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

Study at a glance

From the registry record, last updated by the sponsor on 4 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title

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

ClinicalTrials.gov ID

NCT00963547

Acronym / sponsor ID

2206-015

Conditions

Advanced Solid Tumors, Breast Cancer

Keywords

Documented to be HER2+

Phase

Phase 1

Study type

Interventional

Recruitment status

Terminated

Enrolment

33 participants (actual)

Lead sponsor

Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)

Study start

15 Sep 2009 (actual)

Primary completion

9 Aug 2011 (actual)

Study completion

22 Dec 2011 (actual)

First posted

21 Aug 2009 (estimated)

Results

Posted 31 Oct 2018

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

7

Who may qualify

Ages

18 years and older

Sex

All

Healthy volunteers

Not accepted

Age groups

Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Primary outcome

1. 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.

2. 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.

3. 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.].

4. 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.

5. 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.

Results and safety

Loading the posted results from ClinicalTrials.gov…

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2024.
• Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
• Results publication: PubMed 24252402Hudis C, Swanton C, Janjigian YY, Lee R, Sutherland S, Lehman R, Chandarlapaty S, Hamilton N, Gajria D, Knowles J, Shah J, Shannon K, Tetteh E, Sullivan DM, Moreno C, Yan L, Han HS. A phase 1 study evaluating the combination of an allosteric AKT inhibitor (MK-2206) and trastuzumab in patients with HER2-positive solid tumors. Breast Cancer Res. 2013 Nov 19;15(6):R110. doi: 10.1186/bcr3577.
• 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.