A Study of MK-8033 in Patients With Advanced Solid Tumors (MK-8033-001)

Phase 1

Completed

• Conditions: Advanced Cancer

• Registration Number: NCT00559182
• Lead Sponsor: Merck Sharp & Dohme LLC

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2007-11-14
• Study First Submitted QC: 2007-11-14
• Study First Posted: 2007-11-16
• Study Start: 2007-12-05
• Primary Completion: 2010-06-10
• Study Completion: 2010-07-09
• Status Verified: 2022-07
• Last Update Submitted: 2022-07-22
• Last Update Posted: 2022-07-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 47

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)

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Safety and tolerability of MK-8033 based on drug-related dose limiting toxicity.	for the entire duration of study (27 months)
Recommended Phase II Dose (RP2D) based on safety, tumor pharmacodynamics, and pharmacokinetics	for the entire duration of study (27 months)
Plasma area under the curve (AUC) for F2 formulation alone or in combination with omeprazole	Day 1-21
Safety and tolerability of MK-8033 F2 formulation alone or in combination with omeprazole based on incidence of adverse experiences	Day 1-21
Tumor Pharmacodynamics (PD): phospho-c-Met (MET or MNNG HOS Transforming gene) Levels (Parts A & B)	Cycle 1 pre-dose & Day 12
Tumor PD: phospho-Akt (Protein Kinase B) Levels (Parts A & B)	Cycle 1 pre-dose & Day 12
Tumor PD: phospho-MAPK (mitogen-activated protein kinase) Levels (Parts A & B)	Cycle 1 pre-dose & Day 12
Bone PD: Cross-Linked N-telopeptides of Type I collagen (NTx) Levels (Parts A & B)	Baseline, Cycle 1 Day 8, & Cycle 3 Day 1