Fenretinide in Treating Patients With Metastatic or Unresectable Malignant Solid Tumors

Unspecified Adult Solid Tumor, Protocol Specific Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00387504
• Other study ID #: CDR0000508770
• Secondary ID: U01CA062505CCC-P
• Status: Completed
• Phase: Phase 1
• First received: October 12, 2006
• Last updated: September 10, 2013
• Start date: November 2006

Study information

• Verified date: September 2013
• Source: California Cancer Consortium
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Neoplasms
• Unspecified Adult Solid Tumor, Protocol Specific

Intervention

Drug:
• fenretinide
4-HPR (Fenretinide) is given as a continuous intravenous infusion (CIV) for five consecutive days. Cycle is repeated every 3 weeks, if PR, CR or stable disease for 6 cycles.

Other:
• pharmacological study
samples drawn per protocol

Locations

Country	Name	City	State
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Childrens Hospital Los Angeles	Los Angeles	California
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California
United States	Texas Tech University Health Sciences Center	Lubbock	Texas
United States	Contra Costa Regional Medical Center	Martinez	California
United States	City of Hope Medical Group	Pasadena	California
United States	University of California Davis Cancer Center	Sacramento	California

Sponsors (2)

Lead Sponsor	Collaborator
California Cancer Consortium	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose (MTD) of fenretinide		at end of study	Yes
Primary	Toxicity as measured by type (organ affected or laboratory determination such as absolute neutrophil count), severity (NCI CTCAE v3.0), time of onset (course number), duration, and reversibility or outcome		ongoing	Yes
Primary	Survival and time to failure as measured by Kaplan-Meier		at end of study	No