Pharmacokinetics of Ridaforolimus (MK-8669) in Chinese Participants (MK-8669-059)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 1

Conditions: Cancer, Advanced

Treatments: Drug: ridaforolimus

Study type: Interventional

Funder types: Industry

Identifiers

NCT01380184

MK-8669-059 (Other Identifier)

8669-059

Details and patient eligibility

About

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.

Enrollment: 15 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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15 participants in 1 patient group

Ridaforolimus 40 mg

Experimental group

Description:

In Part 1 (Days 1-19), participants received ridaforolimus (MK-8669) 40 mg via oral enteric-coated tablet on Day 1; followed by no study treatment on Days 2-7; followed by two weekly sequences (Days 8-19) consisting of 5 consecutive days of ridaforolimus 40 mg and 2 consecutive days off study treatment. Following Part 1, participants underwent at least a 2-day study treatment washout prior to starting Part 2. In Part 2, participants received a weekly treatment regimen consisting of 5 consecutive days (Days 1-5) of ridaforolimus 40 mg via oral enteric-coated tablet and 2 consecutive days (Days 6-7) off study treatment. This weekly treatment regimen was repeated every subsequent week for the remainder of participation in Part 2.

Treatment:

Drug: ridaforolimus