Advanced CancerPhase 1NCT00559182
A Study of MK-8033 in Patients With Advanced Solid Tumors (MK-8033-001)
A Phase 1 study testing Comparator: MK-8033 and Comparator: MK-8033 +/- omeprazole in people with Advanced Cancer, run by Merck Sharp & Dohme LLC.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Cancer
- What is being tested?
- Comparator: MK-8033 and Comparator: MK-8033 +/- omeprazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- No sites listed yet
- Study dates
- 5 Dec 2007to 9 Jul 2010
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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)
About this study
Official title: A Phase I Dose Escalation Study of MK-8033 in Patients With Advanced Solid Tumors
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
- Being tested
- Comparator: MK-8033, Comparator: MK-8033 +/- omeprazole
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Comparator: MK-8033Drug
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.
Comparator: MK-8033 +/- omeprazoleDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Parts A and B: MK-8033 | Experimental | Dose Escalation Study Receives: Drug: Comparator: MK-8033 |
| Part C: MK-8033 +/- omeprazole | Experimental | Crossover Study Receives: Drug: Comparator: MK-8033 +/- omeprazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of MK-8033 based on drug-related dose limiting toxicity.
Measured: for the entire duration of study (27 months)
Recommended Phase II Dose (RP2D) based on safety, tumor pharmacodynamics, and pharmacokinetics
Measured: for the entire duration of study (27 months)
Plasma area under the curve (AUC) for F2 formulation alone or in combination with omeprazole
Measured: Day 1-21
Safety and tolerability of MK-8033 F2 formulation alone or in combination with omeprazole based on incidence of adverse experiences
Measured: Day 1-21
Tumor Pharmacodynamics (PD): phospho-c-Met (MET or MNNG HOS Transforming gene) Levels (Parts A & B)
Measured: Cycle 1 pre-dose & Day 12
Tumor PD: phospho-Akt (Protein Kinase B) Levels (Parts A & B)
Measured: Cycle 1 pre-dose & Day 12
Tumor PD: phospho-MAPK (mitogen-activated protein kinase) Levels (Parts A & B)
Measured: Cycle 1 pre-dose & Day 12
Bone PD: Cross-Linked N-telopeptides of Type I collagen (NTx) Levels (Parts A & B)
Measured: Baseline, Cycle 1 Day 8, & Cycle 3 Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2007 (estimated)
- Study start5 Dec 2007
- Primary completion10 Jun 2010
- Study completion9 Jul 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced CancerStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00559182
- Sponsor's protocol ID
- 8033-001
- Other IDs
- 2007_590
- Status last verified
- Jul 2022
- First submitted
- 14 Nov 2007
- Last updated
- 26 Jul 2022
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 29376210
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Dose Escalation Study of MK-8033 in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT00559182
- Acronym / sponsor ID
- 8033-001
- Conditions
- Advanced Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 5 Dec 2007 (actual)
- Primary completion
- 10 Jun 2010 (actual)
- Study completion
- 9 Jul 2010 (actual)
- First posted
- 16 Nov 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Parts A and B: MK-8033 | Experimental | Drug: Comparator: MK-8033Dose Escalation Study |
| Part C: MK-8033 +/- omeprazole | Experimental | Drug: Comparator: MK-8033 +/- omeprazoleCrossover Study |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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)
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Comparator: MK-8033MK-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. | Drug | Parts A and B: MK-8033 |
| Comparator: MK-8033 +/- omeprazolePart 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. | Drug | Part C: MK-8033 +/- omeprazole |
Primary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2022.
- Results publication: PubMed 29376210Keedy 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Monitor study director
Merck Sharp & Dohme LLC
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Comparator: MK-8033 and Comparator: MK-8033 +/- omeprazole in people with Advanced Cancer, run by Merck Sharp & Dohme LLC.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability of MK-8033 based on drug-related dose limiting toxicity. (time frame: for the entire duration of study (27 months)). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00559182, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jul 2022.