Phase I Mass Balance, PK and Safety Study of 14C-Labeled Belinostat in Patients With Advanced Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Spectrum Pharmaceuticals, Inc
ClinicalTrials.gov Identifier:
NCT01583777
First received: April 19, 2012
Last updated: February 21, 2014
Last verified: February 2014
  Purpose

The purpose of this trial is to study the mass balance, pharmacokinetics (PK), and safety of belinostat following IV administration in patients with a recurrent or progressive malignancy.


Condition Intervention Phase
Advanced Cancer
Drug: Belinostat
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Study for the Evaluation of Excretion (Mass Balance) and Pharmacokinetics of 14C-Labeled Belinostat in Patients With Advanced Cancer

Resource links provided by NLM:


Further study details as provided by Spectrum Pharmaceuticals, Inc:

Primary Outcome Measures:
  • Maximum recovery of the radioactive dose in urine and feces [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • The Concentration of Belinostat in plasma, urine, and feces and its metabolites [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Secondary objectives are to determine the PK of 14C-labeled belinostat in plasma, urine, and feces following IV administration; to determine the relative proportion of 14C-labeled belinostat and its radiolabeled metabolites in plasma, urine, and feces; and to assess the safety of belinostat.


Estimated Enrollment: 6
Study Start Date: September 2013
Estimated Study Completion Date: April 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Belinostat
Open Label
Drug: Belinostat

On Day 1, a single dose of 14C-labeled belinostat (approximately 94 to 105 µCi, 1500 mg) will be administered to the patient as a 30-minute IV infusion.

After Cycle 1 evaluations are completed, and if it is in the best interest of the patient, patients may receive additional cycles of non-radiolabeled belinostat until disease progression, unacceptable toxicity, or initiation of new anticancer therapy. After Cycle 1, Day 21, non radiolabeled belinostat will be administered IV as a 30 -45 minute infusion of 1000 mg/m2 on Days 1 through 5 every 21 days.


Detailed Description:

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.

  Eligibility

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

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 mL/minute.
  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 contraception.
  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.
  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: NCT01583777

Locations
Spain
Hospital Universitario Madrid Sanchinarro
Madrid, Spain, 28050
Sponsors and Collaborators
Spectrum Pharmaceuticals, Inc
Investigators
Study Director: Mi Rim Choi, MD Spectrum Pharmaceuticals, Inc
  More Information

No publications provided

Responsible Party: Spectrum Pharmaceuticals, Inc
ClinicalTrials.gov Identifier: NCT01583777     History of Changes
Other Study ID Numbers: SPI-BEL-12-103
Study First Received: April 19, 2012
Last Updated: February 21, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Spectrum Pharmaceuticals, Inc:
Belinostat

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on July 26, 2014