6), day 7 (hour 0, 2, 4, 6) and day 9 (after 3 pm) for course 1. For courses 2 and 6, day 1 (hour 0, 4 and 6), and day 7 (hour 0, 4, and 6)
  included analysis of metabolites (4-MPR and 4-oxo-HPR) and related plasma sphingolipids

Countries

United States