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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00559182
Recruitment Status : Completed
First Posted : November 16, 2007
Last Update Posted : July 20, 2015
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

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.

Condition or disease Intervention/treatment Phase
Advanced Cancer Drug: Comparator: MK-8033 Drug: Comparator: MK-8033 +/- omeprazole Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 47 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Dose Escalation Study of MK-8033 in Patients With Advanced Solid Tumors
Study Start Date : December 2007
Actual Primary Completion Date : June 2010
Actual Study Completion Date : July 2010

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Parts A and B: MK-8033
Dose Escalation Study
Drug: Comparator: MK-8033

MK-8033 will be administered as an oral formulation in sequentially rising dose levels starting at 50 mg and continuing at 100% dose increments until dose level 4 (800 mg total daily dose). Dose levels 5 to 11 will be escalated at ~40% dose increments until 3000mg (total daily dose). The daily dose of MK-8033 will be divided into two equal doses. MK-8033 will be administered in a first cycle of 14 days (continuous drug administration from Day 1 through Day 14), followed by a 1 week drug holiday (Cycle 1, Day 15 through Day 21). Subsequent cycles of MK-8033 will be administered for 14 days (Cycles 2 to 4) and 28 days (Cycle 5 and beyond).

Enrollment in Parts A and B has been completed.

Experimental: Part C: MK-8033 +/- omeprazole
Crossover Study
Drug: Comparator: MK-8033 +/- omeprazole

Part C will occur at only one of the investigational sites.

In Cycle 1, patients will be randomized to one of two treatment sequences, A/B or B/A, over two treatment periods. Treatment A: 770 mg MK-8033 twice daily with co-administration of 20 mg omeprazole once daily. Treatment B: 770 mg MK-8033 twice daily. After Cycle 1 is complete, patients may continue to receive MK-8033 until disease progression or unacceptable toxicity.

Enrollment for Part C has been suspended.

Primary Outcome Measures :
  1. Safety and tolerability of MK-8033 based on drug-related dose limiting toxicity. [ Time Frame: for the entire duration of study (27 months) ]
  2. Recommended Phase II Dose (RP2D) based on safety, tumor pharmacodynamics, and pharmacokinetics [ Time Frame: for the entire duration of study (27 months) ]
  3. Plasma area under the curve (AUC) for F2 formulation alone or in combination with omeprazole [ Time Frame: Day 1-21 ]
  4. 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 ]
  5. Tumor Pharmacodynamics (PD): phospho-c-Met (MET or MNNG HOS Transforming gene) Levels (Parts A & B) [ Time Frame: Cycle 1 pre-dose & Day 12 ]
  6. Tumor PD: phospho-Akt (Protein Kinase B) Levels (Parts A & B) [ Time Frame: Cycle 1 pre-dose & Day 12 ]
  7. Tumor PD: phospho-MAPK (mitogen-activated protein kinase) Levels (Parts A & B) [ Time Frame: Cycle 1 pre-dose & Day 12 ]
  8. 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 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00559182

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
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Study Director: Medical Monitor Merck Sharp & Dohme Corp.
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Responsible Party: Merck Sharp & Dohme Corp. Identifier: NCT00559182    
Other Study ID Numbers: 8033-001
First Posted: November 16, 2007    Key Record Dates
Last Update Posted: July 20, 2015
Last Verified: July 2015
Additional relevant MeSH terms:
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Anti-Ulcer Agents
Gastrointestinal Agents
Proton Pump Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action