A Study of MK2206 in Combination With Trastuzumab and Lapatinib for the Treatment of HER2+ Solid Tumors (2206-015)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00963547
Recruitment Status : Completed
First Posted : August 21, 2009
Last Update Posted : February 4, 2015
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
This study will find the maximum tolerated dose of MK2206 in combination with both trastuzumab and trastuzumab/lapatinib in patients with HER2+ breast cancer and other solid tumors.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Breast Cancer Drug: MK2206 Drug: Comparator: MK2206 Biological: Comparator: trastuzumab Drug: Comparator: lapatinib Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 31 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Investigation of the Combination of MK2206, Trastuzumab and Lapatinib in HER2+ Solid Tumors
Study Start Date : September 2009
Actual Primary Completion Date : August 2011
Actual Study Completion Date : December 2011

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: 1
Part 1: MK2206 + trastuzumab
Drug: MK2206
Part 1: MK2206 tablets will be given starting at a dose of 45 mg every other day and escalated to 60 mg if tolerated OR starting at a dose of 135 mg weekly and escalated to 200 mg weekly if tolerated. Dose reduction to 30mg every other day or 90 mg weekly may be permitted. The dose of MK2206 will be increased or decreased as required to find the maximum tolerated dose of MK2206 for both the every other day and weekly dosing schedules in combination with trastuzumab. The Part 2 dosing level and schedule of MK2206 will be chosen from the maximum tolerated dose of either the every other day or weekly dosing schedules depending on the toxicity profile and preliminary efficacy.

Biological: Comparator: trastuzumab
Trastuzumab will be administered as a 90-minute intravenous infusion at a loading dose of 8 mg/kg followed by 6 mg/kg every 3 weeks.

Experimental: 2
Part 2: MK2206 + trastuzumab + lapatinib
Drug: Comparator: MK2206
Part 2: The maximum tolerated dose of MK2206 determined in Part 1 will be administered in combination with trastuzumab and lapatinib to determine the maximum tolerated dose of the three-drug combination.

Biological: Comparator: trastuzumab
Trastuzumab will be administered as a 90-minute intravenous infusion at a loading dose of 8 mg/kg followed by 6 mg/kg every 3 weeks.

Drug: Comparator: lapatinib
Lapatinib tablets will be administered orally in doses of 500 mg, 750 mg, or 1000 mg.

Primary Outcome Measures :
  1. Incidence of Dose-Limiting Toxicities (DLTs) and Maximum tolerated dose (MTD) of MK2206 in combination with Trastuzumab and Trastuzumab/Lapatinib [ Time Frame: 21 Days ]
  2. Characterize safety and tolerability of MK2206 by monitoring incidence rate of adverse experiences [ Time Frame: study duration ]
  3. Recommended Phase 2 Dose of MK2206 in Combination with Trastuzumab and Trastuzumab/Lapatinib [ Time Frame: study duration ]

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patient has a histologically or cytologically-confirmed locally advanced or metastatic HER2+ solid tumor
  • Female patients have a negative pregnancy test
  • Patient is able to swallow tablets

Exclusion Criteria:

  • Patient has had chemotherapy, radiotherapy or biological therapy within 4 weeks of screening. Patients who were receiving trastuzumab and/or lapatinib prior to screening must be off both medications for 1 week prior to first dose of MK2206 if trastuzumab had been administered at 2 mg/kg weekly and 3 weeks if trastuzumab had been administered at 6 mg/kg weekly
  • Patient has primary CNS tumor or known active CNS metastases
  • Patient has a history or evidence of heart disease
  • Patient has poorly controlled high blood pressure or diabetes
  • Patient is pregnant or breastfeeding or is expecting to conceive or father children during the study
  • Patient is HIV positive

Publications of Results:
Responsible Party: Merck Sharp & Dohme Corp. Identifier: NCT00963547     History of Changes
Other Study ID Numbers: 2206-015
First Posted: August 21, 2009    Key Record Dates
Last Update Posted: February 4, 2015
Last Verified: February 2015

Keywords provided by Merck Sharp & Dohme Corp.:
Documented to be HER2+

Additional relevant MeSH terms:
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action