Oral Bioavailability and Mass Balance Trial With Pimasertib

Merck KGaA (EMD Serono)

Status and phase

Completed

Phase 1

Conditions

Locally Advanced or Metastatic Solid Tumors

Treatments

Drug: Pimasertib

Study type

Interventional

Funder types

Industry

Identifiers

NCT01713036

2012-002562-12 (EudraCT Number)

EMR 200066-008

Details and patient eligibility

About

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.

Enrollment

6 patients

Sex

Male

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

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