Oral Bioavailability and Mass Balance Trial With Pimasertib
Condition: Locally Advanced or Metastatic Solid Tumors
Intervention: Pimasertib
Intervention description: Part A: Subjects will receive unlabeled pimasertib capsules orally at a single dose of 60 milligram (mg) on Day 1. One hour after administration of the oral unlabeled pimasertib dose, the intravenous (IV) tracer dose of 9 kilobecquerel (kBq) [14C] pimasertib will be administered as a bolus injection. On Days 3-21 (except Day 8), subjects will receive unlabeled pimasertib capsules orally at a dose of 60 mg twice daily (BID). In the morning of Day 8, subjects will receive 60 mg unlabeled pimasertib capsules spiked with a dose of 2.6 megabecquerel (MBq) (70 microcuries [mcgCi]) of [14C] pimasertib orally. In the evening of Day 8, subjects will receive the evening dose of 60 mg pimasertib as unlabeled pimasertib capsules orally. Part B : Subjects will be administered with 60 mg BID unlabeled pimasertib as oral capsules continuously in cycles of 21 days until progression of the disease, unacceptable toxicity, withdrawal of consent by the subject, loss to follow-up or death.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: Male
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Mass balance, bioavailability, cancer, 14C

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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

          -  Subject has measurable and evaluable disease as defined by Response Evaluation
             Criteria In Solid Tumors version 1.1 (RECIST v.1.1)

          -  Age greater than or equal to 18 years and less than or equal to 65 years

          -  Body mass index greater than or equal to 19 and less than or equal to 30 kilogram per
             meter square (kg/m^2)

          -  Subject has Eastern Cooperative Oncology Group Performance Status (ECOG PS) of less
             than or equal to 1

          -  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

          -  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:

          -  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

          -  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)

          -  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

          -  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

          -  History of gastrointestinal disease, malabsorption syndrome or difficulty in
             swallowing, which in the investigator's opinion might impair the absorption of
             pimasertib

          -  Any gastric, small or large bowel surgery that may impact the absorption of pimasertib

          -  Known human immunodeficiency virus (HIV) positivity, active hepatitis

          -  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

          -  Major surgical procedure within the last 8 weeks prior to start of trial medication

          -  History of uveitis and scleritis. Retinal pathology beyond normal age-related
             processes

          -  History of glaucoma. Subjects are excluded if intraocular pressure is above 21
             millimeter of mercury (mmHg)

          -  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

          -  Life expectancy of less than 12 weeks

          -  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

          -  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

          -  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

          -  Known hypersensitivity to any of the excipients used

          -  Inability to understand the protocol requirements, instructions and trial-related
             restrictions, the nature, scope, and possible consequences of the trial

          -  Legal incapacity or limited legal capacity