Fenretinide in Treating Patients With Metastatic or Unresectable Malignant Solid Tumors

Therapuetic Areas:Oncology
Age Range:18 - Any
Start Date:November 2006

Use our guide to learn which trials are right for you!

Phase I Trial of Intravenous Fenretinide (4-HPR) for Patients With Malignant Solid Tumors

RATIONALE: Drugs used in chemotherapy, such as fenretinide, work in different ways to stop
the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase I trial is studying the side effects and best dose of fenretinide in
treating patients with metastatic or unresectable malignant solid tumors.


- Determine the maximum tolerated dose of fenretinide in patients with metastatic or
unresectable malignant solid tumors.

- Determine the toxic effects of this drug in these patients.

- Determine the pharmacokinetics and in vivo activity of this drug in these patients.

- Determine, preliminarily, disease or tumor response in patients treated with this drug.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive fenretinide IV continuously on days 1-5. Treatment repeats every 3 weeks
for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients
who achieve a complete or partial response may continue to receive fenretinide at the
discretion of the study chair.

Cohorts of 3-6 patients receive escalating doses of fenretinide until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6
patients experience dose-limiting toxicity. At least 6 patients are treated at the MTD.

Patients undergo blood sample collection to determine plasma concentrations
(pharmacokinetics) of fenretinide periodically during course 1 and at the end of courses

After completion of study treatment, patients are followed every 3 months for 2 years, every
6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 21 patients will be accrued for this study.


- Histologically or cytologically confirmed solid tumor malignancy

- Metastatic and/or unresectable disease

- No standard curative or palliative measures exist or remain effective

- Measurable or evaluable disease

- No known brain metastases unless previously resected or irradiated with no treatment
with steroids for more than 1 month


- ECOG performance status (PS) 0-2 or Karnofsky PS 60-100%

- Life expectancy > 3 months

- WBC ≥ 3,000/mm³

- Absolute neutrophil count ≥ 1,500/mm³

- Platelet count ≥ 75,000/mm³

- Bilirubin < 1.5 times upper limit of normal (ULN)

- AST and ALT ≤ 2.5 times ULN (5 times ULN for patients with known liver metastases)

- Creatinine normal OR creatinine clearance ≥ 60 mL/min

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception prior to, during, and for ≥ 6
months after completion of study treatment

- No uncontrolled diabetes mellitus at high risk for hypertriglyceridemia (i.e.,
fasting serum glucose concentration > 200 mg/dL OR hemoglobin A1C > 7.5%)

- No egg allergy

- No history of allergic reactions to compounds of similar chemical or biologic
composition to fenretinide (e.g., isotretinoin, vitamin A, or tretinoin)

- No uncontrolled intercurrent illness including, but not limited to, any of the

- Ongoing or active infection

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia

- Psychiatric illness or social situation that would preclude compliance with
study requirements

- No known hypertriglyceridemia requiring medication

- No identified familial hyperlipidemia disorder


- Recovered from all prior therapy

- Prior treatment with oral fenretinide is allowed provided no severe toxicity occurred

- At least 2 weeks since prior major surgery

- More than 4 weeks since prior chemotherapy or radiotherapy

- At least 6 weeks since prior nitrosoureas or mitomycin C

- No other concurrent investigational agents

- No other concurrent anticancer chemotherapy

- No other concurrent antioxidants*

- No concurrent hormone-ablative agents, including steroids, except for adrenal
replacement or anti-inflammatory indications

- No other concurrent anticancer agents or therapies

- No concurrent herbal or other alternative therapies*

- No concurrent vitamin supplements (e.g., vitamin A, ascorbic acid, or vitamin E)*

- Standard-dose multivitamin allowed

- No other concurrent medications that may act as modulators of intracellular ceramide
levels or ceramide cytotoxicity, sphingolipid transport, p-glycoprotein, multidrug
resistance protein 1 (MRP1), or MRP1 drug/lipid transporters, including any of the

- Cyclosporine or any of its analogues

- Verapamil

- Tamoxifen or its analogue

- Ketoconazole

- Chlorpromazine

- Mifepristone

- Indomethacin

- Sulfinpyrazone NOTE: *Patients who have discontinued these drugs for ≥ 1 week
are eligible

- No concurrent medications that may cause pseudotumor cerebri, including any of the

- Tetracycline

- Nalidixic acid

- Nitrofurantoin

- Phenytoin

- Sulfonamides

- Lithium

- Amiodarone

- No concurrent total parenteral nutrition (TPN) with intralipids

- No concurrent combination antiretroviral therapy for HIV-positive patients
We found this trial at
1500 E Duarte Rd
Duarte, California 91010
(626) 256-4673
City of Hope Comprehensive Cancer Center City of Hope is a leading research and treatment...
Duarte, CA
Click here to add this to my saved trials
4650 Sunset Blvd
Los Angeles, California 90027
 (323) 660-2450
Childrens Hospital Los Angeles Children's Hospital Los Angeles is a 501(c)(3) nonprofit hospital for pediatric...
Los Angeles, CA
Click here to add this to my saved trials
2279 45th Street
Sacramento, California 95817
(916) 734-5800
University of California Davis Cancer Center At UC Davis Comprehensive Cancer Center, specialized teams of...
Sacramento, CA
Click here to add this to my saved trials
1441 Eastlake Ave
Los Angeles, California 90033
(323) 865-3000
U.S.C./Norris Comprehensive Cancer Center The USC Norris Comprehensive Cancer Center, located in Los Angeles, is...
Los Angeles, CA
Click here to add this to my saved trials
2500 Alhambra Ave
Martinez, California 94553
(925) 370-5000
Contra Costa Regional Medical Center Contra Costa Health Services is the largest department of County...
Martinez, CA
Click here to add this to my saved trials
Odessa, TX
Click here to add this to my saved trials
Pasadena, California 91105
Pasadena, CA
Click here to add this to my saved trials