A Study of MK-8033 in Patients With Advanced Solid Tumors (MK-8033-001)
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|ClinicalTrials.gov Identifier: NCT00559182|
Recruitment Status : Completed
First Posted : November 16, 2007
Last Update Posted : July 20, 2015
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|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||47 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
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
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.
- Safety and tolerability of MK-8033 based on drug-related dose limiting toxicity. [ Time Frame: for the entire duration of study (27 months) ]
- Recommended Phase II Dose (RP2D) based on safety, tumor pharmacodynamics, and pharmacokinetics [ Time Frame: for the entire duration of study (27 months) ]
- Plasma area under the curve (AUC) for F2 formulation alone or in combination with omeprazole [ Time Frame: Day 1-21 ]
- 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 ]
- Tumor Pharmacodynamics (PD): phospho-c-Met (MET or MNNG HOS Transforming gene) Levels (Parts A & B) [ Time Frame: Cycle 1 pre-dose & Day 12 ]
- Tumor PD: phospho-Akt (Protein Kinase B) Levels (Parts A & B) [ Time Frame: Cycle 1 pre-dose & Day 12 ]
- Tumor PD: phospho-MAPK (mitogen-activated protein kinase) Levels (Parts A & B) [ Time Frame: Cycle 1 pre-dose & Day 12 ]
- 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 ]
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 ClinicalTrials.gov identifier (NCT number): NCT00559182
|Study Director:||Medical Monitor||Merck Sharp & Dohme Corp.|