A Phase I Dose Escalation Study of MK-8033 in Patients With Advanced Solid Tumors
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 47
- Primary Endpoint
- Safety and tolerability of MK-8033 based on drug-related dose limiting toxicity.
Study Overview
Brief Summary
This is a first-in-human trial to establish the safety, tolerability, Recommended Phase II Dose (RP2D), pharmacodynamic, and clinical activity of MK-8033.
Parts A and B of the study will determine the maximum tolerated dose (MTD) and RP2D. Part C of the study will be a single panel crossover study to determine the effect of omeprazole, a gastric pH modifier, on the pharmacokinetics of MK-8033.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patient must be at least 18 years of age, with adequate organ function, and an Eastern Cooperative Oncology Group (ECOG) performance of <2
- •Patient must be willing to undergo pre-study and post-dose tumor biopsy and have tumor accessible for biopsy (Waived during Parts A and C)
Exclusion Criteria
- •Patient is currently using bisphosphonate therapy or has received this therapy in past 6 months
- •Patient has had chemotherapy, radiotherapy, or biological therapy within 4 weeks of study participation
- •Patient has history of cardiac disease
- •Patient with a primary central nervous system tumor
- •Patient has a known psychiatric or substance abuse disorder
- •Patient is pregnant or breastfeeding, or expecting to conceive during the study
- •Patient is known to be Human Immunodeficiency Virus (HIV) positive and the HIV infection is not well controlled
- •Patient has received therapy with a Proton-Pump Inhibitor, Histamine2-Receptor antagonist or antacid within one week of study participation (Part B only)
Arms & Interventions
Parts A and B: MK-8033
Dose Escalation Study
Intervention: Comparator: MK-8033 (Drug)
Part C: MK-8033 +/- omeprazole
Crossover Study
Intervention: Comparator: MK-8033 +/- omeprazole (Drug)
Outcomes
Primary Outcomes
Safety and tolerability of MK-8033 based on drug-related dose limiting toxicity.
Time Frame: for the entire duration of study (27 months)
Recommended Phase II Dose (RP2D) based on safety, tumor pharmacodynamics, and pharmacokinetics
Time Frame: for the entire duration of study (27 months)
Plasma area under the curve (AUC) for F2 formulation alone or in combination with omeprazole
Time Frame: Day 1-21
Safety and tolerability of MK-8033 F2 formulation alone or in combination with omeprazole based on incidence of adverse experiences
Time Frame: Day 1-21
Tumor Pharmacodynamics (PD): phospho-c-Met (MET or MNNG HOS Transforming gene) Levels (Parts A & B)
Time Frame: Cycle 1 pre-dose & Day 12
Tumor PD: phospho-Akt (Protein Kinase B) Levels (Parts A & B)
Time Frame: Cycle 1 pre-dose & Day 12
Tumor PD: phospho-MAPK (mitogen-activated protein kinase) Levels (Parts A & B)
Time Frame: Cycle 1 pre-dose & Day 12
Bone PD: Cross-Linked N-telopeptides of Type I collagen (NTx) Levels (Parts A & B)
Time Frame: Baseline, Cycle 1 Day 8, & Cycle 3 Day 1
Secondary Outcomes
No secondary outcomes reported