Phase 1
N=104
Dose Escalation Study With MK-2206 in Patients With Locally Advanced or Metastatic Solid Tumors (MK-2206-002)
Locally Advanced Tumors · Metastatic Solid Tumors · Cancer · Neoplasms
Bottom Line
View on ClinicalTrials.gov: NCT00670488 ↗Enrolled (actual)
104
Serious AEs
40.4%
Results posted
Apr 2019
Primary outcome: Primary: Number of Participants With Dose Limiting Toxicities (DLTs) — 0; 1; 0; 0 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- MK-2206 (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Merck Sharp & Dohme LLC
- Primary completion
- Jul 2011
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Dose Limiting Toxicities (DLTs) |
0; 1; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With One or More Adverse Events (AE) |
3; 58; 3; 7; 3; 5 | — |
| PRIMARY Area Under the Concentration-time Curve of MK-2206 From Time 0 to 48 Hours (AUC0-48hr) in Participants Receiving Multiple QOD Dosing |
916; 1950; 2110; 3950; NA; 6160 | — |
| PRIMARY Maximum Concentration (Cmax) of MK-2206 in Participants Receiving Multiple QOD Dosing |
33.7; 71.6; 102; 132; NA; 176 | — |
| PRIMARY Concentration of MK-2206 After 48 Hours (C48hr) in Participants Receiving Multiple QOD Dosing |
14.1; 30.9; 30.6; 64.1; 67.9; 100 | — |
| PRIMARY Time to Maximum Concentration (Tmax) of MK-2206 in Participants Receiving Multiple QOD Dosing |
6.0; 4.0; 6.0; 6.0; 4.0; 6.0 | — |
| PRIMARY Apparent Terminal Half-life (t½) of MK-2206 in Participants Receiving Multiple QOD Dosing |
62.7; 66.3; 66.2; 65.6 | — |
| PRIMARY AUC0-168hr in Participants Receiving Multiple QW Dosing |
6510; 12000; 16400; 27700; 14000; 20700 | — |
| PRIMARY Cmax of MK-2206 in Participants Receiving Multiple QW Dosing |
81.7; 199; 264; 466; 231; 337 | — |
| PRIMARY C48hr of MK-2206 in Participants Receiving Multiple QW Dosing |
50.9; 90.3; 121; 253; 103; 155 | — |
| PRIMARY Tmax of MK-2206 in Participants Receiving Multiple QW Dosing |
6.0; 4.0; 6.0; 4.0; 6.0; 7.0 | — |
| PRIMARY t½ of MK-2206 in Participants Receiving Multiple QW Dosing |
71.6; 88.9; 75.1; 53.7; 64.4 | — |
| SECONDARY Phosphorylated Protein Kinase B (pAkt) Level on Cycle 1 Day 15 (C1D15) After Treatment With MK-2206 at the Maximum Tolerated Dose (MTD) |
2.15; 0.29 | — |
| SECONDARY Number of Participants With Confirmed Response as Per Response Evaluation Criteria in Solid Tumors (RECIST) |
0; 0; 0; 0; 0; 0 | — |
Summary
The primary purpose of this study is to investigate the Dose Limiting Toxicities (DLTs), pharmacokinetics (PK), and pharmacodynamics (PD) of MK-2206 administered orally to participants with advanced solid tumors. The preliminary efficacy of MK-2206 will also be investigated.
Eligibility Criteria
Inclusion Criteria
- Participant must have confirmed locally advanced or metastatic solid tumors that have failed to respond to standard therapy, have gotten worse or have come back after existing therapy
- Has normal organ function; is no greater than 2 on the ECOG Performance Scale
- Has a negative blood or urine pregnancy test within 72 hours of receiving the first dose of study drug if participant is female
- Is able to swallow capsules and has no surgical or bodily condition that will prevent the patient from swallowing and absorbing oral medications on an ongoing basis
Exclusion Criteria
- Participant has had chemotherapy, radiotherapy, biological therapy or surgery within 4 weeks of starting the study and has not recovered from adverse events caused by the treatment
- Is currently participating or has participated in a study with an investigational compound or device within 30 days
- Has a primary central nervous system tumor
- Has a history or current evidence of heart disease, slow heart rate or untreated high blood pressure
- Is a known diabetic who is taking insulin or oral antidiabetic therapy
- Is pregnant or breastfeeding or planning to become pregnant during the study
- Is HIV-positive
- Has known history of Hepatitis B or C or active Hepatitis A
- Is receiving treatment with oral corticosteroids
Data sourced from ClinicalTrials.gov (NCT00670488). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.