Fenretinide in Treating Patients With Metastatic or Unresectable Malignant Solid Tumors



Status:Recruiting
Conditions:Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - Any
Updated:10/2/2013
Start Date:November 2006

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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.


OBJECTIVES:

- 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
2-6.

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.

DISEASE CHARACTERISTICS:

- 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

PATIENT CHARACTERISTICS:

- 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
following:

- 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

PRIOR CONCURRENT THERAPY:

- 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
following*:

- 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
following:

- 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
7
sites
Pasadena, California 91105
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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...
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Duarte, CA
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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...
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Los Angeles, CA
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2279 45th Street
Sacramento, California 95817
(916) 734-5800
University of California Davis Cancer Center At UC Davis Comprehensive Cancer Center, specialized teams of...
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Sacramento, CA
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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...
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Los Angeles, CA
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2500 Alhambra Ave
Martinez, California 94553
(925) 370-5000
Contra Costa Regional Medical Center Contra Costa Health Services is the largest department of County...
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Martinez, CA
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Odessa, TX
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