Fenretinide in Treating Patients With Metastatic or Unresectable Malignant Solid Tumors

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
California Cancer Consortium
ClinicalTrials.gov Identifier:
NCT00387504
First received: October 12, 2006
Last updated: September 10, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Drug: fenretinide
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Trial of Intravenous Fenretinide (4-HPR) for Patients With Malignant Solid Tumors

Resource links provided by NLM:


Further study details as provided by California Cancer Consortium:

Primary Outcome Measures:
  • Maximum tolerated dose (MTD) of fenretinide [ Time Frame: at end of study ] [ Designated as safety issue: Yes ]
  • 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 [ Time Frame: ongoing ] [ Designated as safety issue: Yes ]
  • Survival and time to failure as measured by Kaplan-Meier [ Time Frame: at end of study ] [ Designated as safety issue: No ]

Estimated Enrollment: 21
Study Start Date: November 2006
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    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
Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00387504

Locations
United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
Childrens Hospital Los Angeles
Los Angeles, California, United States, 90027-0700
USC/Norris Comprehensive Cancer Center and Hospital
Los Angeles, California, United States, 90089-9181
Contra Costa Regional Medical Center
Martinez, California, United States, 94553
City of Hope Medical Group
Pasadena, California, United States, 91105
University of California Davis Cancer Center
Sacramento, California, United States, 95817
United States, Texas
Texas Tech University Health Sciences Center
Lubbock, Texas, United States, 79430
Sponsors and Collaborators
California Cancer Consortium
Investigators
Study Chair: Jacek Pinski, MD University of Southern California
  More Information

Additional Information:
No publications provided

Responsible Party: California Cancer Consortium
ClinicalTrials.gov Identifier: NCT00387504     History of Changes
Other Study ID Numbers: CDR0000508770, U01CA062505, CCC-PHI-54, NCI-7540
Study First Received: October 12, 2006
Last Updated: September 10, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by California Cancer Consortium:
unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on October 16, 2014