Clinical trial NCT00559182: A Study of MK-8033 in Patients With Advanced Solid Tumors (MK-8033-001)
Official title: A Phase I Dose Escalation Study of MK-8033 in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Cancer
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2007-11-16
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Safety and tolerability of MK-8033 based on drug-related dose limiting toxicity.
timeFrame: for the entire duration of study (27 months)
measure: Recommended Phase II Dose (RP2D) based on safety, tumor pharmacodynamics, and pharmacokinetics
timeFrame: for the entire duration of study (27 months)
measure: Plasma area under the curve (AUC) for F2 formulation alone or in combination with omeprazole
timeFrame: Day 1-21
measure: Safety and tolerability of MK-8033 F2 formulation alone or in combination with omeprazole based on incidence of adverse experiences
timeFrame: Day 1-21
measure: Tumor Pharmacodynamics (PD): phospho-c-Met (MET or MNNG HOS Transforming gene) Levels (Parts A & B)
timeFrame: Cycle 1 pre-dose & Day 12
measure: Tumor PD: phospho-Akt (Protein Kinase B) Levels (Parts A & B)
timeFrame: Cycle 1 pre-dose & Day 12
measure: Tumor PD: phospho-MAPK (mitogen-activated protein kinase) Levels (Parts A & B)
timeFrame: Cycle 1 pre-dose & Day 12
measure: Bone PD: Cross-Linked N-telopeptides of Type I collagen (NTx) Levels (Parts A & B)
timeFrame: Baseline, Cycle 1 Day 8, & Cycle 3 Day 1
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: Keedy VL, Lenz HJ, Saltz L, Whisenant JG, Berlin JD, Camacho LH. First-in-human phase I dose escalation study of MK-8033 in patients with advanced solid tumors. Invest New Drugs. 2018 Oct;36(5):860-868. doi: 10.1007/s10637-018-0567-z. Epub 2018 Jan 29.