Locally Advanced TumorsPhase 1NCT00670488

Dose Escalation Study With MK-2206 in Patients With Locally Advanced or Metastatic Solid Tumors (MK-2206-002)

A Phase 1 study testing MK-2206 in people with Locally Advanced Tumors and Metastatic Solid Tumors, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The primary purpose of this study is to investigate the Dose Limiting Toxicities (DLTs), pharmacokinetics (PK), and pharmacodynamics (PD) of MK-2206 administered orally to participants with advanced solid tumors. The preliminary efficacy of MK-2206 will also be investigated. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Locally Advanced Tumors, Metastatic Solid Tumors, Cancer
What is being tested?: MK-2206
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 104 participants
Where: No sites listed yet
Study dates: 15 Apr 2008to 11 Jul 2011
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

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

Participant must have confirmed locally advanced or metastatic solid tumors that have failed to respond to standard therapy, have gotten worse or have come back after existing therapy
Has normal organ function; is no greater than 2 on the ECOG Performance Scale
Has a negative blood or urine pregnancy test within 72 hours of receiving the first dose of study drug if participant is female
Is able to swallow capsules and has no surgical or bodily condition that will prevent the patient from swallowing and absorbing oral medications on an ongoing basis

Who cannot join

Participant has had chemotherapy, radiotherapy, biological therapy or surgery within 4 weeks of starting the study and has not recovered from adverse events caused by the treatment
Is currently participating or has participated in a study with an investigational compound or device within 30 days
Has a primary central nervous system tumor
Has a history or current evidence of heart disease, slow heart rate or untreated high blood pressure
Is a known diabetic who is taking insulin or oral antidiabetic therapy
Is pregnant or breastfeeding or planning to become pregnant during the study

Show all 9Show fewer

Is HIV-positive
Has known history of Hepatitis B or C or active Hepatitis A
Is receiving treatment with oral corticosteroids

About this study

Official title: A Phase I Dose Escalation Study of Oral MK-2206 in Patients With Locally Advanced or Metastatic Solid Tumors

Conditions: Locally Advanced Tumors, Metastatic Solid Tumors, Cancer, Neoplasms
Being tested: MK-2206
Medical subject headings: Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MK-2206Drug
MK-2206 administered as an oral formulation in rising dose levels on a QOD schedule (30 mg, 60 mg, 75 mg, and 90 mg) or QW schedule (90 mg, 135 mg, 200 mg, 250 mg, and 300 mg) in repeating 4 week cycles, depending upon allocation.

Study groups in NCT00670488
Study group	Role	What they receive
MK-2206 30 mg QOD	Experimental	Participants receive 30 mg oral MK-2206 every other day (QOD) in repeating 4-week treatment cycles. Receives: Drug: MK-2206
MK-2206 60 mg QOD	Experimental	Participants receive 60 mg oral MK-2206 QOD in repeating 4-week treatment cycles. Receives: Drug: MK-2206
MK-2206 75 mg QOD	Experimental	Participants receive 75 mg oral MK-2206 QOD in repeating 4-week treatment cycles. Receives: Drug: MK-2206
MK-2206 90 mg QOD	Experimental	Participants receive 90 mg oral MK-2206 QOD in repeating 4-week treatment cycles. Receives: Drug: MK-2206
MK-2206 90 mg QW	Experimental	Participants receive 90 mg oral MK-2206 every week (QW) in repeating 4-week treatment cycles. Receives: Drug: MK-2206
MK-2206 135 mg QW	Experimental	Participants receive 135 mg oral MK-2206 QW in repeating 4-week treatment cycles. Receives: Drug: MK-2206
MK-2206 200 mg QW	Experimental	Participants receive 200 mg oral MK-2206 QW in repeating 4-week treatment cycles. Receives: Drug: MK-2206
MK-2206 300 mg QW	Experimental	Participants receive 300 mg oral MK-2206 QW in repeating 4-week treatment cycles. Receives: Drug: MK-2206
MK-2206 250 mg QW	Experimental	Participants receive 250 mg oral MK-2206 QW in repeating 4-week treatment cycles. Receives: Drug: MK-2206
MK-2206 150 mg QW	Experimental	Participants receive 150 mg oral MK-2206 QW in repeating 4-week treatment cycles. Receives: Drug: MK-2206

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Dose Limiting Toxicities (DLTs)
DLT was any drug-related AE, regardless of grade, leading to a dose modification of MK-2206. Dose-limiting hematologic and nonhematologic toxicities were defined differently and were based on events occurring during the first cycle of study drug administration. Hematologic DLT defined as any Grade (Gr) 4 or greater hematologic toxicity except neutropenia described as follows: Neutropenia that was Gr 4 lasting for ≥7 days, or Gr 3/Gr 4 with fever >38.5°C and/or infection requiring antibiotic or anti-fungal treatment considered DLT. Gr 4 thrombocytopenia (≤25.0 x 10^9/L) was also considered DLT. Non-hematologic DLTs were defined as any Gr 3, 4, or 5 nonhematologic toxicity, with the specific exceptions of: Gr 3 nausea, vomiting, diarrhea, or dehydration occurring with inadequate supportive care and lasting <48 hours; alopecia; inadequately treated hypersensitivity reactions; and Gr 3 elevated transaminases of ≤1 week in duration. A participant could have more than one DLT.
Measured: Day 1 to Day 28 (Cycle 1)
Number of Participants With One or More Adverse Events (AE)
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which was temporally associated with the use of the SPONSOR's product, was also an AE. The number of participants that experienced one or more AEs was reported for each dose level group.
Measured: Up to 269 days
Area Under the Concentration-time Curve of MK-2206 From Time 0 to 48 Hours (AUC0-48hr) in Participants Receiving Multiple QOD Dosing
Blood samples were collected for PK analyses during the first cycle of therapy. Samples were centrifuged, plasma was withdrawn and plasma concentrations were analyzed by high performance liquid chromatography with tandem mass spectroscopy. AUC 0-48hr was calculated for Day 1 and the last day of treatment in Cycle 1 (Day 27) and reported for all dose levels receiving MK-2206 orally QOD (30, 60, 75, and 90 mg QOD).
Measured: Days 1 and 27: predose and 0.5, 1, 2, 3, 4, 6, 10, 24, and 48 hours after MK-2206 dosing
Maximum Concentration (Cmax) of MK-2206 in Participants Receiving Multiple QOD Dosing
Blood samples were collected for PK analyses during the first cycle of therapy. Samples were centrifuged, plasma was withdrawn and plasma concentrations were analyzed by high performance liquid chromatography with tandem mass spectroscopy. Cmax was calculated for Day 1 and the last day of treatment in Cycle 1 (Day 27) and reported for all dose levels receiving MK-2206 orally QOD (30, 60, 75, and 90 mg QOD).
Measured: Days 1 and 27: predose and 0.5, 1, 2, 3, 4, 6, 10, 24, and 48 hours after MK-2206 dosing
Concentration of MK-2206 After 48 Hours (C48hr) in Participants Receiving Multiple QOD Dosing
Blood samples were collected for PK analyses during the first cycle of therapy. Samples were centrifuged, plasma was withdrawn and plasma concentrations were analyzed by high performance liquid chromatography with tandem mass spectroscopy. C48hr was calculated for Day 1 and the last day of treatment in Cycle 1 (Day 27) and reported for all dose levels receiving MK-2206 orally QOD (30, 60, 75, and 90 mg QOD).
Measured: Days 1 and 27: predose and 48 hours after MK-2206 dosing.
Time to Maximum Concentration (Tmax) of MK-2206 in Participants Receiving Multiple QOD Dosing
Blood samples were collected for PK analyses during the first cycle of therapy. Samples were centrifuged, plasma was withdrawn and plasma concentrations were analyzed by high performance liquid chromatography with tandem mass spectroscopy. Tmax was calculated for Day 1 and the last day of treatment in Cycle 1 and reported for all dose levels receiving MK-2206 orally QOD (30, 60, 75, and 90 mg QOD).
Measured: Days 1 and 27: predose and 0.5, 1, 2, 3, 4, 6, 10, 24, and 48 hours after MK-2206 dosing
Apparent Terminal Half-life (t½) of MK-2206 in Participants Receiving Multiple QOD Dosing
Blood samples were collected for PK analyses on Day 27 of the first cycle of therapy. Samples were centrifuged, plasma was withdrawn and plasma concentrations were analyzed by high performance liquid chromatography with tandem mass spectroscopy. t½ (Harmonic mean ± pseudo SD) was calculated and reported for all dose levels receiving MK-2206 orally QOD (30, 60, 75, and 90 mg QOD).
Measured: Day 27: predose and 0.5, 1, 2, 3, 4, 6, 10, 24, and 48 hours after MK-2206 dosing.
AUC0-168hr in Participants Receiving Multiple QW Dosing
Blood samples were collected for PK analyses during the first cycle of therapy. Samples were centrifuged, plasma was withdrawn and plasma concentrations were analyzed by high performance liquid chromatography with tandem mass spectroscopy. AUC 0-168 was calculated for Day 1 and the last day of treatment in Cycle 1 and reported for all dose levels receiving MK-2206 orally QW (90, 135, 200, 300, 250, and 150 mg QW).
Measured: Days 1 and 22: predose and 2, 4, 6, 10, 24, 48, 96 hours, and 168 hours after MK-2206 dosing
Cmax of MK-2206 in Participants Receiving Multiple QW Dosing
Blood samples were collected for PK analyses during the first cycle of therapy. Samples were centrifuged, plasma was withdrawn and plasma concentrations were analyzed by high performance liquid chromatography with tandem mass spectroscopy. Cmax was calculated for Day 1 and the last day of treatment in Cycle 1 and reported for all dose levels receiving MK-2206 orally QW (90, 135, 200, 300, 250, and 150 mg QW).
Measured: Days 1 and 22: predose and 2, 4, 6, 10, 24, 48, 96 hours, and 168 hours after MK-2206 dosing
C48hr of MK-2206 in Participants Receiving Multiple QW Dosing
Blood samples were collected for PK analyses during the first cycle of therapy. Samples were centrifuged, plasma was withdrawn and plasma concentrations were analyzed by high performance liquid chromatography with tandem mass spectroscopy. C48hr was calculated for Day 1 and the last day of treatment in Cycle 1 and reported for all dose levels receiving MK-2206 orally QW (90, 135, 200, 300, 250, and 150 mg QW).
Measured: Days 1 and 22: predose and 48 hours after MK-2206 dosing
Tmax of MK-2206 in Participants Receiving Multiple QW Dosing
Blood samples were collected for PK analyses during the first cycle of therapy. Samples were centrifuged, plasma was withdrawn and plasma concentrations were analyzed by high performance liquid chromatography with tandem mass spectroscopy. Tmax was calculated for Day 1 and the last day of treatment in Cycle 1 and reported for all dose levels receiving MK-2206 orally QW (90, 135, 200, 300, 250, and 150 mg QW).
Measured: Days 1 and 22: predose and 2, 4, 6, 10, 24, 48, 96 hours, and 168 hours after MK-2206 dosing
t½ of MK-2206 in Participants Receiving Multiple QW Dosing
Blood samples were collected for PK analyses during the first cycle of therapy. Samples were centrifuged, plasma was withdrawn and plasma concentrations were analyzed by high performance liquid chromatography with tandem mass spectroscopy. t½ (Harmonic mean ± pseudo SD) was calculated for the last day of treatment in Cycle 1 and reported for all dose levels receiving MK-2206 orally QW (90, 135, 200, 300, 250, and 150 mg QW).
Measured: Day 22: predose and 2, 4, 6, 10, 24, 48, 96 hours, and 168 hours after MK-2206 dosing

Secondary outcomes (2)

Phosphorylated Protein Kinase B (pAkt) Level on Cycle 1 Day 15 (C1D15) After Treatment With MK-2206 at the Maximum Tolerated Dose (MTD)
To determine the inhibition of pAkt by MK-2206 in participants treated at the MTD, levels of Akt phosphorylated at the serine 473 residue (pAkt Ser473 Akt) were measured in snap-frozen tumors collected at baseline and Day 15 of Cycle 1 using a MesoScale enzyme-linked immunosorbent assay (ELISA). Per protocol, pAkt levels were determined only for the MK-2206 MTD (60 mg QOD) group.
Measured: Baseline, Cycle 1 Day 15
Number of Participants With Confirmed Response as Per Response Evaluation Criteria in Solid Tumors (RECIST)
Overall tumor response was assessed during the study by diagnostic anatomic imaging using RECIST. The number of participants with a confirmed Complete Response (CR: Disappearance of all target lesions) as per RECIST was reported for each dose level group.
Measured: From Cycle 1 Day 1 through the End of Study Visit (up to 6 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

15 Apr 200811 Jul 2011

First posted1 May 2008 (estimated)
Study start15 Apr 2008
Primary completion11 Jul 2011
Study completion11 Jul 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Locally Advanced TumorsStudies 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: Parallel groups
Masking: None (open label)
Enrolment: 104 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00670488
Sponsor's protocol ID: 2206-002
Other IDs: 2008_513, MK-2206-002
Status last verified: Jan 2019
First submitted: 29 Apr 2008
Last updated: 1 Apr 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

Yap TA, Yan L, Patnaik A, Fearen I, Olmos D, Papadopoulos K, Baird RD, Delgado L, Taylor A, Lupinacci L, Riisnaes R, Pope LL, Heaton SP, Thomas G, Garrett MD, Sullivan DM, de Bono JS, Tolcher AW. First-in-man clinical trial of the oral pan-AKT inhibitor MK-2206 in patients with advanced solid tumors. J Clin Oncol. 2011 Dec 10;29(35):4688-95. doi: 10.1200/JCO.2011.35.5263. Epub 2011 Oct 24.
PubMed 22025163
Yap TA, Yan L, Patnaik A, Tunariu N, Biondo A, Fearen I, Papadopoulos KP, Olmos D, Baird R, Delgado L, Tetteh E, Beckman RA, Lupinacci L, Riisnaes R, Decordova S, Heaton SP, Swales K, deSouza NM, Leach MO, Garrett MD, Sullivan DM, de Bono JS, Tolcher AW. Interrogating two schedules of the AKT inhibitor MK-2206 in patients with advanced solid tumors incorporating novel pharmacodynamic and functional imaging biomarkers. Clin Cancer Res. 2014 Nov 15;20(22):5672-85. doi: 10.1158/1078-0432.CCR-14-0868. Epub 2014 Sep 19.
PubMed 25239610

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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Study at a glance

From the registry record, last updated by the sponsor on 1 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I Dose Escalation Study of Oral MK-2206 in Patients With Locally Advanced or Metastatic Solid Tumors
ClinicalTrials.gov ID: NCT00670488
Acronym / sponsor ID: 2206-002
Conditions: Locally Advanced Tumors, Metastatic Solid Tumors, Cancer, Neoplasms
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 104 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 15 Apr 2008 (actual)
Primary completion: 11 Jul 2011 (actual)
Study completion: 11 Jul 2011 (actual)
First posted: 1 May 2008 (estimated)
Results: Posted 1 Apr 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 10

Arm	Type	Receives
MK-2206 30 mg QOD	Experimental	Drug: MK-2206Participants receive 30 mg oral MK-2206 every other day (QOD) in repeating 4-week treatment cycles.
MK-2206 60 mg QOD	Experimental	Drug: MK-2206Participants receive 60 mg oral MK-2206 QOD in repeating 4-week treatment cycles.
MK-2206 75 mg QOD	Experimental	Drug: MK-2206Participants receive 75 mg oral MK-2206 QOD in repeating 4-week treatment cycles.
MK-2206 90 mg QOD	Experimental	Drug: MK-2206Participants receive 90 mg oral MK-2206 QOD in repeating 4-week treatment cycles.
MK-2206 90 mg QW	Experimental	Drug: MK-2206Participants receive 90 mg oral MK-2206 every week (QW) in repeating 4-week treatment cycles.
MK-2206 135 mg QW	Experimental	Drug: MK-2206Participants receive 135 mg oral MK-2206 QW in repeating 4-week treatment cycles.
MK-2206 200 mg QW	Experimental	Drug: MK-2206Participants receive 200 mg oral MK-2206 QW in repeating 4-week treatment cycles.
MK-2206 300 mg QW	Experimental	Drug: MK-2206Participants receive 300 mg oral MK-2206 QW in repeating 4-week treatment cycles.
MK-2206 250 mg QW	Experimental	Drug: MK-2206Participants receive 250 mg oral MK-2206 QW in repeating 4-week treatment cycles.
MK-2206 150 mg QW	Experimental	Drug: MK-2206Participants receive 150 mg oral MK-2206 QW in repeating 4-week treatment cycles.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Participant must have confirmed locally advanced or metastatic solid tumors that have failed to respond to standard therapy, have gotten worse or have come back after existing therapy
Has normal organ function; is no greater than 2 on the ECOG Performance Scale
Has a negative blood or urine pregnancy test within 72 hours of receiving the first dose of study drug if participant is female
Is able to swallow capsules and has no surgical or bodily condition that will prevent the patient from swallowing and absorbing oral medications on an ongoing basis

Key exclusion criteria (9 listed)

Participant has had chemotherapy, radiotherapy, biological therapy or surgery within 4 weeks of starting the study and has not recovered from adverse events caused by the treatment
Is currently participating or has participated in a study with an investigational compound or device within 30 days
Has a primary central nervous system tumor
Has a history or current evidence of heart disease, slow heart rate or untreated high blood pressure
Is a known diabetic who is taking insulin or oral antidiabetic therapy

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
MK-2206MK-2206 administered as an oral formulation in rising dose levels on a QOD schedule (30 mg, 60 mg, 75 mg, and 90 mg) or QW schedule (90 mg, 135 mg, 200 mg, 250 mg, and 300 mg) in repeating 4 week cycles, depending upon allocation.	Drug	MK-2206 135 mg QW, MK-2206 150 mg QW, MK-2206 200 mg QW, MK-2206 250 mg QW, MK-2206 30 mg QOD, MK-2206 300 mg QW, MK-2206 60 mg QOD, MK-2206 75 mg QOD, MK-2206 90 mg QOD, MK-2206 90 mg QW

Primary outcome

Number of Participants With Dose Limiting Toxicities (DLTs)
Time frame: Day 1 to Day 28 (Cycle 1)
DLT was any drug-related AE, regardless of grade, leading to a dose modification of MK-2206. Dose-limiting hematologic and nonhematologic toxicities were defined differently and were based on events occurring during the first cycle of study drug administration. Hematologic DLT defined as any Grade (Gr) 4 or greater hematologic toxicity except neutropenia described as follows: Neutropenia that was Gr 4 lasting for ≥7 days, or Gr 3/Gr 4 with fever >38.5°C and/or infection requiring antibiotic or anti-fungal treatment considered DLT. Gr 4 thrombocytopenia (≤25.0 x 10^9/L) was also considered DLT. Non-hematologic DLTs were defined as any Gr 3, 4, or 5 nonhematologic toxicity, with the specific exceptions of: Gr 3 nausea, vomiting, diarrhea, or dehydration occurring with inadequate supportive care and lasting <48 hours; alopecia; inadequately treated hypersensitivity reactions; and Gr 3 elevated transaminases of ≤1 week in duration. A participant could have more than one DLT.
Number of Participants With One or More Adverse Events (AE)
Time frame: Up to 269 days
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which was temporally associated with the use of the SPONSOR's product, was also an AE. The number of participants that experienced one or more AEs was reported for each dose level group.
Area Under the Concentration-time Curve of MK-2206 From Time 0 to 48 Hours (AUC0-48hr) in Participants Receiving Multiple QOD Dosing
Time frame: Days 1 and 27: predose and 0.5, 1, 2, 3, 4, 6, 10, 24, and 48 hours after MK-2206 dosing
Blood samples were collected for PK analyses during the first cycle of therapy. Samples were centrifuged, plasma was withdrawn and plasma concentrations were analyzed by high performance liquid chromatography with tandem mass spectroscopy. AUC 0-48hr was calculated for Day 1 and the last day of treatment in Cycle 1 (Day 27) and reported for all dose levels receiving MK-2206 orally QOD (30, 60, 75, and 90 mg QOD).
Maximum Concentration (Cmax) of MK-2206 in Participants Receiving Multiple QOD Dosing
Time frame: Days 1 and 27: predose and 0.5, 1, 2, 3, 4, 6, 10, 24, and 48 hours after MK-2206 dosing
Blood samples were collected for PK analyses during the first cycle of therapy. Samples were centrifuged, plasma was withdrawn and plasma concentrations were analyzed by high performance liquid chromatography with tandem mass spectroscopy. Cmax was calculated for Day 1 and the last day of treatment in Cycle 1 (Day 27) and reported for all dose levels receiving MK-2206 orally QOD (30, 60, 75, and 90 mg QOD).
Concentration of MK-2206 After 48 Hours (C48hr) in Participants Receiving Multiple QOD Dosing
Time frame: Days 1 and 27: predose and 48 hours after MK-2206 dosing.
Blood samples were collected for PK analyses during the first cycle of therapy. Samples were centrifuged, plasma was withdrawn and plasma concentrations were analyzed by high performance liquid chromatography with tandem mass spectroscopy. C48hr was calculated for Day 1 and the last day of treatment in Cycle 1 (Day 27) and reported for all dose levels receiving MK-2206 orally QOD (30, 60, 75, and 90 mg QOD).
Time to Maximum Concentration (Tmax) of MK-2206 in Participants Receiving Multiple QOD Dosing
Time frame: Days 1 and 27: predose and 0.5, 1, 2, 3, 4, 6, 10, 24, and 48 hours after MK-2206 dosing
Blood samples were collected for PK analyses during the first cycle of therapy. Samples were centrifuged, plasma was withdrawn and plasma concentrations were analyzed by high performance liquid chromatography with tandem mass spectroscopy. Tmax was calculated for Day 1 and the last day of treatment in Cycle 1 and reported for all dose levels receiving MK-2206 orally QOD (30, 60, 75, and 90 mg QOD).
Apparent Terminal Half-life (t½) of MK-2206 in Participants Receiving Multiple QOD Dosing
Time frame: Day 27: predose and 0.5, 1, 2, 3, 4, 6, 10, 24, and 48 hours after MK-2206 dosing.
Blood samples were collected for PK analyses on Day 27 of the first cycle of therapy. Samples were centrifuged, plasma was withdrawn and plasma concentrations were analyzed by high performance liquid chromatography with tandem mass spectroscopy. t½ (Harmonic mean ± pseudo SD) was calculated and reported for all dose levels receiving MK-2206 orally QOD (30, 60, 75, and 90 mg QOD).
AUC0-168hr in Participants Receiving Multiple QW Dosing
Time frame: Days 1 and 22: predose and 2, 4, 6, 10, 24, 48, 96 hours, and 168 hours after MK-2206 dosing
Blood samples were collected for PK analyses during the first cycle of therapy. Samples were centrifuged, plasma was withdrawn and plasma concentrations were analyzed by high performance liquid chromatography with tandem mass spectroscopy. AUC 0-168 was calculated for Day 1 and the last day of treatment in Cycle 1 and reported for all dose levels receiving MK-2206 orally QW (90, 135, 200, 300, 250, and 150 mg QW).
Cmax of MK-2206 in Participants Receiving Multiple QW Dosing
Time frame: Days 1 and 22: predose and 2, 4, 6, 10, 24, 48, 96 hours, and 168 hours after MK-2206 dosing
Blood samples were collected for PK analyses during the first cycle of therapy. Samples were centrifuged, plasma was withdrawn and plasma concentrations were analyzed by high performance liquid chromatography with tandem mass spectroscopy. Cmax was calculated for Day 1 and the last day of treatment in Cycle 1 and reported for all dose levels receiving MK-2206 orally QW (90, 135, 200, 300, 250, and 150 mg QW).
C48hr of MK-2206 in Participants Receiving Multiple QW Dosing
Time frame: Days 1 and 22: predose and 48 hours after MK-2206 dosing
Blood samples were collected for PK analyses during the first cycle of therapy. Samples were centrifuged, plasma was withdrawn and plasma concentrations were analyzed by high performance liquid chromatography with tandem mass spectroscopy. C48hr was calculated for Day 1 and the last day of treatment in Cycle 1 and reported for all dose levels receiving MK-2206 orally QW (90, 135, 200, 300, 250, and 150 mg QW).
Tmax of MK-2206 in Participants Receiving Multiple QW Dosing
Time frame: Days 1 and 22: predose and 2, 4, 6, 10, 24, 48, 96 hours, and 168 hours after MK-2206 dosing
Blood samples were collected for PK analyses during the first cycle of therapy. Samples were centrifuged, plasma was withdrawn and plasma concentrations were analyzed by high performance liquid chromatography with tandem mass spectroscopy. Tmax was calculated for Day 1 and the last day of treatment in Cycle 1 and reported for all dose levels receiving MK-2206 orally QW (90, 135, 200, 300, 250, and 150 mg QW).
t½ of MK-2206 in Participants Receiving Multiple QW Dosing
Time frame: Day 22: predose and 2, 4, 6, 10, 24, 48, 96 hours, and 168 hours after MK-2206 dosing
Blood samples were collected for PK analyses during the first cycle of therapy. Samples were centrifuged, plasma was withdrawn and plasma concentrations were analyzed by high performance liquid chromatography with tandem mass spectroscopy. t½ (Harmonic mean ± pseudo SD) was calculated for the last day of treatment in Cycle 1 and reported for all dose levels receiving MK-2206 orally QW (90, 135, 200, 300, 250, and 150 mg QW).

2 secondary outcomes

Phosphorylated Protein Kinase B (pAkt) Level on Cycle 1 Day 15 (C1D15) After Treatment With MK-2206 at the Maximum Tolerated Dose (MTD)
Time frame: Baseline, Cycle 1 Day 15
Number of Participants With Confirmed Response as Per Response Evaluation Criteria in Solid Tumors (RECIST)
Time frame: From Cycle 1 Day 1 through the End of Study Visit (up to 6 months)

Results and safety

Results posted to the registry on 1 Apr 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
MK-2206 30 mg QOD	3	0
MK-2206 60 mg QOD	58	0
MK-2206 75 mg QOD	3	0
MK-2206 90 mg QOD	7	0
MK-2206 90 mg QW	3	0
MK-2206 135 mg QW	5	0
MK-2206 200 mg QW	17	0
MK-2206 300 mg QW	3	0
MK-2206 250 mg QW	3	0
MK-2206 150 mg QW	2	0

Primary outcome: Number of Participants With Dose Limiting Toxicities (DLTs)

Time frame: Day 1 to Day 28 (Cycle 1). Count of participants. Unit: Participants

Measure	MK-2206 60 mg QOD n = 58	MK-2206 75 mg QOD n = 3	MK-2206 90 mg QOD n = 7	MK-2206 200 mg QW n = 17	MK-2206 300 mg QW n = 3	MK-2206 250 mg QW n = 3	MK-2206 150 mg QW n = 2
Hyperglycaemia	1	0	0	0	0	0	0
Rash	5	2	3	3	2	2	1
Rash macular	2	0	0	0	0	0	0
Stomatitis	1	0	0	0	0	0	0
Diarrhoea	0	1	0	0	0	0	0
Pruritis	0	0	1	0	0	0	0
Rash generalized	0	0	1	0	1	0	0
Dermatitis acneiform	0	0	0	1	0	0	0

Population analysed: The All Participants as Treated (APaT) population: All participants who received at least one dose of study treatment.

Primary outcome: Number of Participants With One or More Adverse Events (AE)

Time frame: Up to 269 days. Count of participants. Unit: Participants

Measure	MK-2206 30 mg QOD n = 3	MK-2206 60 mg QOD n = 58	MK-2206 75 mg QOD n = 3	MK-2206 90 mg QOD n = 7	MK-2206 90 mg QW n = 3	MK-2206 135 mg QW n = 5	MK-2206 200 mg QW n = 17	MK-2206 300 mg QW n = 3	MK-2206 250 mg QW n = 3	MK-2206 150 mg QW n = 2
Value	3	58	3	7	3	5	17	3	3	2

Population analysed: APaT population: All participants who received at least one dose of study treatment.

Primary outcome: Area Under the Concentration-time Curve of MK-2206 From Time 0 to 48 Hours (AUC0-48hr) in Participants Receiving Multiple QOD Dosing

Time frame: Days 1 and 27: predose and 0.5, 1, 2, 3, 4, 6, 10, 24, and 48 hours after MK-2206 dosing. Mean (Standard Deviation). Unit: nM•hr

Measure	MK-2206 30 mg QOD n = 3	MK-2206 60 mg QOD n = 58	MK-2206 75 mg QOD n = 3	MK-2206 90 mg QOD n = 7	MK-2206 90 mg QW n = 0	MK-2206 135 mg QW n = 0	MK-2206 200 mg QW n = 0	MK-2206 300 mg QW n = 0	MK-2206 250 mg QW n = 0	MK-2206 150 mg QW n = 0
Day 1	916 (395)	1950 (832)	2110 (782)	3950 (1920)	–	–	–	–	–	–
Last Day (Day 27)	NA (NA)	6160 (2690)	NA (NA)	7970 (5990)	–	–	–	–	–	–

MK-2206 60 mg QOD: AUC0-48hr GMR: 3.26
MK-2206 90 mg QOD: AUC 0-48hr GMR: 3.18

Population analysed: All participants who received MK-2206 orally QOD during Cycle 1 (30, 60, 75, and 90 mg QOD) and had available PK data. Data for the MK-2206 QW dose groups (90, 135, 200, 300, 250, and 150 mg QW) are reported separately.

Primary outcome: Maximum Concentration (Cmax) of MK-2206 in Participants Receiving Multiple QOD Dosing

Time frame: Days 1 and 27: predose and 0.5, 1, 2, 3, 4, 6, 10, 24, and 48 hours after MK-2206 dosing. Mean (Standard Deviation). Unit: nM

Measure	MK-2206 30 mg QOD n = 3	MK-2206 60 mg QOD n = 58	MK-2206 75 mg QOD n = 3	MK-2206 90 mg QOD n = 7	MK-2206 90 mg QW n = 0	MK-2206 135 mg QW n = 0	MK-2206 200 mg QW n = 0	MK-2206 300 mg QW n = 0	MK-2206 250 mg QW n = 0	MK-2206 150 mg QW n = 0
Day 1	33.7 (15.8)	71.6 (36.3)	102 (79.9)	132 (76.5)	–	–	–	–	–	–
Last Day (Day 27)	NA (NA)	176 (77.9)	NA (NA)	232 (148)	–	–	–	–	–	–

MK-2206 60 mg QOD: Cmax GMR: 2.59
MK-2206 90 mg QOD: Cmax GMR: 2.67

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 269 days. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
MK-2206 30 mg QOD	1 of 3 (33.3%)	3 of 3 (100%)	0 of 3
MK-2206 60 mg QOD	21 of 58 (36.2%)	56 of 58 (96.6%)	5 of 58
MK-2206 75 mg QOD	0 of 3 (0%)	3 of 3 (100%)	0 of 3
MK-2206 90 mg QOD	5 of 7 (71.4%)	7 of 7 (100%)	0 of 7
MK-2206 90 mg QW	0 of 3 (0%)	3 of 3 (100%)	0 of 3
MK-2206 135 mg QW	3 of 5 (60%)	4 of 5 (80%)	2 of 5
MK-2206 200 mg QW	8 of 17 (47.1%)	16 of 17 (94.1%)	3 of 17
MK-2206 300 mg QW	2 of 3 (66.7%)	3 of 3 (100%)	0 of 3
MK-2206 250 mg QW	0 of 3 (0%)	3 of 3 (100%)	0 of 3
MK-2206 150 mg QW	2 of 2 (100%)	2 of 2 (100%)	1 of 2

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 22025163Yap TA, Yan L, Patnaik A, Fearen I, Olmos D, Papadopoulos K, Baird RD, Delgado L, Taylor A, Lupinacci L, Riisnaes R, Pope LL, Heaton SP, Thomas G, Garrett MD, Sullivan DM, de Bono JS, Tolcher AW. First-in-man clinical trial of the oral pan-AKT inhibitor MK-2206 in patients with advanced solid tumors. J Clin Oncol. 2011 Dec 10;29(35):4688-95. doi: 10.1200/JCO.2011.35.5263. Epub 2011 Oct 24.
Derived from this study: PubMed 25239610Yap TA, Yan L, Patnaik A, Tunariu N, Biondo A, Fearen I, Papadopoulos KP, Olmos D, Baird R, Delgado L, Tetteh E, Beckman RA, Lupinacci L, Riisnaes R, Decordova S, Heaton SP, Swales K, deSouza NM, Leach MO, Garrett MD, Sullivan DM, de Bono JS, Tolcher AW. Interrogating two schedules of the AKT inhibitor MK-2206 in patients with advanced solid tumors incorporating novel pharmacodynamic and functional imaging biomarkers. Clin Cancer Res. 2014 Nov 15;20(22):5672-85. doi: 10.1158/1078-0432.CCR-14-0868. Epub 2014 Sep 19.
Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

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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 MK-2206 in people with Locally Advanced Tumors and Metastatic Solid Tumors, 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 4 inclusion and 9 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 1 Apr 2019. 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?

Yes. Results are posted in the registry (first posted 1 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Participants With Dose Limiting Toxicities (DLTs) (time frame: Day 1 to Day 28 (Cycle 1)). The study lists 12 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 NCT00670488, which also lists 2 linked publications.

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 1 Apr 2019.