Locally Advanced, Metastatic Solid TumorsPhase 1NCT00848718

A Phase I Study of MK-2206 in Combination With Standard Chemotherapy in Participants With Locally Advanced or Metastatic Solid Tumors (MK-2206-003)

A Phase 1 study testing MK-2206, docetaxel and erlotinib in people with Locally Advanced, 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 purpose of this study is to compare the safety and tolerability of several dose levels of MK-2206 in combination with chemotherapy and targeted therapy agents in participants with locally advanced or metastatic solid tumors. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Locally Advanced, Metastatic Solid Tumors
What is being tested?: MK-2206, docetaxel and erlotinib
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 77 participants
Where: No sites listed yet
Study dates: 17 Mar 2009to 17 May 2012
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

Participants must have locally advanced or metastatic solid tumors.
Participant is male or female greater than or equal to 18 years of age.
Participant must have a performance status less than or equal to 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
Female participants of childbearing potential has a negative serum or urine pregnancy test within 72 hours prior to receiving the first dose of study medication.
Participants in the MK-2206 + carboplatin/paclitaxel and MK-2206 + docetaxel treatment arms will be limited to no more than 3 prior cytotoxic therapies for metastatic or recurrent diseases.
Participant is able to swallow capsules and has no surgical or anatomical condition that will prevent the Participant from swallowing.

Who cannot join

Participant has had chemotherapy, radiotherapy or biological therapy within 4 weeks.
Participants must be least 4 weeks post-surgery and do not expect major surgery in the study duration.
Participant is currently participating or has participated in a study with an investigational compound or device within 30 days.
Participant has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
Participant with a primary central nervous system tumor.
Participant has known hypersensitivity to the components of study drug.

Show all 19Show fewer

Participant has a history or current evidence of heart disease.
Participant has evidence of clinically significant bradycardia (slow heart rate).
Participant has uncontrolled high blood pressure.
Participant at significant risk for hypokalemia (low potassium levels).
Participant is a known diabetic
Participant has known psychiatric or substance abuse disorders.
Participant is a user of illicit drugs.
Participant is pregnant or breastfeeding.
Participant is Human Immunodeficiency Virus (HIV) positive.
Participant has known history of Hepatitis B or C or active Hepatitis A.
Participant has symptomatic ascites or pleural effusion.
Participant is receiving treatment with oral corticosteroids.
Participant is using a potent cytochrome P(450) 3A4 (CYP3A4) inhibitor or inducer.

About this study

Official title: A Phase I Dose Escalation Study of MK-2206 in Combination With Standard Doses of Selected Chemotherapies or Targeted Agents in Patients With Locally Advanced or Metastatic Solid Tumors

The primary hypotheses are that administration of MK-2206 in combination with either carboplatin + paclitaxel, docetaxel, or erlotinib in participants with locally advanced or metastatic solid tumors will have acceptable tolerability, a dose limiting toxicity (DLT) rate of ≤30%, plasma exposure and pharmacodynamics that exceed target thresholds, and allow for definition of a maximum tolerated dose (MTD) in each of the 3 combinations.

Conditions: Locally Advanced, Metastatic Solid Tumors
Being tested: MK-2206, docetaxel, erlotinib, carboplatin, paclitaxel
Keywords: Tumors, cancer
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 given by mouth (PO) on Days 1, 3, 5, and 7 of each 21-day cycle (30 mg, 45 mg, or 60 mg) OR MK-2206 PO on Day 1 of each 21-day cycle (60 mg, 90 mg, 135 mg, 200 mg , or 250 mg)
docetaxelDrug
Also called Taxotere®
Administered as an IV infusion on Day 1 of each 21-day cycle
erlotinibDrug
Also called Tarceva®
Administered daily (QD) PO in each 21-day cycle
carboplatinDrug
Also called Paraplatin®
Administered as an intravenous (IV) infusion on Day 1 of every 21-day cycle
paclitaxelDrug
Also called Taxol®
Administered as an intravenous (IV) infusion on Day 1 of every 21-day cycle
corticosteroidDrug
Administered PO twice a day (BID) on Days 1-3 of each 21-day cycle

Study groups in NCT00848718
Study group	Role	What they receive
MK-2206 + carboplatin + paclitaxel	Experimental	MK-2206 combined with carboplatin and paclitaxel Receives: Drug: MK-2206; Drug: carboplatin; Drug: paclitaxel
MK-2206 + docetaxel	Experimental	MK-2206 combined with docetaxel plus pretreatment with a corticosteroid Receives: Drug: MK-2206; Drug: docetaxel; Drug: corticosteroid
MK-2206 + erlotinib	Experimental	MK-2206 combined with erlotinib Receives: Drug: MK-2206; Drug: erlotinib

What is being measured

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

Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1
A DLT was any of the following deemed drug related by investigator and graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 criteria: Grade (G)4 hematologic toxicity lasting ≥7 days; G4 thrombocytopenia; G3 or 4 febrile neutropenia and/or infection requiring treatment; G3, 4, 5 non-hematologic toxicity(with the exception of G3 nausea, vomiting, diarrhea, dehydration, or hyperglycemia that as a result of inadequate compliance with supportive care measures; alopecia, inadequately treated hypersensitivity reactions G3 elevated transaminases of ≤1 week in duration); adverse experience (AE) leading to dose reduction; unresolved toxicity causing ≥3 week delay in treatment; ≥G3 hyperglycemia; persistent increases in QTc interval; clinically significant bradycardia; and missing MK-2206 doses due to toxicity. The number of participants who experienced a DLT is presented.
Measured: Cycle 1 (Up to 21 days)
Maximum Tolerated Dose (MTD) of MK-2206 Administered Every Other Day (QOD) in Combination With Carboplatin and Paclitaxel
Participants received MK-2206 (45 or 60 mg) administered PO on Days 1, 3, 5, and 7 in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle. The MTD was determined by the number of participants who experienced a dose limiting toxicity (DLT). DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined.
Measured: Cycle 1 (Up to 21 days)
MTD of MK-2206 Administered Every Three Weeks (Q3W) in Combination With Carboplatin and Paclitaxel
Participants received MK-2206 (90, 135, or 200 mg) administered PO in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle. The MTD was determined by the number of participants who experienced a DLT. DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined.
Measured: Cycle 1 (up to 21 days)
MTD of MK-2206 Administered QOD in Combination With Docetaxel
Participants received MK-2206 45 mg administered PO on Days 1, 3, 5, and 7 in combination with Docetaxel 75 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily. The MTD was determined by the number of participants who experienced a DLT. DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined.
Measured: Cycle 1 (up to 21 days)
MTD of MK-2206 Administered Q3W in Combination With Docetaxel
Participants received MK-2206 (90, 135, or 200 mg) administered PO on Day 1 in combination with Docetaxel 60 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily. The MTD was determined by the number of participants who experienced a DLT. DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined.
Measured: Cycle 1 (up to 21 days)
MTD of MK-2206 Administered QOD in Combination With Erlotinib
Participants received MK-2206 45 mg administered PO every other day (Days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19 and 21) in combination with Erlotinib (100 or 150 mg) administered PO once every day of each 21-day cycle. The MTD was determined by the number of participants who experienced a DLT. DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined.
Measured: Cycle 1 (up to 21 days)
MTD of MK-2206 Administered Once Every Week (QW) in Combination With Erlotinib
Participants received MK-2206 135 mg administered PO on Days 1, 8 and 15 in combination with Erlotinib (100 or 150 mg) administered PO once every day of each 21-day cycle. The MTD was determined by the number of participants who experienced a DLT. DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined.
Measured: Cycle 1 (up to 21 days)
Maximum Plasma Concentration of MK-2206 (Cmax)
Blood samples are to be collected at specified time points according to arm and schedule: QOD schedule for MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48 hours(h) postdose); Q3W schedule MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48, 96h postdose); QOD schedule for the MK-2206+erlotinib (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); and QW schedule for MK-2206+erlotinib (Cycles 1 Day 1: predose and 2, 4, 6, 10, 24, 48, 96h postdose) for the determination of MK-2206 Cmax after Dose 1. The Cmax of MK-2206 after Dose 1 will be presented.
Measured: At designated time points on Cycle 1 Day 1 (Up to 96 hours)
Time to Maximum Plasma Concentration of MK-2206 (Tmax)
Blood samples are to be collected at specified time points according to arm and schedule: QOD schedule for MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48 hours(h) postdose); Q3W schedule MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48, 96h postdose); QOD schedule for the MK-2206+erlotinib (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); and QW schedule for MK-2206+erlotinib (Cycles 1 Day 1: predose and 2, 4, 6, 10, 24, 48, 96h postdose) for the determination of MK-2206 Tmax after Dose 1. The Tmax of MK-2206 after Dose 1 will be presented.
Measured: At designated time points on Cycle 1 Day 1 (Up to 96 hours)
Minimum Plasma Concentration of MK-2206 (Ctrough)
Blood samples are to be collected at specified time points according to arm and schedule: QOD schedule for MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48 hours(h) postdose); Q3W schedule MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); QOD schedule for the MK-2206+erlotinib (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); and QW schedule for MK-2206+erlotinib (Cycles 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose) for the determination of MK-2206 Ctrough after Dose 1. The Ctrough after Dose 1 is presented and is the 48-hour postdose concentration.
Measured: At designated time points on Cycle 1 Day 1 (Up to 48 hours)
Area Under the MK-2206 Concentration Versus Time Curve From Time Zero to 48 Hours Postdose (AUC 0-48h)
Blood samples are to be collected at specified time points according to arm and schedule: QOD schedule for MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48 hours(h) postdose); Q3W schedule MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); QOD schedule for the MK-2206+erlotinib (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); and QW schedule for MK-2206+erlotinib (Cycles 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose) for the determination of MK-2206 AUC0-48h after Dose 1. The AUC0-48h after Dose 1 is presented.
Measured: At designated time points on Cycle 1 Day 1 (Up to 48 hours)

Secondary outcomes (1)

Number of Participants Who Had a Tumor Response of Complete Response (CR) or Partial Response (PR)
Tumor response was assessed using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) and was recorded from the start of the study treatment until the end of treatment. Response categories included: Complete Response (CR): disappearance of all target lesions and Partial Response (PR): at least a 30% decrease in the sum of diameters of target lesions. The number of participants who had a tumor response of either CR or PR is presented.
Measured: Up to approximately 4 months (6 cycles)

Timeline

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

17 Mar 200917 May 2012

First posted20 Feb 2009 (estimated)
Study start17 Mar 2009
Primary completion19 May 2011
Study completion17 May 2012

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 (1)Papers the sponsor has linked to this study.
Other trials for Locally Advanced, Metastatic Solid 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: 77 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00848718
Sponsor's protocol ID: 2206-003
Other IDs: 2009_547, MK-2206-003
Status last verified: Nov 2019
First submitted: 19 Feb 2009
Last updated: 12 Nov 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Publications

Molife LR, Yan L, Vitfell-Rasmussen J, Zernhelt AM, Sullivan DM, Cassier PA, Chen E, Biondo A, Tetteh E, Siu LL, Patnaik A, Papadopoulos KP, de Bono JS, Tolcher AW, Minton S. Phase 1 trial of the oral AKT inhibitor MK-2206 plus carboplatin/paclitaxel, docetaxel, or erlotinib in patients with advanced solid tumors. J Hematol Oncol. 2014 Jan 3;7:1. doi: 10.1186/1756-8722-7-1.
PubMed 24387695

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

RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
RecruitingPhase 1/2
A Study of Neladalkib (NVL-655) in Patients With Advanced NSCLC and Other Solid Tumors Harboring ALK Rearrangement or Activating ALK Mutation (ALKOVE-1)
Locally Advanced Solid Tumor, Metastatic Solid Tumor
RecruitingPhase 1
A Study to Investigate the Safety, Pharmacokinetics, and Preliminary Efficacy of IDE574 Therapy in Adult Participants With Advanced Solid Tumors
Cancer
Active, not recruitingPhase 2
Measuring the Effects of Talazoparib in Patients With Advanced Cancer and DNA Repair Variations
Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IV Breast Cancer AJCC v8
Active, not recruitingPhase 1
A Study to Evaluate the Safety, Pharmacokinetics, and Activity of RO7566802 as a Single Agent and in Combination With Atezolizumab in Participants With Locally Advanced or Metastatic Solid Tumors
Locally Advanced Solid Tumors, Recurrent Solid Tumors

All Locally Advanced, Metastatic Solid Tumors trials

Study at a glance

From the registry record, last updated by the sponsor on 12 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I Dose Escalation Study of MK-2206 in Combination With Standard Doses of Selected Chemotherapies or Targeted Agents in Patients With Locally Advanced or Metastatic Solid Tumors
ClinicalTrials.gov ID: NCT00848718
Acronym / sponsor ID: 2206-003
Conditions: Locally Advanced, Metastatic Solid Tumors
Keywords: Tumors, cancer
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 77 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 17 Mar 2009 (actual)
Primary completion: 19 May 2011 (actual)
Study completion: 17 May 2012 (actual)
First posted: 20 Feb 2009 (estimated)
Results: Posted 12 Nov 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: 3

Arm	Type	Receives
MK-2206 + carboplatin + paclitaxel	Experimental	Drug: MK-2206, Drug: carboplatin, Drug: paclitaxelMK-2206 combined with carboplatin and paclitaxel
MK-2206 + docetaxel	Experimental	Drug: MK-2206, Drug: docetaxel, Drug: corticosteroidMK-2206 combined with docetaxel plus pretreatment with a corticosteroid
MK-2206 + erlotinib	Experimental	Drug: MK-2206, Drug: erlotinibMK-2206 combined with erlotinib

Who may qualify

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

Key inclusion criteria (6 listed)

Participants must have locally advanced or metastatic solid tumors.
Participant is male or female greater than or equal to 18 years of age.
Participant must have a performance status less than or equal to 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
Female participants of childbearing potential has a negative serum or urine pregnancy test within 72 hours prior to receiving the first dose of study medication.
Participants in the MK-2206 + carboplatin/paclitaxel and MK-2206 + docetaxel treatment arms will be limited to no more than 3 prior cytotoxic therapies for metastatic or recurrent diseases.

Key exclusion criteria (19 listed)

Participant has had chemotherapy, radiotherapy or biological therapy within 4 weeks.
Participants must be least 4 weeks post-surgery and do not expect major surgery in the study duration.
Participant is currently participating or has participated in a study with an investigational compound or device within 30 days.
Participant has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
Participant with a primary central nervous system tumor.

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 given by mouth (PO) on Days 1, 3, 5, and 7 of each 21-day cycle (30 mg, 45 mg, or 60 mg) OR MK-2206 PO on Day 1 of each 21-day cycle (60 mg, 90 mg, 135 mg, 200 mg , or 250 mg)	Drug	MK-2206 + carboplatin + paclitaxel, MK-2206 + docetaxel, MK-2206 + erlotinib
docetaxelAlso: Taxotere®Administered as an IV infusion on Day 1 of each 21-day cycle	Drug	MK-2206 + docetaxel
erlotinibAlso: Tarceva®Administered daily (QD) PO in each 21-day cycle	Drug	MK-2206 + erlotinib
carboplatinAlso: Paraplatin®Administered as an intravenous (IV) infusion on Day 1 of every 21-day cycle	Drug	MK-2206 + carboplatin + paclitaxel
paclitaxelAlso: Taxol®Administered as an intravenous (IV) infusion on Day 1 of every 21-day cycle	Drug	MK-2206 + carboplatin + paclitaxel
corticosteroidAdministered PO twice a day (BID) on Days 1-3 of each 21-day cycle	Drug	MK-2206 + docetaxel

Primary outcome

Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1
Time frame: Cycle 1 (Up to 21 days)
A DLT was any of the following deemed drug related by investigator and graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 criteria: Grade (G)4 hematologic toxicity lasting ≥7 days; G4 thrombocytopenia; G3 or 4 febrile neutropenia and/or infection requiring treatment; G3, 4, 5 non-hematologic toxicity(with the exception of G3 nausea, vomiting, diarrhea, dehydration, or hyperglycemia that as a result of inadequate compliance with supportive care measures; alopecia, inadequately treated hypersensitivity reactions G3 elevated transaminases of ≤1 week in duration); adverse experience (AE) leading to dose reduction; unresolved toxicity causing ≥3 week delay in treatment; ≥G3 hyperglycemia; persistent increases in QTc interval; clinically significant bradycardia; and missing MK-2206 doses due to toxicity. The number of participants who experienced a DLT is presented.
Maximum Tolerated Dose (MTD) of MK-2206 Administered Every Other Day (QOD) in Combination With Carboplatin and Paclitaxel
Time frame: Cycle 1 (Up to 21 days)
Participants received MK-2206 (45 or 60 mg) administered PO on Days 1, 3, 5, and 7 in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle. The MTD was determined by the number of participants who experienced a dose limiting toxicity (DLT). DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined.
MTD of MK-2206 Administered Every Three Weeks (Q3W) in Combination With Carboplatin and Paclitaxel
Time frame: Cycle 1 (up to 21 days)
Participants received MK-2206 (90, 135, or 200 mg) administered PO in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle. The MTD was determined by the number of participants who experienced a DLT. DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined.
MTD of MK-2206 Administered QOD in Combination With Docetaxel
Time frame: Cycle 1 (up to 21 days)
Participants received MK-2206 45 mg administered PO on Days 1, 3, 5, and 7 in combination with Docetaxel 75 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily. The MTD was determined by the number of participants who experienced a DLT. DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined.
MTD of MK-2206 Administered Q3W in Combination With Docetaxel
Time frame: Cycle 1 (up to 21 days)
Participants received MK-2206 (90, 135, or 200 mg) administered PO on Day 1 in combination with Docetaxel 60 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily. The MTD was determined by the number of participants who experienced a DLT. DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined.
MTD of MK-2206 Administered QOD in Combination With Erlotinib
Time frame: Cycle 1 (up to 21 days)
Participants received MK-2206 45 mg administered PO every other day (Days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19 and 21) in combination with Erlotinib (100 or 150 mg) administered PO once every day of each 21-day cycle. The MTD was determined by the number of participants who experienced a DLT. DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined.
MTD of MK-2206 Administered Once Every Week (QW) in Combination With Erlotinib
Time frame: Cycle 1 (up to 21 days)
Participants received MK-2206 135 mg administered PO on Days 1, 8 and 15 in combination with Erlotinib (100 or 150 mg) administered PO once every day of each 21-day cycle. The MTD was determined by the number of participants who experienced a DLT. DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined.
Maximum Plasma Concentration of MK-2206 (Cmax)
Time frame: At designated time points on Cycle 1 Day 1 (Up to 96 hours)
Blood samples are to be collected at specified time points according to arm and schedule: QOD schedule for MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48 hours(h) postdose); Q3W schedule MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48, 96h postdose); QOD schedule for the MK-2206+erlotinib (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); and QW schedule for MK-2206+erlotinib (Cycles 1 Day 1: predose and 2, 4, 6, 10, 24, 48, 96h postdose) for the determination of MK-2206 Cmax after Dose 1. The Cmax of MK-2206 after Dose 1 will be presented.
Time to Maximum Plasma Concentration of MK-2206 (Tmax)
Time frame: At designated time points on Cycle 1 Day 1 (Up to 96 hours)
Blood samples are to be collected at specified time points according to arm and schedule: QOD schedule for MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48 hours(h) postdose); Q3W schedule MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48, 96h postdose); QOD schedule for the MK-2206+erlotinib (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); and QW schedule for MK-2206+erlotinib (Cycles 1 Day 1: predose and 2, 4, 6, 10, 24, 48, 96h postdose) for the determination of MK-2206 Tmax after Dose 1. The Tmax of MK-2206 after Dose 1 will be presented.
Minimum Plasma Concentration of MK-2206 (Ctrough)
Time frame: At designated time points on Cycle 1 Day 1 (Up to 48 hours)
Blood samples are to be collected at specified time points according to arm and schedule: QOD schedule for MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48 hours(h) postdose); Q3W schedule MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); QOD schedule for the MK-2206+erlotinib (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); and QW schedule for MK-2206+erlotinib (Cycles 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose) for the determination of MK-2206 Ctrough after Dose 1. The Ctrough after Dose 1 is presented and is the 48-hour postdose concentration.
Area Under the MK-2206 Concentration Versus Time Curve From Time Zero to 48 Hours Postdose (AUC 0-48h)
Time frame: At designated time points on Cycle 1 Day 1 (Up to 48 hours)
Blood samples are to be collected at specified time points according to arm and schedule: QOD schedule for MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48 hours(h) postdose); Q3W schedule MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); QOD schedule for the MK-2206+erlotinib (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); and QW schedule for MK-2206+erlotinib (Cycles 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose) for the determination of MK-2206 AUC0-48h after Dose 1. The AUC0-48h after Dose 1 is presented.

1 secondary outcome

Number of Participants Who Had a Tumor Response of Complete Response (CR) or Partial Response (PR)
Time frame: Up to approximately 4 months (6 cycles)

Results and safety

Results posted to the registry on 12 Nov 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 45 mg QOD+Carboplatin+Paclitaxel	7	0
MK-2206 60 mg QOD+Carboplatin+Paclitaxel	9	0
MK-2206 90 mg Q3W+Carboplatin+Paclitaxel	6	0
MK-2206 135 mg Q3W+Carboplatin+Paclitaxel	5	0
MK-2206 200 mg Q3W+Carboplatin+Paclitaxel	6	0
MK-2206 45 mg QOD+Docetaxel 75 mg/m^2	5	0
MK-2206 90 mg Q3W+Docetaxel 60 mg/m^2	3	0
MK-2206 135 mg Q3W+Docetaxel 60 mg/m^2	5	0
MK-2206 200 mg Q3W+Docetaxel 60 mg/m^2	4	0
MK-2206 45 mg QOD+Erlotinib 100 mg	9	0
MK-2206 45 mg QOD+Erlotinib 150 mg	4	0
MK-2206 135 mg QW+Erlotinib 100 mg	6	0
MK-2206 135 mg QW+Erlotinib 150 mg	8	0

Primary outcome: Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1

Time frame: Cycle 1 (Up to 21 days). Count of participants. Unit: Participants

Measure	MK-2206 45 mg QOD+Carboplatin+Paclitaxel n = 6	MK-2206 60 mg QOD+Carboplatin+Paclitaxel n = 9	MK-2206 90 mg Q3W+Carboplatin+Paclitaxel n = 5	MK-2206 135 mg Q3W+Carboplatin+Paclitaxel n = 5	MK-2206 200 mg Q3W+Carboplatin+Paclitaxel n = 6	MK-2206 45 mg QOD+Docetaxel 75 mg/m^2 n = 5	MK-2206 90 mg Q3W+Docetaxel 60 mg/m^2 n = 3	MK-2206 135 mg Q3W+Docetaxel 60 mg/m^2 n = 4	MK-2206 200 mg Q3W+Docetaxel 60 mg/m^2 n = 4	MK-2206 45 mg QOD+Erlotinib 100 mg n = 9	MK-2206 45 mg QOD+Erlotinib 150 mg n = 4	MK-2206 135 mg QW+Erlotinib 100 mg n = 6	MK-2206 135 mg QW+Erlotinib 150 mg n = 6
Value	1	2	1	1	2	3	0	0	1	2	1	0	1

Population analysed: All participants that have received one dose of study treatment

Primary outcome: Maximum Tolerated Dose (MTD) of MK-2206 Administered Every Other Day (QOD) in Combination With Carboplatin and Paclitaxel

Time frame: Cycle 1 (Up to 21 days). Number. Unit: mg

Measure	MK-2206 Administered QOD+Carboplatin+Paclitaxel n = 9
Value	NA

Population analysed: All participants who received MK-2206 QOD+carboplatin+paclitaxel and had a DLT in Cycle 1 or received 90% of the planned doses and completed all safety evaluations ≤21 days after the first administration of treatment without experiencing a DLT. MTD could not be determined according to pre-defined protocol criteria based on the enrollment number.

Primary outcome: MTD of MK-2206 Administered Every Three Weeks (Q3W) in Combination With Carboplatin and Paclitaxel

Time frame: Cycle 1 (up to 21 days). Number. Unit: mg

Measure	MK-2206 Administered Q3W+Carboplatin+Paclitaxel n = 15
Value	NA

Population analysed: All participants who received MK-2206 Q3W+carboplatin+paclitaxel and had a DLT in Cycle 1 or received 90% of the planned doses and completed all safety evaluations ≤21 days after the first administration of treatment without experiencing a DLT. MTD could not be determined according to pre-defined protocol criteria based on the enrollment number.

Primary outcome: MTD of MK-2206 Administered QOD in Combination With Docetaxel

Time frame: Cycle 1 (up to 21 days). Number. Unit: mg

Measure	MK-2206 Administered QOD+Docetaxel n = 5
Value	NA

Population analysed: All participants who received MK-2206 QOD+docetaxel and had a DLT in Cycle 1 or received 90% of the planned doses and completed all safety evaluations ≤21 days after the first administration of treatment without experiencing a DLT. MTD could not be determined according to pre-defined protocol criteria based on the enrollment number.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Up to approximately 14 months (Up to 30 days after last dose of study treatment). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
MK-2206 45 mg QOD+Carboplatin+Paclitaxel	2 of 6 (33.3%)	6 of 6 (100%)	0 of 6
MK-2206 60 mg QOD+Carboplatin+Paclitaxel	8 of 9 (88.9%)	8 of 9 (88.9%)	1 of 9
MK-2206 90 mg Q3W+Carboplatin+Paclitaxel	3 of 5 (60%)	5 of 5 (100%)	0 of 5
MK-2206 135 mg Q3W+Carboplatin+Paclitaxel	1 of 5 (20%)	5 of 5 (100%)	0 of 5
MK-2206 200 mg Q3W+Carboplatin+Paclitaxel	2 of 6 (33.3%)	5 of 6 (83.3%)	0 of 6
MK-2206 45 mg QOD+Docetaxel 75 mg/m2	5 of 5 (100%)	5 of 5 (100%)	1 of 5
MK-2206 90 mg Q3W+Docetaxel 60 mg/m2	1 of 3 (33.3%)	3 of 3 (100%)	0 of 3
MK-2206 135 mg Q3W+Docetaxel 60 mg/m2	3 of 4 (75%)	3 of 4 (75%)	0 of 4
MK-2206 200 mg Q3W+Docetaxel 60 mg/m2	3 of 4 (75%)	4 of 4 (100%)	0 of 4
MK-2206 45 mg QOD+Erlotinib 100 mg	6 of 9 (66.7%)	9 of 9 (100%)	1 of 9
MK-2206 45 mg QOD+Erlotinib 150 mg	1 of 4 (25%)	4 of 4 (100%)	0 of 4
MK-2206 135 mg QW+Erlotinib 100 mg	4 of 6 (66.7%)	6 of 6 (100%)	1 of 6
MK-2206 135 mg QW+Erlotinib 150 mg	5 of 6 (83.3%)	6 of 6 (100%)	1 of 6

Limitations and caveats (from the sponsor): Enrollment in this study was discontinued with Amendment 5.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Nov 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 24387695Molife LR, Yan L, Vitfell-Rasmussen J, Zernhelt AM, Sullivan DM, Cassier PA, Chen E, Biondo A, Tetteh E, Siu LL, Patnaik A, Papadopoulos KP, de Bono JS, Tolcher AW, Minton S. Phase 1 trial of the oral AKT inhibitor MK-2206 plus carboplatin/paclitaxel, docetaxel, or erlotinib in patients with advanced solid tumors. J Hematol Oncol. 2014 Jan 3;7:1. doi: 10.1186/1756-8722-7-1.
Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/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 Director study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing MK-2206, docetaxel and erlotinib in people with Locally Advanced, 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 6 inclusion and 19 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 12 Nov 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 12 Nov 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 Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1 (time frame: Cycle 1 (Up to 21 days)). The study lists 11 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 NCT00848718, 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 12 Nov 2019.