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

Phase 1
18 Years
Open (Enrolling)
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

Phase I Trial of Intravenous Fenretinide (4-HPR) for Patients With 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.

Inclusion Criteria


- 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

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose (MTD) of fenretinide

Outcome Time Frame:

at end of study

Safety Issue:


Principal Investigator

Jacek Pinski, MD

Investigator Role:

Study Chair

Investigator Affiliation:

USC/Norris Comprehensive Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

November 2006

Completion Date:

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • unspecified adult solid tumor, protocol specific
  • Neoplasms



USC/Norris Comprehensive Cancer Center and Hospital Los Angeles, California  90033-0804
University of California Davis Cancer Center Sacramento, California  95817
City of Hope Comprehensive Cancer Center Duarte, California  91010
Childrens Hospital Los Angeles Los Angeles, California  90027
City of Hope Medical Group Pasadena, California  91105
Contra Costa Regional Medical Center Martinez, California  94553-3156
Texas Tech University Health Sciences Center Lubbock, Texas  79430