Protocol Number: 08-C-0030

Title:

Phase I Trial of Fenretinide (4-HPR, NSC 374551) Lym-X-Sorb (LXS) Oral Powder (4-HPR/LXS Oral Powder) (4-HPR) in Adults With Solid Tumors and Lymphomas

Number:

08-C-0030

Summary:

Background:

-An experimental drug known as fenretinide has been shown in the laboratory to have activity against tumors. It has been given by mouth in capsule form to adult and child cancer patients, but because the drug is not easily absorbed in capsule form, patients must take many fenretinide capsules daily to see any effect.

-A new oral preparation of fenretinide in powder form (fenretinide/LXS oral powder) may be more easily absorbed by the body, but further tests are needed to determine the safety and effectiveness of this new form.

Objectives:

-To test the safety of fenretinide/LXS oral powder in adults.

-To determine the maximum tolerated dose of fenretinide/LXS oral powder (the highest dose that does not cause unacceptable side effects).

-To see if fenretinide/LXS oral powder has any effect on patients' tumors.

-To learn how the body handles and processes fenretinide/LXS oral powder.

Eligibility:

-Individuals 18 years of age or older who have a solid malignant tumor that has not responded to standard treatments.

-Individuals who have brain tumors or other clinically significant illnesses, or who are allergic to wheat gluten, are not eligible for the study.

Design:

-Treatment with fenretinide/LXS oral powder for a maximum of six 21-day cycles as follows:

---Week 1 - Fenretinide/LXS oral powder mixed in a liquid nutrition supplement, applesauce, or apple juice (approximately ? to 1? cups per dose), taken twice a day.

---Weeks 2 and 3 - No fenretinide/LXS oral powder.

-NOTE: Because retinoid drugs like fenretinide are known to cause birth defects, the Clinical Center will provide special gloves, masks, and mixing cups to ensure that others are not exposed to the study drug by accident.

-Evaluations during the treatment period:

---Physical examinations, including vital signs and body weight checks, and pregnancy test for women who can become pregnant.

---Questions about side effects.

---Blood and urine tests.

---Inpatient visits during the first and second cycle, and clinic visits at the beginning of every cycles . Lab test required weekly, can be done by local physician

---Other special tests:

---Blood samples for pharmacokinetic studies (to measure the amount of fenretinide in the blood).

---Blood samples for pharmacodynamic studies (to measure the amount of fenretinide in white blood cells).

-Post-treatment evaluations:

---End-of-study visit for blood tests, vital signs and weight measurements, disease assessment, echocardiogram, electrocardiogram, and pregnancy test for women who can become pregnant.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

Patients must have histologically confirmed (by the NIH pathology department) solid tumor malignancy that is metastatic or unresectable or lymphoma for which the standard treatment or curative measures do not exist, or are associated with minimal patient survival benefit.

Patients must have measurable or evaluable disease.

Patients must have recovered to at least a Grade less than or equal to 1 toxicity levels due to adverse events and/or toxicity of prior chemotherapy or biologic therapy. They must not have had chemotherapy or biologic therapy within 4 weeks prior to entering the study (6 weeks for nitrosoureas or mitomycin C, or UCN-01). Patients can be greater than or equal to 2 weeks since any prior administration of study drug in an exploratory IND/Phase 0 study. Patients must be greater than or equal to 1 month since any prior radiation or major surgery. However, patients receiving bisphosphonates for any cancer or undergoing androgen deprivation therapy for prostate cancer are eligible for this therapy.

Age greater than or equal to 18 years.

The Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 (Karnofsky greater than or equal to 60 percent).

Life expectancy greater than or equal to 3 months.

Patients must have normal or adequate organ and marrow function as defined below:

-Absolute neutrphil count greater than or equal to 1,500 microliters

-Platelets greater than or equal to 100,000 microloters

-Total bilirubin--- within less than or equal to 1.5 normal institutional limits

-AST (SGOT)/ALT (SGPT) less than or equal to 2.5 times institutional upper limit or normal

-Creatinine less than 1.5 times upper limit of normal

OR

-Measured creatinine clearance greater than or equal to 60mL/min/1.73 m (2) for patients with creatinine levels greater than or equal to 1.5 times upper limit of normal

We will allow patients with CTCAE v. 3 Grade 1 thrombocytopenia if explained by involvement of the bone marrow by lymphoma

We will allow patients with Gilbert's syndrome with total bilirubin up to 2.5 mg/dL

The effects of fenretinide on the developing human fetus are unknown. Fenretinide is a retinoid, and retinoids are known to cause birth defects. For this reason, women of child-bearing potential and men must either abstain from sexual intercourse or use two methods of birth control. This must include at least one highly effective method such as the intrauterine device (IUD), hormonal birth control pills/injections/implants, tubal ligation or partner's vasectomy, and one additional effective method such as latex condoms, diaphragm, or cervical cap, prior to, during, and for 2 months after, completion of fenretinide/LXS oral powder treatment. Men must use a latex condom every time they have sexual intercourse during therapy and for 2 months after discontinuing fenretinide, even if they have had a successful vasectomy. Women of child bearing potential must have a negative pregnancy test in order to be eligible. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with fenretinide, breastfeeding should be discontinued if the mother is treated with fenretinide.

Ability to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA

Patients receiving any other investigational agents.

Patients with known brain metastases are excluded from this clinical trial, with the exception of patients whose brain metastatic disease status has remained stable for greater than or equal to 3 months after treatment of the brain metastases, (without steroids or anti-seizure medications). These patients may be enrolled at the discretion of the principle investigator.

Patients with clinically significant illnesses which could compromise participation in the study, including, but not limited to, active or uncontrolled infection, immune deficiencies or confirmed diagnosis of HIV infection, uncontrolled diabetes, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Patients with known wheat gluten allergy or allergy or sensitivity to the study drug.

Patients taking sulfonamides.

Patients with a history of pancreatitis defined as elevated amylase or lipase greater than or equal to Grade 2 and accompanied by symptoms of pancreatitis (e.g., abdominal pain).

Special Instructions:

Currently Not Provided

Keywords:

Fenretinide

Solid Tumors

Lymphomas

Phase I

Pharmacokinetics

Recruitment Keyword(s):

Solid Tumor

Lymphoma

Condition(s):

Neoplasms

Lymphomas

Investigational Drug(s):

Fenretinide

Investigational Device(s):

None

Intervention(s):

Drug: Fenretinide

Supporting Site:

National Cancer Institute

Contact(s):

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
Phone: 1-888-NCI-1937
Fax: Not Listed
Electronic Address: ncicssc@mail.nih.gov

Citation(s):

Ziv Y, Gupta MK, Milsom JW, Vladisavljevic A, Brand M, Fazio VW. The effect of tamoxifen and fenretinide on human colorectal cancer cell lines in vitro. Anticancer Research. 1994;14:2005-2009.

Igawa M, Tanabe T, Chodak GW, Rukstalis DB. N-(4-hydroxyphenyl) retinamide induces cell cycle specific growth inhibition in PC3 cells. The Prostate. 1994;24:299-305.

Hsieh TC, Wu JM. Effects of fenretinide (4-HPR) on prostate LNCaP cell growth, apoptosis, and prostate-specific gene expression. Prostate. 1997;33:97-104.

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