A Study of MK-2206 in Combination With Trastuzumab and Lapatinib for the Treatment of HER2+ Solid Tumors (MK-2206-015)

May 20, 2024 updated by: Merck Sharp & Dohme LLC

A Phase I Investigation of the Combination of MK-2206, Trastuzumab and Lapatinib in HER2+ Solid Tumors

This study will assess the safety, tolerability, and the maximum tolerated dose (MTD) of MK-2206 in combination with both trastuzumab and trastuzumab/lapatinib in participants with human epidermal growth factor receptor 2 positive (HER2+) breast cancer and other solid tumors. The primary hypothesis of this study is that the combination of oral MK-2206 with trastuzumab or with trastuzumab/lapatinib will be well tolerated in participants with advanced HER2+ solid tumors.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This study was divided into 2 parts. In Part 1, cohorts of 3 participants were to be enrolled sequentially on escalating doses of MK-2206 in combination with a fixed dose of trastuzumab. Barring dose-limiting toxicities (DLTs), additional participants were to be enrolled and dose-finding would proceed until an MTD was identified for MK-2206 when dosed either every other day (QOD) or once weekly (QW) in combination with trastuzumab. In Part 2, cohorts of 3 participants were to be enrolled sequentially on rising doses of lapatinib administered in combination with the MTD dose of MK-2206/trastuzumab established in Part 1. Barring DLTs, dose finding would proceed until an MTD of the 3-drug combination was identified.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
33

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Have a histologically or cytologically-confirmed locally advanced or metastatic HER2+ solid tumor.
  • Have performance status ≤1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
  • Have adequate organ function.
  • Female participants have a negative pregnancy test 72 hours prior to receiving the first dose of study medication.
  • Have completed any major surgery for a minimum of 28 days prior to enrollment in this study.
  • Able to swallow tablets and has no surgical or anatomical condition that will preclude the patient from swallowing or absorbing oral medications on an ongoing basis.

Exclusion Criteria:

  • Had chemotherapy, radiotherapy or biological therapy within 4 weeks of screening. Participants receiving trastuzumab and/or lapatinib prior to screening must be off both medications for 1 week prior to first dose of MK-2206 if trastuzumab had been administered at 2 mg/kg weekly and 3 weeks if trastuzumab had been administered at 6 mg/kg weekly.
  • Currently participating or has participated in a study with an investigational compound or device within 30 days, or 5x half-life from prior agents, whichever is longer, of Day 1 of this study
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
  • Has a primary CNS tumor.
  • Has known hypersensitivity to the components of study drugs or its analogs.
  • Has a history or evidence of heart disease.
  • Has uncontrolled hypertension or diabetes.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Is pregnant or breastfeeding or is expecting to conceive or father children during the study.
  • Is HIV positive.
  • Has symptomatic ascites or pleural effusion.
  • Is receiving treatment with oral corticosteroids for reason other than CNS metastasis.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Pt. 1: MK-2206 45mg, QOD + Trastuzumab
Participants in Part 1 (Pt. 1) receive MK-2206 45 mg every other day (QOD), taken orally. In combination with MK-2206, trastuzumab is administered by intravenous (IV) infusion at an initial dose of 8 mg/kg (loading dose) followed by 6 mg/kg every 3 weeks (q3wk).
Drug: MK-2206
[Part 1]: MK-2206 tablets will be given starting at a dose of 45 mg QOD and escalated to 60 mg QOD if tolerated, OR starting at a dose of 135 mg QW and escalated to 200 mg QW if tolerated. Dose reduction to 30mg QOD or 90 mg QW may be permitted. The dose of MK2206 will be increased or decreased as required to find the maximum tolerated dose (MTD) of MK2206 for both the QOD and QW dosing schedules in combination with trastuzumab. [Part 2] The Part 2 dosing level and schedule of MK2206 will be chosen from the MTD of either the QOD or QW dosing schedules depending on the toxicity profile and preliminary efficacy.
Biological: Trastuzumab
Trastuzumab will be administered as a 90-minute IV infusion at a loading dose of 8 mg/kg followed by 6 mg/kg q3wk.
Experimental: Pt. 1: MK-2206 60mg, QOD + Trastuzumab
Participants in Pt. 1 receive MK-2206 60 mg QOD, taken orally. In combination with MK-2206, trastuzumab is administered by IV infusion at an initial dose of 8 mg/kg (loading dose) followed by 6 mg/kg q3wk.
Drug: MK-2206
[Part 1]: MK-2206 tablets will be given starting at a dose of 45 mg QOD and escalated to 60 mg QOD if tolerated, OR starting at a dose of 135 mg QW and escalated to 200 mg QW if tolerated. Dose reduction to 30mg QOD or 90 mg QW may be permitted. The dose of MK2206 will be increased or decreased as required to find the maximum tolerated dose (MTD) of MK2206 for both the QOD and QW dosing schedules in combination with trastuzumab. [Part 2] The Part 2 dosing level and schedule of MK2206 will be chosen from the MTD of either the QOD or QW dosing schedules depending on the toxicity profile and preliminary efficacy.
Biological: Trastuzumab
Trastuzumab will be administered as a 90-minute IV infusion at a loading dose of 8 mg/kg followed by 6 mg/kg q3wk.
Experimental: Pt. 1: MK-2206 135mg, QW + Trastuzumab
Participants in Pt. 1 receive MK-2206 135 mg once weekly (QW), taken orally. In combination with MK-2206, trastuzumab is administered by IV infusion at an initial dose of 8 mg/kg (loading dose) followed by 6 mg/kg q3wk.
Drug: MK-2206
[Part 1]: MK-2206 tablets will be given starting at a dose of 45 mg QOD and escalated to 60 mg QOD if tolerated, OR starting at a dose of 135 mg QW and escalated to 200 mg QW if tolerated. Dose reduction to 30mg QOD or 90 mg QW may be permitted. The dose of MK2206 will be increased or decreased as required to find the maximum tolerated dose (MTD) of MK2206 for both the QOD and QW dosing schedules in combination with trastuzumab. [Part 2] The Part 2 dosing level and schedule of MK2206 will be chosen from the MTD of either the QOD or QW dosing schedules depending on the toxicity profile and preliminary efficacy.
Biological: Trastuzumab
Trastuzumab will be administered as a 90-minute IV infusion at a loading dose of 8 mg/kg followed by 6 mg/kg q3wk.
Experimental: Pt. 1: MK-2206 200mg, QW + Trastuzumab
Participants in Pt. 1 receive MK-2206 200 mg QW, taken orally. In combination with MK-2206, trastuzumab is administered by IV infusion at an initial dose of 8 mg/kg (loading dose) followed by 6 mg/kg q3wk.
Drug: MK-2206
[Part 1]: MK-2206 tablets will be given starting at a dose of 45 mg QOD and escalated to 60 mg QOD if tolerated, OR starting at a dose of 135 mg QW and escalated to 200 mg QW if tolerated. Dose reduction to 30mg QOD or 90 mg QW may be permitted. The dose of MK2206 will be increased or decreased as required to find the maximum tolerated dose (MTD) of MK2206 for both the QOD and QW dosing schedules in combination with trastuzumab. [Part 2] The Part 2 dosing level and schedule of MK2206 will be chosen from the MTD of either the QOD or QW dosing schedules depending on the toxicity profile and preliminary efficacy.
Biological: Trastuzumab
Trastuzumab will be administered as a 90-minute IV infusion at a loading dose of 8 mg/kg followed by 6 mg/kg q3wk.
Experimental: Pt. 2: MK-2206 (Pt.1 MTD) + Trastuzumab + Lapatinib 500mg, QD
Participants in Part 2 (Pt. 2) receive MK-2206 (dosed either QOD or QW) taken orally at the maximum tolerated dose defined in Part 1 (Pt. 1 MTD). MK-2206 is administered in combination with trastuzumab (IV infusion at an initial dose of 8 mg/kg (loading dose) followed by 6 mg/kg q3wk) as well as lapatinib 500 mg taken orally once daily (QD).
Drug: MK-2206
[Part 1]: MK-2206 tablets will be given starting at a dose of 45 mg QOD and escalated to 60 mg QOD if tolerated, OR starting at a dose of 135 mg QW and escalated to 200 mg QW if tolerated. Dose reduction to 30mg QOD or 90 mg QW may be permitted. The dose of MK2206 will be increased or decreased as required to find the maximum tolerated dose (MTD) of MK2206 for both the QOD and QW dosing schedules in combination with trastuzumab. [Part 2] The Part 2 dosing level and schedule of MK2206 will be chosen from the MTD of either the QOD or QW dosing schedules depending on the toxicity profile and preliminary efficacy.
Biological: Trastuzumab
Trastuzumab will be administered as a 90-minute IV infusion at a loading dose of 8 mg/kg followed by 6 mg/kg q3wk.
Drug: Lapatinib
Lapatinib tablets will be administered orally QD in doses of 500 mg, 750 mg, or 1000 mg.
Experimental: Pt. 2: MK-2206 (Pt.1 MTD) + Trastuzumab + Lapatinib 750mg, QD
Participants in Pt. 2 receive MK-2206 (dosed either QOD or QW) taken orally at the Pt. 1 MTD. MK-2206 is administered in combination with trastuzumab (IV infusion at an initial dose of 8 mg/kg (loading dose) followed by 6 mg/kg q3wk) as well as lapatinib 750 mg taken orally QD.
Drug: MK-2206
[Part 1]: MK-2206 tablets will be given starting at a dose of 45 mg QOD and escalated to 60 mg QOD if tolerated, OR starting at a dose of 135 mg QW and escalated to 200 mg QW if tolerated. Dose reduction to 30mg QOD or 90 mg QW may be permitted. The dose of MK2206 will be increased or decreased as required to find the maximum tolerated dose (MTD) of MK2206 for both the QOD and QW dosing schedules in combination with trastuzumab. [Part 2] The Part 2 dosing level and schedule of MK2206 will be chosen from the MTD of either the QOD or QW dosing schedules depending on the toxicity profile and preliminary efficacy.
Biological: Trastuzumab
Trastuzumab will be administered as a 90-minute IV infusion at a loading dose of 8 mg/kg followed by 6 mg/kg q3wk.
Drug: Lapatinib
Lapatinib tablets will be administered orally QD in doses of 500 mg, 750 mg, or 1000 mg.
Experimental: Pt. 2: MK-2206 (Pt.1 MTD) + Trastuzumab + Lapatinib 1000mg, QD
Participants in Part 2 (Pt. 2) receive MK-2206 (dosed either QOD or QW) taken orally at the Pt. 1 MTD. MK-2206 is administered in combination with trastuzumab (IV infusion at an initial dose of 8 mg/kg (loading dose) followed by 6 mg/kg q3wk) as well as lapatinib 1000 mg taken orally QD.
Drug: MK-2206
[Part 1]: MK-2206 tablets will be given starting at a dose of 45 mg QOD and escalated to 60 mg QOD if tolerated, OR starting at a dose of 135 mg QW and escalated to 200 mg QW if tolerated. Dose reduction to 30mg QOD or 90 mg QW may be permitted. The dose of MK2206 will be increased or decreased as required to find the maximum tolerated dose (MTD) of MK2206 for both the QOD and QW dosing schedules in combination with trastuzumab. [Part 2] The Part 2 dosing level and schedule of MK2206 will be chosen from the MTD of either the QOD or QW dosing schedules depending on the toxicity profile and preliminary efficacy.
Biological: Trastuzumab
Trastuzumab will be administered as a 90-minute IV infusion at a loading dose of 8 mg/kg followed by 6 mg/kg q3wk.
Drug: Lapatinib
Lapatinib tablets will be administered orally QD in doses of 500 mg, 750 mg, or 1000 mg.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants Experiencing ≥1 Adverse Event
Time Frame: Up to 36 weeks (up to 4 weeks following cessation of study treatment)
The number of participants experiencing an adverse event (AE) was assessed. An AE is 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. Further, any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the sponsor's product, is also an AE.
Up to 36 weeks (up to 4 weeks following cessation of study treatment)
Number of Participants Discontinuing Study Drug Due to an Adverse Event
Time Frame: Up to 32 weeks
The number of participants discontinuing study drug due to an AE was assessed. An AE is 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. Further, any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the sponsor's product, is also an AE.
Up to 32 weeks
Number of Participants Experiencing ≥1 Dose-Limiting Toxicity (DLT) in Cycle 1
Time Frame: Up to 3 weeks (up to day 21 of cycle 1)
A DLT is a drug-related AE not related to disease progression or intercurrent illnesses. Toxicities are graded in severity according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCICTCAE) version 3.0. The following are considered DLTs: A.) Hematologic [grade 4 neutropenia (≥5 days); grade 3/4 neutropenia; grade 4 thrombocytopenia.] B.) Non-Hematologic [any grade ≥3 non-hematologic toxicity except: grade 3 nausea, vomiting, diarrhea, or dehydration; asthenia; hypersensitivity; grade 3 elevated transaminases (1 week).] C.) Additional [any drug-related AE leading to MK-2206 dose modification; grade ≥2 drug-related AE causing drug interruption (≥8 days); any drug-related AE causing drug interruption (≥15 days); grade ≥3 glucose intolerance with grade ≥2 hyperglycemia; fasting glucose >250 mg/dL (≥2 days); grade ≥3 electrolyte abnormality; lactoacidosis or ketoacidosis; non-fasting grade 4 hyperglycemia; increased QTc interval; significant bradycardia.].
Up to 3 weeks (up to day 21 of cycle 1)
Maximum Tolerated Dose of MK-2206 in Combination With Trastuzumab (Part 1) and With Trastuzumab/Lapatinib (Part 2)
Time Frame: Up to 3 weeks (up to day 21 of cycle 1)
The maximum tolerated dose (MTD) of MK-2206 in combination with trastuzumab (Part 1) was assessed for both QOD and QW dosing schedules. To calculate MTD, a dose-response curve for the rate of patients in each treatment combination arm experiencing a DLT in Cycle 1 will be estimated using the pooling-of-adjacent-violators algorithm, with this dose-response curve used to determine the MTD. The MTD is defined as the dose at which the percentage of patients experiencing a DLT is the closest to 25% or 30% in Part 1 and Part 2, respectively. As the study was terminated prior to Part 2 enrollment, the MTD of MK-2206 in combination with trastuzumab/lapatinib could not be determined.
Up to 3 weeks (up to day 21 of cycle 1)
Recommended Phase 2 Dose of MK-2206 in Combination With Trastuzumab (Part 1) and With Trastuzumab/Lapatinib (Part 2)
Time Frame: Up to 36 weeks (up to 4 weeks following cessation of study treatment)
The recommended phase 2 dose (RP2D) of MK-2206 in combination with trastuzumab (Part 1) was assessed. Data from Part 1 informing the determination of the MTD (i.e. DLTs in cycle 1), along with safety and tolerability data, and the pharmacokinetic profile was used to determine the RP2D for both the QOD and QW dosing of MK-2206 in combination with trastuzumab. As the study was terminated prior to Part 2 enrollment, the RP2D of MK-2206 in combination with trastuzumab/lapatinib could not be determined.
Up to 36 weeks (up to 4 weeks following cessation of study treatment)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Merck Sharp & Dohme LLC

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 15, 2009

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 9, 2011

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 22, 2011

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 19, 2009

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 20, 2009

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 21, 2009

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 4, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 20, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2206-015
  • 2009_646
  • MK-2206-015 (Other Identifier: Merck Protocol Number)
  • 2009-012661-59 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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