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

Sponsor
Merck Sharp & Dohme LLC
Study ID
NCT00963547
Phase
PHASE1
Status
Terminated

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • MK-2206 — DRUG
    \[Part 1\]: 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.
  • Trastuzumab — BIOLOGICAL
    Trastuzumab will be administered as a 90-minute IV infusion at a loading dose of 8 mg/kg followed by 6 mg/kg q3wk.
  • Lapatinib — DRUG
    Lapatinib tablets will be administered orally QD in doses of 500 mg, 750 mg, or 1000 mg.

Study Details

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.

Key Dates

Start date
Sep 15, 2009
Status verified
May 2024
Primary completion
Aug 9, 2011
Completion
Dec 22, 2011

Study Design

Enrollment
33 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • 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).
  • 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.
  • 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.
  • 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.
  • 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).
  • 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.
  • 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.

Primary Outcome Measure

Number of Participants Experiencing ≥1 Adverse Event [ Time Frame: Up to 36 weeks (up to 4 weeks following cessation of study treatment) ]

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