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

NCT ID: NCT00559182

Last Updated: 2022-07-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 47 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-12-05
• Study Completion Date: 2010-07-09

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.

Conditions

Advanced Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Parts A and B: MK-8033

Dose Escalation Study

Group Type: EXPERIMENTAL

Comparator: MK-8033

Intervention Type: DRUG

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.

Part C: MK-8033 +/- omeprazole

Crossover Study

Group Type: EXPERIMENTAL

Comparator: MK-8033 +/- omeprazole

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

Keedy VL, Lenz HJ, Saltz L, Whisenant JG, Berlin JD, Camacho LH. First-in-human phase I dose escalation study of MK-8033 in patients with advanced solid tumors. Invest New Drugs. 2018 Oct;36(5):860-868. doi: 10.1007/s10637-018-0567-z. Epub 2018 Jan 29.

Reference Type: RESULT

PMID: 29376210 (View on PubMed)

Other Identifiers

2007_590

Identifier Type: -

Identifier Source: secondary_id

8033-001

Identifier Type: -

Identifier Source: org_study_id