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A Phase 1 Study for the Evaluation of Excretion (Mass Balance) and Pharmacokinetics of 14C-Labeled Belinostat in Patients With Advanced Cancer

Phase 1
18 Years
Not Enrolling
Advanced Cancer

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Trial Information

A Phase 1 Study for the Evaluation of Excretion (Mass Balance) and Pharmacokinetics of 14C-Labeled Belinostat in Patients With Advanced Cancer

This is a Phase 1, open-label, single-dose study of 14C-labeled belinostat to determine
routes of elimination of belinostat. A single dose of 14C-labeled belinostat (approximately
94.3 to 105 µCi, 1500 mg) will be administered as a 30-minute IV infusion to the patient.
Routes of elimination of belinostat and its metabolites will be assessed by estimating the
recovery of total radioactivity and parent belinostat over a period of 7 days. Plasma
samples will be taken for 3 days at specified intervals for PK assessments. Total
radioactivity in plasma, urine, and feces will be determined by liquid scintillation
counting. Concentrations of belinostat in plasma and urine will be determined using a
validated liquid chromatography - tandem mass spectroscopy (LC-MS/MS) method. Selected
plasma, urine, and feces samples will be retained for use in the metabolism investigation.
Samples will be initially analyzed using radio-high performance liquid chromatography (HPLC)
to determine the number and relative proportion of belinostat and metabolites present.
Selected samples will be subsequently analyzed using LC-MS to identify the major metabolites
(> 10% of parent area under the curve [AUC]). If it is in the interest of the patient,
treatment with non-radiolabeled belinostat may be continued with 21-day cycles until disease
progression, initiation of new anticancer therapy, or an adverse event (AE) that may affect
patient participation.

Inclusion Criteria:

1. Signed informed consent document indicating understanding of the purpose of and
procedures required for the study and willingness to participate in the study.

2. Histological confirmation of cancer and refractory or intolerant to standard therapy
or cancer for which no standard therapy exists.

3. Age at study entry of 18 years or older.

4. Availability to stay in the research unit for the first 7 days.

5. Adequate renal function defined as a calculated creatinine clearance (CrCl) of > 45

6. Adequate hepatic function: total bilirubin < 1.5 x the upper limits of normal (ULN),
aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x ULN.

7. Adequate hematopoietic function defined as an absolute neutrophil count (ANC) > 1000
cells/µL and platelet count > 50,000/µL.

8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

9. Life expectancy of at least 12 weeks.

10. If female, patient must be postmenopausal for at least 1 year, documented surgically
sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy), or of
childbearing potential and practicing birth control. Acceptable contraceptive methods
in this study are intrauterine device; diaphragm or condom in combination with
spermicidal foam or jelly; injectable, implantable, or transdermal patch; or oral

11. Female patients must have a negative pregnancy test at the Screening Visit and at the
end of study treatment (30 days after the last dose of belinostat).

Exclusion Criteria:

1. Known anal or urinary incontinence.

2. Diagnosis of acute myelogenous leukemia (AML), multiple myeloma, primary hepatic or
renal carcinomas.

3. Inability to consume oral fluids.

4. Treatment with drugs known to inhibit metabolic pathways (glucuronidation, CYP
system) in the 4 weeks before the Screening Visit.

5. Concurrent treatment with diuretics or laxatives.

6. Radiotherapy involving mouth, esophagus, and gastrointestinal tract in the 4 weeks
before the Screening Visit.

7. Polymorphism in UGT1A1.

8. Known diagnosis of human immunodeficiency virus (HIV), hepatitis B or C.

9. Previous participation in a study utilizing 14C.

10. Body surface area < 1.5 m2.

11. Ongoing or medical history of a physical or psychiatric illness, significant
comorbidity, or any medical disorder other than cancer that may require treatment or
make the subject unlikely to fully complete the study.

12. Use of another investigational product or anticancer agent within 4 weeks prior to
the Screening Visit.

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum recovery of the radioactive dose in urine and feces

Outcome Description:

The route of elimination of belinostat will be determined by the recovery of total radioactivity (parent drug and metabolites) and unmetabolized belinostat in urine and feces following single IV administration of 14C-labeled belinostat in patients with recurrent or progressive malignancy.

Outcome Time Frame:

6 months

Safety Issue:


Principal Investigator

Emiliano Calvo, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Hospital Universitario Madrid Sanchinarro


United States: Food and Drug Administration

Study ID:




Start Date:

July 2013

Completion Date:

March 2014

Related Keywords:

  • Advanced Cancer
  • Belinostat
  • Neoplasms