A Study of MK-8033 in Patients With Advanced Solid Tumors (MK-8033-001 AM5)(COMPLETED)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00559182
First received: November 14, 2007
Last updated: August 16, 2013
Last verified: August 2013
  Purpose

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 Intervention Phase
Advanced Cancer
Drug: Comparator: MK-8033
Drug: Comparator: MK-8033 +/- omeprazole
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Dose Escalation Study of MK-8033 in Patients With Advanced Solid Tumors

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Safety and tolerability of MK-8033 based on drug-related dose limiting toxicity. [ Time Frame: for the entire duration of study (27 months) ] [ Designated as safety issue: Yes ]
  • Recommended Phase II Dose (RP2D) based on safety, tumor pharmacodynamics, and pharmacokinetics [ Time Frame: for the entire duration of study (27 months) ] [ Designated as safety issue: Yes ]
  • Plasma area under the curve (AUC) for F2 formulation alone or in combination with omeprazole [ Time Frame: Day 1-21 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Tumor Pharmacodynamics (PD): phospho-c-Met (MET or MNNG HOS Transforming gene) Levels (Parts A & B) [ Time Frame: Cycle 1 pre-dose & Day 12 ] [ Designated as safety issue: No ]
  • Tumor PD: phospho-Akt (Protein Kinase B) Levels (Parts A & B) [ Time Frame: Cycle 1 pre-dose & Day 12 ] [ Designated as safety issue: No ]
  • Tumor PD: phospho-MAPK (mitogen-activated protein kinase) Levels (Parts A & B) [ Time Frame: Cycle 1 pre-dose & Day 12 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 47
Study Start Date: December 2007
Study Completion Date: July 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.


  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00559182

Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Monitor Merck Sharp & Dohme Corp.
  More Information

No publications provided

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00559182     History of Changes
Other Study ID Numbers: 8033-001, 2007_590
Study First Received: November 14, 2007
Last Updated: August 16, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Omeprazole
Anti-Ulcer Agents
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 16, 2014