Fenretinide and Safingol in Treating Patients With Relapsed Malignancies

Status: Active

Description

The purpose of this study is to find out what effects (good and bad) an investigational drug, called safingol, has when it is combined with another investigational drug, called fenretinide, in patients with malignant solid tumors or non-Hodgkin lymphoma. The purpose of this study is also to see what the side effects of safingol and fenretinide are when given by vein to research participants. Researchers also want to find out the highest amount of safingol that can be given by vein when given with a specific dose of fenretinide.

Eligibility Criteria

Inclusion Criteria

  • SOLID TUMOR INCLUSION CRITERIA:
  • Patients must have histologically or cytologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
  • All patients must have measurable disease documented by computed tomography (CT), magnetic resonance imaging (MRI), or nonmeasurable disease documented by physical exam within 28 days prior to registration
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2 (Karnofsky >= 60%)
  • Life expectancy of greater than 3 months
  • Absolute neutrophil count >= 1,500/uL
  • Platelets >= 100,000/uL
  • Total bilirubin =< 1.5 x institutional upper limit of normal (IULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 x IULN, =< 5 x IULN for patients with liver metastases
  • Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x IULN, =< 5 x IULN for patients with liver metastases
  • Creatinine within institutional normal limits (WNL) OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; for women of child-bearing potential, a negative serum pregnancy test is required within 72 hours prior to receiving study drug each cycle; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document
  • Patients who have received prior treatment with oral or intravenous fenretinide as a single agent are eligible, provided they did not experience severe toxicity related to fenretinide
  • NON-HODGKIN LYMPHOMA INCLUSION CRITERIA:
  • Patients must have histologically or cytologically confirmed non-Hodgkin’s lymphoma for which standard therapies do not exist or are no longer effective; to be eligible for this study, lymphoma patients must have no marrow involvement as documented by routine marrow aspiration and biopsy performed within 30 days of study entry
  • All patients must have measurable disease documented by CT, MRI, or nonmeasurable disease documented by physical exam within 28 days prior to registration
  • Absolute neutrophil count (ANC) >= 1500 unless due to direct bone marrow involvement of disease
  • Platelets >= 100,000, unless due to direct bone marrow involvement of disease
  • Hemoglobin >= 8.0 gm/dL; transfusion permitted to achieve this level
  • Serum creatinine =< 1.5 x the IULN
  • Total bilirubin =< 1.5 x the IULN
  • AST/ALT =< 2.5 x the IULN or =< 5 x IULN for patients with liver metastases
  • ECOG performance status of 0 - 2 and estimated survival of at least 3 months
  • Patients must be able to understand and agree to sign an institutional review board (IRB)-approved informed consent form
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry, for the duration of study, and for two months after study participation; for women of child-bearing potential, a negative serum pregnancy test is required within 72 hours prior to receiving study drug each cycle; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Patients who have received prior treatment with oral or intravenous fenretinide as a single agent are eligible, provided they did not experience severe toxicity related to fenretinide

Exclusion Criteria

  • Radiation therapy, chemotherapy, and other investigational agents within 3 weeks (6 weeks for nitrosourea or mitomycin C) prior to starting fenretinide + safingol; patients must have recovered from toxicities of prior therapy
  • Concurrent administration of any other investigational agents
  • Uncontrolled intercurrent illnesses including, but not limited to, ongoing or active systemic infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, coagulation disorders; other major medical illnesses of the cardiovascular or respiratory systems or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study; breastfeeding must be discontinued
  • Major surgery in the last three weeks
  • Patients with previously untreated brain metastases (including parenchymal, meningeal or dural-based central nervous system [CNS] lesions) are excluded; however, patients with previously treated (surgery, radiation or both), clinically inactive brain metastases, who have not received corticosteroid therapy within three weeks of starting protocol therapy, are eligible
  • Known allergy to egg products or soy bean oil
  • Patients known to be human immunodeficiency (HIV)-positive receiving anti-retroviral therapy are excluded from the study
  • Baseline fasting triglycerides > 2.5 IULN or hypertriglyceridemia requiring medication; patients requiring medication for other dyslipidemias (i.e., elevated low-density lipoprotein [LDL] cholesterol) are eligible
  • Concomitant use of the following drugs: antioxidants; herbal or other alternative therapy medications; vitamin supplements (especially vitamins A, C, and E) other than a standard dose multivitamin, acetaminophen, cyclosporine A or analogue; verapamil; tamoxifen or analogue, ketoconazole, chlorpromazine; RU486; indomethacin; or sulfinpyrazone, tetracycline, nalidixic acid, nitrofurantoin, phenytoin, sulfonamides, lithium, ceftriaxone, and amiodarone; if the patients discontinue usage of the above drugs, they can be eligible for enrollment into the study after a washout period of four half-lives
  • Poorly-controlled diabetes mellitus, as defined as fasting serum glucose concentration over 200 mg/dl or glycated hemoglobin (A1C) over 7.5%.
  • Patients with an identified familial hyperlipidemia disorder
  • Known history of allergic reactions attributed to compounds of similar chemical or biologic composition to fenretinide, such as 13-cis-retinoic acid, retinol, or all-trans-retinoic acid
  • Patients with esophageal cancer with unresected or recurrent primary tumors in the esophagus are only permitted after discussion of patient with study chair
  • Baseline (pre-treatment) serum troponin T (TnT) >= 0.03 ng/mL; Troponin T levels may be rechecked and therapy given if levels decrease to < 0.03 ng/mL
  • Baseline (pre-treatment) electrocardiogram (EKG) with any of the following changes consistent with cardiac ischemia: *Significant ST depression (ST depression of >= 2 mm, measured from isoelectric line to the ST segment at a point 60 msec from the end of the QRS complex) * Significant ST elevation (> 1mm in limb lead or 2 mm in precordial lead measured at a point 0.04 sec [1 mm] after the J-point [the end of the QRS complex] and compared to baseline [line drawn from P start to T end]) * Investigators are encouraged to consult with cardiologists locally and with the study chair should any questions arise

Locations & Contacts

Texas

Dallas
UT Southwestern / Simmons Cancer Center-Dallas
Status: Active
Contact: David Eric Gerber
Phone: 214-648-4180
Email: david.gerber@utsouthwestern.edu
Lubbock
Covenant Medical Center-Lakeside
Status: Active
Contact: Donald Paul Quick
Phone: 806-725-8000
Email: dquick@covhs.org
Texas Tech University Health Sciences Center-Lubbock
Status: Active
Contact: Min Hee Kang
Phone: 806-743-2694
Email: min.kang@ttuhsc.edu

Trial Objectives and Outline

PRIMARY OBJECTIVE:

I. To determine the maximum tolerated dose (MTD) of an intravenous (emulsion) safingol when administered as a continuous intravenous (c.i.v.) infusion for two days, once every 3 weeks, in combination with fenretinide (4-HPR) intravenous emulsion administered as a continuous intravenous infusion for five days, once every 3 weeks.

II. To describe the toxicities of intravenous (emulsion) safingol when combined with fenretinide (4-HPR) intravenous emulsion.

III. To determine the pharmacokinetics of intravenous (emulsion) safingol in combination with intravenous fenretinide (4-HPR) by analysis of plasma levels of safingol, fenretinide, fenretinide metabolites, and sphingolipid levels.

IV. To determine (within the confines of a phase I clinical trial) preliminary estimates of disease or tumor response to fenretinide (4-HPR) intravenous emulsion in combination with intravenous (emulsion) safingol.

OUTLINE: This is a dose-escalation study of safingol.

Patients receive fenretinide intravenously (IV) continuously on days 1-5 and safingol IV continuously on days 1-2. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
UT Southwestern / Simmons Cancer Center-Dallas

Principal Investigator
David Eric Gerber

Trial IDs

Primary ID SPOC-2010-002
Secondary IDs NCI-2012-00816, SCCC-12Y11, Mod6_STU 042011-132
Clinicaltrials.gov ID NCT01553071