Oral Bioavailability and Mass Balance Trial With Pimasertib

This study has been completed.
Sponsor:
Collaborator:
Merck Serono S.A., Switzerland
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT01713036
First received: September 13, 2012
Last updated: May 12, 2014
Last verified: May 2014
  Purpose

This is a Phase 1, open-label, single centered trial to evaluate the mass balance, bioavailability and metabolism of pimasertib in cancer subjects with locally advanced or metastatic solid tumors.


Condition Intervention Phase
Locally Advanced or Metastatic Solid Tumors
Drug: Pimasertib
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I, Open-Label, Single Center Trial to Investigate the Mass Balance, Metabolite Profile and Oral Bioavailability of Pimasertib in Cancer Patients With Locally Advanced or Metastatic Solid Tumors

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Oral bioavailability of pimasertib: Area under the curve (AUC) of unlabeled pimasertib administered per os (PO) and intravenous (IV) single tracer dose of [14C] pimasertib [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • Mass Balance: Recovery of total [14C] radioactivity in excreta, that is, Ae0-t in urine and in feces [ Time Frame: Day 8-21 ] [ Designated as safety issue: No ]
  • Metabolite Identification: Chemical structure of pimasertib metabolites in plasma, urine, and feces [ Time Frame: Day 8-21 ] [ Designated as safety issue: No ]
  • Plasma concentration profiles: Plasma concentrations of [14C] pimasertib and its metabolites [ Time Frame: Day 8 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pharmacokinetic (PK) parameters: Cmax, tmax, λz, t1/2, CL, CL/f, Vz, VC, Vz/f for unlabeled pimasertib and IV single tracer dose of [14C] pimasertib [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
  • PK parameters: Cmax, tmax, AUC0-t, AUC0-∞, Ae0-t, λz, t1/2, CL/f, Vz/f of total radioactivity following single dose pimasertib spiked with [14C] pimasertib [ Time Frame: Day 8 ] [ Designated as safety issue: No ]
  • Pimasertib plasma protein binding [ Time Frame: Day 8 ] [ Designated as safety issue: No ]
  • Total radioactivity ratio blood/plasma [ Time Frame: Day 8 ] [ Designated as safety issue: No ]
  • Anti-tumor activity defined as CR, PR, or SD and PD based on the Investigator tumor evaluations performed every 2 cycles in accordance with Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v.1.1) [ Time Frame: Cycle 3, 5, 7 and thereafter every alternate cycle up to 4 weeks after last study dose ] [ Designated as safety issue: No ]
  • Number of subjects with treatment emergent adverse events (TEAEs) [ Time Frame: Baseline up to 4 weeks after last study dose ] [ Designated as safety issue: No ]

Enrollment: 11
Study Start Date: November 2012
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pimasertib Drug: Pimasertib
Unlabeled pimasertib, 60 milligram (mg), will be administered as oral capsules in the morning of Day 1 of Part A of the study (21-day treatment period). After 1 hour, the intravenous tracer dose of [14C] pimasertib (2 microgram [mcg] equaling 9 kilobecquerel [kBq]) will be administered as a bolus injection on Day 1. From Days 3-21, 60 mg unlabeled pimasertib oral capsules will be administered twice a day except on Day 8, on which 60 mg unlabeled pimasertib capsules spiked with 2.6 megabecquerel (MBq) of [14C] pimasertib will be administered orally in morning followed by an evening dose of 60 mg pimasertib as unlabeled pimasertib oral capsules. Unlabeled pimasertib, 60 mg will be administered as oral capsule twice a day in Part B of the study, that is, cycles of 21 days duration until disease progression, unacceptable toxicity, withdrawal by subject, lost to follow up, or death.
Other Names:
  • MSC19363639B
  • AS703026

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male subject with pathologically confirmed solid tumor preferentially including, but not limited to pancreatic, thyroid, colorectal, lung, and renal cancer, or melanoma which is locally advanced or metastatic, and either refractory to the respective standard therapy for the disease or for which no effective standard therapy is available
  2. Subject has measurable and evaluable disease as defined by RECIST v.1.1
  3. Age greater than or equal to 18 years and less than or equal to 65 years
  4. Body mass index greater than or equal to 19 and less than or equal to 30 kilogram per meter square (kg/m^2)
  5. Subject has Eastern Cooperative Oncology Group Performance Status (ECOG PS) of less than or equal to 1
  6. Male subjects with female partners of childbearing potential must be willing to use an adequate method of contraception during and for 4 weeks after the last dose of the trial medication. During this time, female partners should use a contraceptive method with a failure rate of less than 1 percent
  7. Subject has read and understood the informed consent form and is willing and able to give written informed consent before any trial related procedures are performed

Exclusion Criteria:

  1. Bone marrow impairment as evidenced by hemoglobin less than 10.0 gram per deciliter (g/dL), neutrophil count less than 1.5 * 10^9 per liter (/L), and/or platelets less than 100 * 10^9/L
  2. Renal impairment as evidenced by serum creatinine greater than 1.5 * upper limit of normal (ULN) and calculated creatinine clearance less than 60 milliliter per minute (mL/min) (Cockcroft Gault formula)
  3. Liver function and liver cell integrity abnormality as defined by total bilirubin greater than 1.5 * ULN, or aspartate transaminase (AST)/alanine transaminase (ALT) greater than 2.5 * ULN, for subjects with liver metastases AST/ALT greater than 5 * ULN
  4. Primary brain tumors or clinical evidence of active brain metastasis. Subjects with a history of previously treated brain tumor are eligible provided that 1 month following treatment they were stable by computed tomography (CT) scan without evidence of cerebral edema, and have no requirements for anticonvulsants or high doses of corticosteroids
  5. History of gastrointestinal disease, malabsorption syndrome or difficulty in swallowing, which in the investigator's opinion might impair the absorption of pimasertib
  6. Any gastric, small or large bowel surgery that may impact the absorption of pimasertib
  7. Known human immunodeficiency virus (HIV) positivity, active hepatitis
  8. Chemotherapy, radiotherapy, immunotherapy, or molecular targeted cancer therapy within the past 4 weeks or within 5 half-lives of the given drug, whatever is longer, prior to start of trial medication or concomitantly within this trial. This restriction does not apply to steroids and bisphosphonates
  9. Major surgical procedure within the last 8 weeks prior to start of trial medication
  10. History of uveitis and scleritis. Retinal pathology beyond normal age-related processes
  11. History of glaucoma. Subjects are excluded if intraocular pressure is above 21 millimeter of mercury (mmHg)
  12. Evidence of a retinal vein occlusion (RVO) on fluorescein angiogram or a history of RVO. Subjects are also excluded if on examination an ophthalmologist finds that their optic disc is at risk for a central RVO
  13. Life expectancy of less than 12 weeks
  14. Clinically relevant non-malignant disease which in the investigator's opinion would exclude the subject from the trial, such as significant cardiovascular, pulmonary, endocrine, renal and neurological disease or psychiatric disorder
  15. Treatment with strong inhibitors and/or inducers of cytochrome P450 2C19 (CYP2C19) and cytochrome P450 3A4 (CYP3A4). Consumption of CYP3A4 enzyme inducing or inhibiting herbal drugs, fruit juices and beverages (example, grapefruit, grapefruit juice, quinine [tonic water], star fruit, St John's Wort) within 2 weeks prior to start of trial medication until the end of Day 21
  16. Participation in a drug trial within 30 days prior to start of trial medication. Participation in a trial involving administration of [14C] labeled compound(s) within last 6 months prior to start of trial medication
  17. Known hypersensitivity to any of the excipients used
  18. Inability to understand the protocol requirements, instructions and trial-related restrictions, the nature, scope, and possible consequences of the trial
  19. Legal incapacity or limited legal capacity
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01713036

Locations
Hungary
Research Site
Budapest, Hungary
Sponsors and Collaborators
Merck KGaA
Merck Serono S.A., Switzerland
Investigators
Study Director: Medical Responsible Merck KGaA
  More Information

No publications provided

Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT01713036     History of Changes
Other Study ID Numbers: EMR 200066-008, 2012-002562-12
Study First Received: September 13, 2012
Last Updated: May 12, 2014
Health Authority: Hungary: National Institute for Quality and Organizational Development in Healthcare and Medicines

Keywords provided by Merck KGaA:
Mass balance, bioavailability, cancer, 14C

ClinicalTrials.gov processed this record on July 29, 2014