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

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: July 30, 2014
Last verified: July 2014
  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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: July 30, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on August 28, 2014