fenretinide in treating patients with metastatic or unresectable malignant solid tumors

Conditions: Unspecified Adult Solid Tumor, Protocol Specific

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.

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 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

Keywords: unspecified adult solid tumor, protocol specific