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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

Phase 1
18 Years
65 Years
Open (Enrolling)
Locally Advanced or Metastatic Solid Tumors

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Trial Information

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

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

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 *

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

6. Any gastric, small or large bowel surgery that may impact the absorption of

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

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

Type of Study:


Study Design:

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

Outcome Measure:

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

Outcome Time Frame:

Day 1

Safety Issue:


Principal Investigator

Medical Responsible

Investigator Role:

Study Director

Investigator Affiliation:

Merck KGaA


Hungary: National Institute for Quality and Organizational Development in Healthcare and Medicines

Study ID:

EMR 200066-008



Start Date:

October 2012

Completion Date:

June 2013

Related Keywords:

  • Locally Advanced or Metastatic Solid Tumors
  • Mass balance, bioavailability, cancer, 14C