A Study of MK-8033 in Patients With Advanced Solid Tumors (MK-8033-001 AM5)(COMPLETED)
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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 |
- 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 |
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 More Information
No publications provided
| Responsible Party: | Merck |
| ClinicalTrials.gov Identifier: | NCT00559182 History of Changes |
| Other Study ID Numbers: | 8033-001, 2007_590 |
| Study First Received: | November 14, 2007 |
| Last Updated: | May 7, 2012 |
| 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 May 16, 2013