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CompletedNCT00848718Updated Nov 12, 2019Results posted

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 interventional study of MK-2206 and docetaxel in Locally Advanced, Metastatic Solid Tumors, sponsored by Merck Sharp & Dohme LLC. Completed. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-11-12.

Sponsored by Merck Sharp & Dohme LLC · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
77
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study 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.

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.

02

Conditions studied

  • Locally Advanced, Metastatic Solid Tumors

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Keywords

  • Tumors, cancer
03

In context

Neoplasms

9,365 studies on the registry are indexed under Neoplasms; 2,489 are open to participants now.

This study's enrollment of 77 is above the median of 50 across 7,253 interventional studies indexed under Neoplasms.

Browse Neoplasms studies →

Lead sponsor

Merck Sharp & Dohme LLC is the lead sponsor of 2,114 studies on the registry; 133 are open to participants now.

Of its 489 completed or terminated interventional studies of FDA-regulated products, 362 (74%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • 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.

Exclusion criteria

Exclusion Criteria:

  • 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.
  • 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.
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
77 participants (actual)

Study arms

  • Experimental
    MK-2206 + carboplatin + paclitaxel

    MK-2206 combined with carboplatin and paclitaxel

    Drug: MK-2206 · Drug: carboplatin · Drug: paclitaxel

  • Experimental
    MK-2206 + docetaxel

    MK-2206 combined with docetaxel plus pretreatment with a corticosteroid

    Drug: MK-2206 · Drug: docetaxel · Drug: corticosteroid

  • Experimental
    MK-2206 + erlotinib

    MK-2206 combined with erlotinib

    Drug: MK-2206 · Drug: erlotinib

Interventions

  • DrugMK-2206

    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)

  • Drugdocetaxel

    Administered as an IV infusion on Day 1 of each 21-day cycle

    Also known as: Taxotere®

  • Drugerlotinib

    Administered daily (QD) PO in each 21-day cycle

    Also known as: Tarceva®

  • Drugcarboplatin

    Administered as an intravenous (IV) infusion on Day 1 of every 21-day cycle

    Also known as: Paraplatin®

  • Drugpaclitaxel

    Administered as an intravenous (IV) infusion on Day 1 of every 21-day cycle

    Also known as: Taxol®

  • Drugcorticosteroid

    Administered PO twice a day (BID) on Days 1-3 of each 21-day cycle

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Cycle 1 (Up to 21 days)

  2. 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.

    Time frame: Cycle 1 (Up to 21 days)

  3. 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.

    Time frame: Cycle 1 (up to 21 days)

  4. 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.

    Time frame: Cycle 1 (up to 21 days)

  5. 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.

    Time frame: Cycle 1 (up to 21 days)

  6. 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.

    Time frame: Cycle 1 (up to 21 days)

  7. 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.

    Time frame: Cycle 1 (up to 21 days)

  8. 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.

    Time frame: At designated time points on Cycle 1 Day 1 (Up to 96 hours)

  9. 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.

    Time frame: At designated time points on Cycle 1 Day 1 (Up to 96 hours)

  10. 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.

    Time frame: At designated time points on Cycle 1 Day 1 (Up to 48 hours)

  11. 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.

    Time frame: 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.

    Time frame: Up to approximately 4 months (6 cycles)

07

Results

Posted Nov 12, 2019
Limitations and caveats
Enrollment in this study was discontinued with Amendment 5.

Participant flow

77 participants were allocated to one of 3 treatment combinations with MK-2206 according to clinical presentation but 5 participants were not treated due to disease progression before initiation of treatment.

Participant flow — Overall Study
MilestoneMK-2206 45 mg QOD+Carboplatin+PaclitaxelMK-2206 60 mg QOD+Carboplatin+PaclitaxelMK-2206 90 mg Q3W+Carboplatin+PaclitaxelMK-2206 135 mg Q3W+Carboplatin+PaclitaxelMK-2206 200 mg Q3W+Carboplatin+PaclitaxelMK-2206 45 mg QOD+Docetaxel 75 mg/m^2MK-2206 90 mg Q3W+Docetaxel 60 mg/m^2MK-2206 135 mg Q3W+Docetaxel 60 mg/m^2MK-2206 200 mg Q3W+Docetaxel 60 mg/m^2MK-2206 45 mg QOD+Erlotinib 100 mgMK-2206 45 mg QOD+Erlotinib 150 mgMK-2206 135 mg QW+Erlotinib 100 mgMK-2206 135 mg QW+Erlotinib 150 mg
Started7965653549468
Treated6955653449466
Completed0000000000000
Not completed7965653549468
Withdrew: Adverse event2211100110002
Withdrew: Lack of efficacy0010001000000
Withdrew: Physician decision0100110012001
Withdrew: Progressive disease before treatment1513442127362
Withdrew: Protocol violation0100000100001
Withdrew: Withdrawal by subject1001000000100
Withdrew: Progressive disease during treatment3030000200002

Outcome measures

PrimaryNumber 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.

Time frame:
Cycle 1 (Up to 21 days)
Reported as:
Count of participants · Participants
Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1
ParticipantsMK-2206 45 mg QOD+Carboplatin+PaclitaxelMK-2206 60 mg QOD+Carboplatin+PaclitaxelMK-2206 90 mg Q3W+Carboplatin+PaclitaxelMK-2206 135 mg Q3W+Carboplatin+PaclitaxelMK-2206 200 mg Q3W+Carboplatin+PaclitaxelMK-2206 45 mg QOD+Docetaxel 75 mg/m^2MK-2206 90 mg Q3W+Docetaxel 60 mg/m^2MK-2206 135 mg Q3W+Docetaxel 60 mg/m^2MK-2206 200 mg Q3W+Docetaxel 60 mg/m^2MK-2206 45 mg QOD+Erlotinib 100 mgMK-2206 45 mg QOD+Erlotinib 150 mgMK-2206 135 mg QW+Erlotinib 100 mgMK-2206 135 mg QW+Erlotinib 150 mg
Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 11211230012101
PrimaryMaximum 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.

Time frame:
Cycle 1 (Up to 21 days)
Reported as:
Number · mg
Maximum Tolerated Dose (MTD) of MK-2206 Administered Every Other Day (QOD) in Combination With Carboplatin and Paclitaxel
mgMK-2206 Administered QOD+Carboplatin+Paclitaxel
Maximum Tolerated Dose (MTD) of MK-2206 Administered Every Other Day (QOD) in Combination With Carboplatin and PaclitaxelNA
PrimaryMTD 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.

Time frame:
Cycle 1 (up to 21 days)
Reported as:
Number · mg
MTD of MK-2206 Administered Every Three Weeks (Q3W) in Combination With Carboplatin and Paclitaxel
mgMK-2206 Administered Q3W+Carboplatin+Paclitaxel
MTD of MK-2206 Administered Every Three Weeks (Q3W) in Combination With Carboplatin and PaclitaxelNA
PrimaryMTD 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.

Time frame:
Cycle 1 (up to 21 days)
Reported as:
Number · mg
MTD of MK-2206 Administered QOD in Combination With Docetaxel
mgMK-2206 Administered QOD+Docetaxel
MTD of MK-2206 Administered QOD in Combination With DocetaxelNA
PrimaryMTD 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.

Time frame:
Cycle 1 (up to 21 days)
Reported as:
Number · mg
MTD of MK-2206 Administered Q3W in Combination With Docetaxel
mgMK-2206 Administered Q3W+Docetaxel
MTD of MK-2206 Administered Q3W in Combination With DocetaxelNA
PrimaryMTD 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.

Time frame:
Cycle 1 (up to 21 days)
Reported as:
Number · mg
MTD of MK-2206 Administered QOD in Combination With Erlotinib
mgMK-2206 Administered QOD+Erlotinib
MTD of MK-2206 Administered QOD in Combination With ErlotinibNA
PrimaryMTD 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.

Time frame:
Cycle 1 (up to 21 days)
Reported as:
Number · mg
MTD of MK-2206 Administered Once Every Week (QW) in Combination With Erlotinib
mgMK-2206 Administered QW+Erlotinib
MTD of MK-2206 Administered Once Every Week (QW) in Combination With ErlotinibNA
PrimaryMaximum 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.

Time frame:
At designated time points on Cycle 1 Day 1 (Up to 96 hours)
Reported as:
Mean · nmol/L
Maximum Plasma Concentration of MK-2206 (Cmax)
nmol/LMK-2206 45 mg QOD+Carboplatin+PaclitaxelMK-2206 60 mg QOD+Carboplatin+PaclitaxelMK-2206 90 mg Q3W+Carboplatin+PaclitaxelMK-2206 135 mg Q3W+Carboplatin+PaclitaxelMK-2206 200 mg Q3W+Carboplatin+PaclitaxelMK-2206 45 mg QOD+Docetaxel 75 mg/m^2MK-2206 90 mg Q3W+Docetaxel 60 mg/m^2MK-2206 135 mg Q3W+Docetaxel 60 mg/m^2MK-2206 200 mg Q3W+Docetaxel 60 mg/m^2MK-2206 45 mg QOD+Erlotinib 100 mgMK-2206 45 mg QOD+Erlotinib 150 mgMK-2206 135 mg QW+Erlotinib 100 mgMK-2206 135 mg QW+Erlotinib 150 mg
Maximum Plasma Concentration of MK-2206 (Cmax)57.7 ± 13.888.3 ± 24.2144 ± 57.0247 ± 52.5431 ± 24942.9 ± 13.3106 ± 42.5278 ± 35.5287 ± 67.648.8 ± 11.265.6 ± 29.3212 ± 75.9244 ± 84.2
PrimaryTime 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.

Time frame:
At designated time points on Cycle 1 Day 1 (Up to 96 hours)
Reported as:
Median · hours
Time to Maximum Plasma Concentration of MK-2206 (Tmax)
hoursMK-2206 45 mg QOD+Carboplatin+PaclitaxelMK-2206 60 mg QOD+Carboplatin+PaclitaxelMK-2206 90 mg Q3W+Carboplatin+PaclitaxelMK-2206 135 mg Q3W+Carboplatin+PaclitaxelMK-2206 200 mg Q3W+Carboplatin+PaclitaxelMK-2206 45 mg QOD+Docetaxel 75 mg/m^2MK-2206 90 mg Q3W+Docetaxel 60 mg/m^2MK-2206 135 mg Q3W+Docetaxel 60 mg/m^2MK-2206 200 mg Q3W+Docetaxel 60 mg/m^2MK-2206 45 mg QOD+Erlotinib 100 mgMK-2206 45 mg QOD+Erlotinib 150 mgMK-2206 135 mg QW+Erlotinib 100 mgMK-2206 135 mg QW+Erlotinib 150 mg
Time to Maximum Plasma Concentration of MK-2206 (Tmax)4.0 (4.0 to 6.0)8.0 (6.0 to 10.0)6.0 (4.0 to 10.0)10.0 (6.0 to 10.0)5.0 (4.0 to 10.0)6.0 (4.0 to 10.0)4.0 (4.0 to 10.0)6.0 (4.0 to 10.0)6.0 (4.0 to 6.0)6.0 (4.0 to 10.0)7.0 (4.0 to 24.0)6.0 (2.0 to 6.0)4.0 (4.0 to 10.0)
PrimaryMinimum 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.

Time frame:
At designated time points on Cycle 1 Day 1 (Up to 48 hours)
Reported as:
Mean · nmol/L
Minimum Plasma Concentration of MK-2206 (Ctrough)
nmol/LMK-2206 45 mg QOD+Carboplatin+PaclitaxelMK-2206 60 mg QOD+Carboplatin+PaclitaxelMK-2206 90 mg Q3W+Carboplatin+PaclitaxelMK-2206 135 mg Q3W+Carboplatin+PaclitaxelMK-2206 200 mg Q3W+Carboplatin+PaclitaxelMK-2206 45 mg QOD+Docetaxel 75 mg/m^2MK-2206 90 mg Q3W+Docetaxel 60 mg/m^2MK-2206 135 mg Q3W+Docetaxel 60 mg/m^2MK-2206 200 mg Q3W+Docetaxel 60 mg/m^2MK-2206 45 mg QOD+Erlotinib 100 mgMK-2206 45 mg QOD+Erlotinib 150 mgMK-2206 135 mg QW+Erlotinib 100 mgMK-2206 135 mg QW+Erlotinib 150 mg
Minimum Plasma Concentration of MK-2206 (Ctrough)24.9 ± 10.740.6 ± 11.21.36 ± 0.8984.67 ± 3.332.21 ± 1.0417.1 ± 3.662.27 ± 1.043.80 ± NA3.24 ± 0.63823.8 ± 8.1236.8 ± 10.696.6 ± 43.695.5 ± 43.1
PrimaryArea 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.

Time frame:
At designated time points on Cycle 1 Day 1 (Up to 48 hours)
Reported as:
Mean · nmol•hr/L
Area Under the MK-2206 Concentration Versus Time Curve From Time Zero to 48 Hours Postdose (AUC 0-48h)
nmol•hr/LMK-2206 45 mg QOD+Carboplatin+PaclitaxelMK-2206 60 mg QOD+Carboplatin+PaclitaxelMK-2206 90 mg Q3W+Carboplatin+PaclitaxelMK-2206 135 mg Q3W+Carboplatin+PaclitaxelMK-2206 200 mg Q3W+Carboplatin+PaclitaxelMK-2206 45 mg QOD+Docetaxel 75 mg/m^2MK-2206 90 mg Q3W+Docetaxel 60 mg/m^2MK-2206 135 mg Q3W+Docetaxel 60 mg/m^2MK-2206 200 mg Q3W+Docetaxel 60 mg/m^2MK-2206 45 mg QOD+Erlotinib 100 mgMK-2206 45 mg QOD+Erlotinib 150 mgMK-2206 135 mg QW+Erlotinib 100 mgMK-2206 135 mg QW+Erlotinib 150 mg
Area Under the MK-2206 Concentration Versus Time Curve From Time Zero to 48 Hours Postdose (AUC 0-48h)1630 ± 4962700 ± 6194130 ± 15207420 ± 12509730 ± 23201320 ± 3953000 ± 12508090 ± 5427690 ± 15501460 ± 4172110 ± 6376420 ± 27606560 ± 2650
SecondaryNumber 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.

Time frame:
Up to approximately 4 months (6 cycles)
Reported as:
Count of participants · Participants
Number of Participants Who Had a Tumor Response of Complete Response (CR) or Partial Response (PR)
ParticipantsMK-2206 45 mg QOD+Carboplatin+PaclitaxelMK-2206 60 mg QOD+Carboplatin+PaclitaxelMK-2206 90 mg Q3W+Carboplatin+PaclitaxelMK-2206 135 mg Q3W+Carboplatin+PaclitaxelMK-2206 200 mg Q3W+Carboplatin+PaclitaxelMK-2206 45 mg QOD+Docetaxel 75 mg/m^2MK-2206 90 mg Q3W+Docetaxel 60 mg/m^2MK-2206 135 mg Q3W+Docetaxel 60 mg/m^2MK-2206 200 mg Q3W+Docetaxel 60 mg/m^2MK-2206 45 mg QOD+Erlotinib 100 mgMK-2206 45 mg QOD+Erlotinib 150 mgMK-2206 135 mg QW+Erlotinib 100 mgMK-2206 135 mg QW+Erlotinib 150 mg
Number of Participants Who Had a Tumor Response of Complete Response (CR) or Partial Response (PR)1301100000000

Adverse events

Collected over Up to approximately 14 months (Up to 30 days after last dose of study treatment). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
MK-2206 45 mg QOD+Carboplatin+Paclitaxel0/6 (0%)2/6 (33.3%)6/6 (100%)
MK-2206 60 mg QOD+Carboplatin+Paclitaxel1/9 (11.1%)8/9 (88.9%)8/9 (88.9%)
MK-2206 90 mg Q3W+Carboplatin+Paclitaxel0/5 (0%)3/5 (60%)5/5 (100%)
MK-2206 135 mg Q3W+Carboplatin+Paclitaxel0/5 (0%)1/5 (20%)5/5 (100%)
MK-2206 200 mg Q3W+Carboplatin+Paclitaxel0/6 (0%)2/6 (33.3%)5/6 (83.3%)
MK-2206 45 mg QOD+Docetaxel 75 mg/m21/5 (20%)5/5 (100%)5/5 (100%)
MK-2206 90 mg Q3W+Docetaxel 60 mg/m20/3 (0%)1/3 (33.3%)3/3 (100%)
MK-2206 135 mg Q3W+Docetaxel 60 mg/m20/4 (0%)3/4 (75%)3/4 (75%)
MK-2206 200 mg Q3W+Docetaxel 60 mg/m20/4 (0%)3/4 (75%)4/4 (100%)
MK-2206 45 mg QOD+Erlotinib 100 mg1/9 (11.1%)6/9 (66.7%)9/9 (100%)
MK-2206 45 mg QOD+Erlotinib 150 mg0/4 (0%)1/4 (25%)4/4 (100%)
MK-2206 135 mg QW+Erlotinib 100 mg1/6 (16.7%)4/6 (66.7%)6/6 (100%)
MK-2206 135 mg QW+Erlotinib 150 mg1/6 (16.7%)5/6 (83.3%)6/6 (100%)
Most frequent serious events
Showing 10 of 46
Most frequent serious events
EventMK-2206 45 mg QOD+Carboplatin+PaclitaxelMK-2206 60 mg QOD+Carboplatin+PaclitaxelMK-2206 90 mg Q3W+Carboplatin+PaclitaxelMK-2206 135 mg Q3W+Carboplatin+PaclitaxelMK-2206 200 mg Q3W+Carboplatin+PaclitaxelMK-2206 45 mg QOD+Docetaxel 75 mg/m2MK-2206 90 mg Q3W+Docetaxel 60 mg/m2MK-2206 135 mg Q3W+Docetaxel 60 mg/m2MK-2206 200 mg Q3W+Docetaxel 60 mg/m2MK-2206 45 mg QOD+Erlotinib 100 mgMK-2206 45 mg QOD+Erlotinib 150 mgMK-2206 135 mg QW+Erlotinib 100 mgMK-2206 135 mg QW+Erlotinib 150 mg
Febrile neutropeniaBlood and lymphatic system disorders0/62/91/50/50/63/50/30/40/40/90/40/60/6
Pleural effusionRespiratory, thoracic and mediastinal disorders0/61/90/50/50/62/50/30/40/40/90/40/60/6
Retinal vein occlusionEye disorders0/60/90/50/50/60/51/30/40/40/90/40/60/6
DiarrhoeaGastrointestinal disorders0/60/90/50/50/60/50/30/40/41/90/40/62/6
StomatitisGastrointestinal disorders0/60/90/50/50/60/50/30/40/40/90/40/62/6
PyrexiaGeneral disorders0/60/90/50/50/60/50/30/40/40/90/42/61/6
TinnitusEar and labyrinth disorders0/60/90/50/50/60/50/30/41/40/90/40/60/6
Abdominal painGastrointestinal disorders1/60/90/50/50/60/50/31/41/41/90/40/61/6
InfectionInfections and infestations0/60/90/50/50/60/50/30/40/40/91/40/61/6
Neutropenic sepsisInfections and infestations0/61/90/50/50/60/50/30/41/40/90/40/60/6
Most frequent other events
Showing 10 of 227
Most frequent other events
EventMK-2206 45 mg QOD+Carboplatin+PaclitaxelMK-2206 60 mg QOD+Carboplatin+PaclitaxelMK-2206 90 mg Q3W+Carboplatin+PaclitaxelMK-2206 135 mg Q3W+Carboplatin+PaclitaxelMK-2206 200 mg Q3W+Carboplatin+PaclitaxelMK-2206 45 mg QOD+Docetaxel 75 mg/m2MK-2206 90 mg Q3W+Docetaxel 60 mg/m2MK-2206 135 mg Q3W+Docetaxel 60 mg/m2MK-2206 200 mg Q3W+Docetaxel 60 mg/m2MK-2206 45 mg QOD+Erlotinib 100 mgMK-2206 45 mg QOD+Erlotinib 150 mgMK-2206 135 mg QW+Erlotinib 100 mgMK-2206 135 mg QW+Erlotinib 150 mg
NauseaGastrointestinal disorders3/66/93/52/54/62/51/31/42/43/94/41/62/6
FatigueGeneral disorders4/66/94/55/51/64/53/32/44/45/93/43/64/6
Decreased appetiteMetabolism and nutrition disorders2/65/92/53/52/62/50/32/41/42/94/42/64/6
AlopeciaSkin and subcutaneous tissue disorders4/66/95/54/52/63/51/31/42/40/90/41/60/6
DiarrhoeaGastrointestinal disorders1/64/92/51/52/61/52/30/42/45/93/44/65/6
DyspnoeaRespiratory, thoracic and mediastinal disorders1/63/91/52/50/62/50/31/41/40/91/42/65/6
LeukopeniaBlood and lymphatic system disorders1/66/94/54/51/61/51/30/41/40/90/40/60/6
NeutropeniaBlood and lymphatic system disorders1/65/94/53/51/63/52/30/41/40/90/40/60/6
DehydrationMetabolism and nutrition disorders1/61/91/54/52/62/51/30/40/40/91/40/60/6
Neuropathy peripheralNervous system disorders0/64/94/53/50/60/50/31/41/40/90/40/60/6

Baseline characteristics

All participants who were allocated to receive treatment.

Age, Continuous
Age, Continuous(Years)MK-2206 45 mg QOD+Carboplatin+PaclitaxelMK-2206 60 mg QOD+Carboplatin+PaclitaxelMK-2206 90 mg Q3W+Carboplatin+PaclitaxelMK-2206 135 mg Q3W+Carboplatin+PaclitaxelMK-2206 200 mg Q3W+Carboplatin+PaclitaxelMK-2206 45 mg QOD+Docetaxel 75 mg/m^2MK-2206 90 mg Q3W+Docetaxel 60 mg/m^2MK-2206 135 mg Q3W+Docetaxel 60 mg/m^2MK-2206 200 mg Q3W+Docetaxel 60 mg/m^2MK-2206 45 mg QOD+Erlotinib 100 mgMK-2206 45 mg QOD+Erlotinib 150 mgMK-2206 135 mg QW+Erlotinib 100 mgMK-2206 135 mg QW+Erlotinib 150 mgTotal
Mean51.6 ± 15.358.4 ± 13.656.2 ± 10.463.6 ± 7.838.8 ± 12.457.4 ± 19.764.7 ± 12.057.4 ± 8.054.0 ± 9.461.6 ± 6.161.0 ± 6.455.7 ± 12.754.1 ± 10.956.2 ± 12.4
Sex: Female, Male
Sex: Female, Male(Participants)MK-2206 45 mg QOD+Carboplatin+PaclitaxelMK-2206 60 mg QOD+Carboplatin+PaclitaxelMK-2206 90 mg Q3W+Carboplatin+PaclitaxelMK-2206 135 mg Q3W+Carboplatin+PaclitaxelMK-2206 200 mg Q3W+Carboplatin+PaclitaxelMK-2206 45 mg QOD+Docetaxel 75 mg/m^2MK-2206 90 mg Q3W+Docetaxel 60 mg/m^2MK-2206 135 mg Q3W+Docetaxel 60 mg/m^2MK-2206 200 mg Q3W+Docetaxel 60 mg/m^2MK-2206 45 mg QOD+Erlotinib 100 mgMK-2206 45 mg QOD+Erlotinib 150 mgMK-2206 135 mg QW+Erlotinib 100 mgMK-2206 135 mg QW+Erlotinib 150 mgTotal
Female462412143212436
Male334153211734441
Race (NIH/OMB)
Race (NIH/OMB)(Participants)MK-2206 45 mg QOD+Carboplatin+PaclitaxelMK-2206 60 mg QOD+Carboplatin+PaclitaxelMK-2206 90 mg Q3W+Carboplatin+PaclitaxelMK-2206 135 mg Q3W+Carboplatin+PaclitaxelMK-2206 200 mg Q3W+Carboplatin+PaclitaxelMK-2206 45 mg QOD+Docetaxel 75 mg/m^2MK-2206 90 mg Q3W+Docetaxel 60 mg/m^2MK-2206 135 mg Q3W+Docetaxel 60 mg/m^2MK-2206 200 mg Q3W+Docetaxel 60 mg/m^2MK-2206 45 mg QOD+Erlotinib 100 mgMK-2206 45 mg QOD+Erlotinib 150 mgMK-2206 135 mg QW+Erlotinib 100 mgMK-2206 135 mg QW+Erlotinib 150 mgTotal
American Indian or Alaska Native00000000000000
Asian00001100010003
Native Hawaiian or Other Pacific Islander00000000000000
Black or African American01001000000002
White786544354846872
More than one race00000000000000
Unknown or Not Reported00000000000000
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Study locations

No study locations are listed for this record.

09

References and documents

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 ↗

Individual participant data

Plan to share: Yes — https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Nov 12, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT00848718
Lead sponsor
Merck Sharp & Dohme LLC
Responsible party
Sponsor
First posted
Feb 20, 2009
Start date
Mar 17, 2009
Primary completion
May 19, 2011
Completion
May 17, 2012
Results posted
Nov 12, 2019
Last update
Nov 12, 2019

Study contacts

Medical Director
study director · Merck Sharp & Dohme LLC

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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