Clinical trial NCT00589381: Fenretinide Lym-X-Sorb™ in Treating Patients With Recurrent or Resistant Solid Tumors or Lymphoma
Official title: Phase I Trial of Fenretinide (4-HPR, NSC 374551) Lym-X-Sorb™ (LXS) Oral Powder (4-HPR/LXS Oral Powder) (4-HPR) in Adults With Solid Tumors and Lymphomas
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lymphoma
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: unspecified adult solid tumor, protocol specific
recurrent adult Hodgkin lymphoma
recurrent adult T-cell leukemia/lymphoma
anaplastic large cell lymphoma
angioimmunoblastic T-cell lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
recurrent mycosis fungoides/Sezary syndrome
recurrent adult grade III lymphomatoid granulomatosis
adult nasal type extranodal NK/T-cell lymphoma
Waldenström macroglobulinemia
recurrent adult Burkitt lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent mantle cell lymphoma
recurrent marginal zone lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
recurrent small lymphocytic lymphoma
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-01-09
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as fenretinide Lym-X-Sorb™ , work in different ways to stop the growth of cancer 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 Lym-X-Sorb™ in treating patients with recurrent or resistant solid tumors or lymphoma.

Detailed description: OBJECTIVES:

Primary

* To determine the maximum tolerated dose of fenretinide Lym-X-Sorb™ oral powder (4-HPR/LXS oral powder) in patients with recurrent and/or resistant solid tumors or lymphomas.
* To define the toxicities of 4-HPR/LXS oral powder in these patients.
* To determine the plasma pharmacokinetics of 4-HPR/LXS oral powder in these patients.

Secondary

* To determine the level of fenretinide delivered as 4-HPR/LXS oral powder in normal peripheral blood mononuclear cells.

OUTLINE: This is a multicenter study.

Patients receive oral fenretinide Lym-X-Sorb™ oral powder (4-HPR/LXS oral powder) (mixed in food carriers) three times daily on days 1-7. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving stable disease response or better may receive additional courses of treatment at the discretion of the treating physician and principal investigator.

Blood samples are collected periodically for pharmacokinetic and pharmacodynamic studies.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed (by the NIH pathology department) diagnosis of 1 of the following:

  * Solid tumor malignancy that is metastatic or unresectable
  * Lymphoma for which standard treatment or curative measures do not exist, or are associated with minimal patient survival benefit
* Recurrent and/or resistant disease
* Measurable or evaluable disease
* No known brain metastases

  * Patients whose brain metastatic disease status has remained stable for ≥ 3 months after treatment may be eligible at the discretion of the principal investigator (without steroids or anti-seizure medications)

PATIENT CHARACTERISTICS:

* ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
* Life expectancy ≥ 3 months
* Absolute neutrophil count ≥ 1,500/µL
* Platelets ≥ 100,000/µL (CTCAE v.3 grade 1 thrombocytopenia allowed if explained by involvement of the bone marrow by lymphoma)
* Total bilirubin ≤ 1.5 times normal institutional limits (2.5 mg/dL for patients with Gilbert's syndrome)
* AST (SGOT)/ALT (SGPT) ≤ 2.5 times upper limit of normal (ULN)
* Creatinine \< 1.5 times ULN OR creatinine clearance ≥ 60 mL/min
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use two methods of birth control, including at least one highly effective method (e.g., intrauterine device \[IUD\], hormonal birth control pills/injections/implants, tubal ligation or partner's vasectomy), and one additional effective method (e.g., latex condoms, diaphragm, or cervical cap), prior to, during, and for 2 months after completion of study treatment

  * Men must use a latex condom every time they have sexual intercourse during therapy and for 2 months after discontinuing fenretinide, even if they have had a successful vasectomy
* No clinically significant illnesses which could compromise participation in the study, including, but not limited to, any of the following:

  * Active or uncontrolled infection
  * Immune deficiencies or confirmed diagnosis of HIV infection
  * Uncontrolled diabetes
  * Uncontrolled hypertension
  * Symptomatic congestive heart failure
  * Unstable angina pectoris
  * Myocardial infarction within the past 6 months
  * Uncontrolled cardiac arrhythmia
  * Psychiatric illness/social situations that would limit compliance with study requirements
* No known wheat gluten allergy or allergy or sensitivity to the study drug
* No history of pancreatitis as evidenced by elevated amylase or lipase ≥ grade 2 and accompanied by symptoms of pancreatitis (e.g., abdominal pain)

PRIOR CONCURRENT THERAPY:

* Recovered from adverse events and/or toxicity due to prior chemotherapy or biologic therapy
* No chemotherapy or biologic therapy within 4 weeks prior to entering the study (6 weeks for nitrosoureas, mitomycin C, or UCN-01)
* At least 1 month since any prior radiotherapy or major surgery
* At least 2 weeks since any prior administration of study drug in an exploratory IND/phase 0 study
* Patients receiving bisphosphonates for any cancer or undergoing androgen deprivation therapy for prostate cancer are eligible for this therapy
* No concurrent sulfonamides
* No other concurrent investigational agents
* No other concurrent cancer chemotherapy, or immunomodulating agents (including systemic corticosteroids)
* Patients must not take any drugs suspected of causing pseudo tumor cerebri, including any of the following:

  * Tetracycline
  * Nalidixic acid
  * Nitrofurantoin
  * Phenytoin
  * Sulfonamides
  * Lithium
  * Amiodarone
  * Vitamin A (except as part of routine total parenteral nutrition vitamin supplements or in a single daily standard dose oral multivitamin supplement)
* No concurrent herbal supplements or other alternative therapy medications

Primary outcomes:
measure: Maximum tolerated dose of 4-HPR/LXS oral powder
measure: Safety
measure: Toxicity
Secondary outcomes:
measure: Level of fenretinide in normal peripheral blood mononuclear cells
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Childrens Hospital Los Angeles
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center and Hospital
state: California
city: Fort Lauderdale
country: United States
facility: Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital
state: Florida
city: Bethesda
country: United States
facility: Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
state: Maryland
Study officials:
affiliation: NCI - Medical Oncology Branch
name: Shivaani Kummar, MD
role: STUDY_CHAIR
References:
citation: Kummar S, Gutierrez ME, Maurer BJ, Reynolds CP, Kang M, Singh H, Crandon S, Murgo AJ, Doroshow JH. Phase I trial of fenretinide lym-x-sorb oral powder in adults with solid tumors and lymphomas. Anticancer Res. 2011 Mar;31(3):961-6.