Clinical trial NCT01380184: Pharmacokinetics of Ridaforolimus (MK-8669) in Chinese Participants (MK-8669-059)
Official title: A Study to Assess the Pharmacokinetics of Ridaforolimus in Chinese Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cancer, Advanced
Keywords: Relapsed cancer
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2011-06-27
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Part 1 of the study will assess the pharmacokinetics, safety, and tolerability of ridaforolimus (MK-8669) after administration of single and multiple 40 mg doses in Chinese participants with advanced cancer. Part 2 of the study is optional; participants can continue to receive the study treatment in a weekly regimen of daily oral doses of ridaforolimus 40 mg for five consecutive days followed by two days off-treatment.


Eligibility criteria: Inclusion criteria:

* Chinese descent with all 4 biological grandparents born in China and of Chinese descent.
* Histologically- or cytologically-confirmed metastatic or locally advanced solid tumor or lymphoma that has failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy does not exist.
* Performance status of ≤1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
* Female participants must be post-menopausal.
* Male participants must agree to use a medically-acceptable method of contraception/barrier protection during the study and for 30 days after the last dose of study treatment.
* Participants must be healthy enough to receive the study treatments (that is, meet certain laboratory value parameters).
* Life expectancy of \>3 months.

Exclusion criteria:

* Chemotherapy, radiotherapy, or biological therapy within 4 weeks (6 weeks for nitrosoureas, mitomycin C, and monoclonal antibodies) prior to first dose of study treatment (Part 1/Day 1) or has not recovered from adverse events due to agents administered more than 4 weeks earlier.
* Any other concurrent anti-cancer therapy (except luteinizing hormone releasing hormone \[LHRH\] analogs for prostate cancer).
* Concurrent treatment with immunosuppressive agents, including corticosteroids, at doses greater than those used for replacement therapy.
* Clinically significant abnormality on electrocardiogram (ECG) performed at the screening visit and/or prior to administration of the initial dose of study treatment.
* New York Heart Association (NYHA) Class III or IV congestive heart failure or any other significant history of cardiac disease including: myocardial infarction within the last 6 months; ventricular arrhythmia or acute congestive heart failure within the last 3 months; uncontrolled angina; or uncontrolled hypertension.
* Current participation or participation in a study with an investigational compound or device within 30 days prior to the first dose of study treatment.
* Primary central nervous system tumor, active brain metastases or leptomeningeal carcinomatosis.
* Regular use (including use of any illicit drugs or had a recent history within the last year) of drugs, or alcohol abuse.
* Pregnant or breastfeeding, or expecting to conceive within the projected duration of the study.
* Human Immunodeficiency Virus (HIV)-positive.
* Newly diagnosed (within 3 months before the first dose of study drug) or poorly controlled Type 1 or 2 diabetes.
* Required treatment with medications that are inducers or inhibitors of cytochrome P450 (CYP3A).
* Active infection or use of intravenous (IV) antibiotics, antiviral, or antifungal agents within 2 weeks prior to the first dose of the study treatment.
* Use of or intention to use herbal teas or herbal remedies (including traditional Chinese medicine, St.John's Wort, shark cartilage, etc.) from 2 weeks prior to the first dose and throughout the study.
* Anticipation of need for immunologic therapy, radiation therapy, surgery, or chemotherapy during the study.
* Past high-dose chemotherapy with stem cell rescue.
* Blood transfusion within one week of study entry.
* Inability to swallow capsules and/or documented surgical or anatomical condition that will preclude swallowing and absorbing oral medications on an ongoing basis.
* Known hypersensitivity to the components of the study treatment or its analogs or antibiotics (e.g. clarithromycin, erythromycin, azithromycin).
* Intention to consume grapefruit or grapefruit juice for approximately 2 weeks prior to first dosing until the completion of the study.
* Inadequate recovery from any prior surgical procedure or any major surgical procedure within 4 weeks prior to the first dose of study treatment.

Primary outcomes:
measure: Lag Time (Tlag) of Ridaforolimus: Day 1
timeFrame: Cycle 1 Day 1: Predose and at various time points up to 24 hours postdose on Day 1; Cycle 1 is 19 days
measure: Area Under the Curve From 0 to Infinity (AUC0-∞) of Ridaforolimus: Cycle 1 (Cycle 1 is 19 Days)
timeFrame: Cycle 1: Predose on Day 1 and at various time points through to 24 hours postdose on Day 19; Cycle 1 is 19 days
measure: Area Under the Curve From 0 to 24 Hours (AUC0-24hr) of Ridaforolimus: Day 1, Day 19
timeFrame: Cycle 1 Day 1: Predose and at various time points up to 24 hours postdose on Day 1; Cycle 1 Day 19: Predose and at various time points up to 24 hours postdose on Day 19; Cycle 1 is 19 days
measure: Maximum Concentration (Cmax) of Ridaforolimus: Day 1, Day 19
timeFrame: Cycle 1 Day 1: Predose and at various time points up to 24 hours postdose on Day 1; Cycle 1 Day 19: Predose and at various time points up to 24 hours postdose on Day 19; Cycle 1 is 19 days
measure: Concentration at 24 Hours (C24hr) of Ridaforolimus: Day 1, Day 19
timeFrame: Cycle 1 Day 1: Predose and at various time points up to 24 hours postdose on Day 1; Cycle 1 Day 19: Predose and at various time points up to 24 hours postdose on Day 19; Cycle 1 is 19 days
measure: Time to Maximum Concentration (Tmax) of Ridaforolimus: Day 1, Day 19
timeFrame: Cycle 1 Day 1: Predose and at various time points up to 24 hours postdose on Day 1; Cycle 1 Day 19: Predose and at various time points up to 24 hours postdose on Day 19; Cycle 1 is 19 days
measure: Apparent Terminal Half-life (t1/2) of Ridaforolimus: Cycle 1 (Cycle 1 is 19 Days)
timeFrame: Cycle 1: Predose on Day 1 and at various time points through to 24 hours postdose on Day 19; Cycle 1 is 19 days
Secondary outcomes:
measure: Number of Participants Experiencing Clinical and Laboratory Adverse Events (AEs)
timeFrame: From first dose up to 30 days after last dose (Up to 26 weeks)
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Liu L, Zhang W, Li W, Lv F, Xia Z, Zhang S, Liu W, Zandvliet AS, Waajen S, Zhang LX, Yan L, Li J. A phase I study of ridaforolimus in adult Chinese patients with advanced solid tumors. J Hematol Oncol. 2013 Jul 8;6:48. doi: 10.1186/1756-8722-6-48.