Phase 1
N=77
A Phase I Study of MK-2206 in Combination With Standard Chemotherapy in Participants With Locally Advanced or Metastatic Solid Tumors (MK-2206-003)
Locally Advanced, Metastatic Solid Tumors
Bottom Line
View on ClinicalTrials.gov: NCT00848718 ↗Enrolled (actual)
77
Serious AEs
61.1%
Results posted
Nov 2019
Primary outcome: Primary: Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1 — 1; 2; 1; 1 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- MK-2206 (Drug); docetaxel (Drug); erlotinib (Drug); carboplatin (Drug); paclitaxel (Drug); corticosteroid (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Merck Sharp & Dohme LLC
- Primary completion
- May 2011
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1 |
1; 2; 1; 1; 2; 3 | — |
| PRIMARY Maximum Tolerated Dose (MTD) of MK-2206 Administered Every Other Day (QOD) in Combination With Carboplatin and Paclitaxel |
NA | — |
| PRIMARY MTD of MK-2206 Administered Every Three Weeks (Q3W) in Combination With Carboplatin and Paclitaxel |
NA | — |
| PRIMARY MTD of MK-2206 Administered QOD in Combination With Docetaxel |
NA | — |
| PRIMARY MTD of MK-2206 Administered Q3W in Combination With Docetaxel |
NA | — |
| PRIMARY MTD of MK-2206 Administered QOD in Combination With Erlotinib |
NA | — |
| PRIMARY MTD of MK-2206 Administered Once Every Week (QW) in Combination With Erlotinib |
NA | — |
| PRIMARY Maximum Plasma Concentration of MK-2206 (Cmax) |
57.7; 88.3; 144; 247; 431; 42.9 | — |
| PRIMARY Time to Maximum Plasma Concentration of MK-2206 (Tmax) |
4.0; 8.0; 6.0; 10.0; 5.0; 6.0 | — |
| PRIMARY Minimum Plasma Concentration of MK-2206 (Ctrough) |
24.9; 40.6; 1.36; 4.67; 2.21; 17.1 | — |
| PRIMARY Area Under the MK-2206 Concentration Versus Time Curve From Time Zero to 48 Hours Postdose (AUC 0-48h) |
1630; 2700; 4130; 7420; 9730; 1320 | — |
| SECONDARY Number of Participants Who Had a Tumor Response of Complete Response (CR) or Partial Response (PR) |
1; 3; 0; 1; 1; 0 | — |
Summary
The purpose of this study is to compare the safety and tolerability of several dose levels of MK-2206 in combination with chemotherapy and targeted therapy agents in participants with locally advanced or metastatic solid tumors.
The primary hypotheses are that administration of MK-2206 in combination with either carboplatin + paclitaxel, docetaxel, or erlotinib in participants with locally advanced or metastatic solid tumors will have acceptable tolerability, a dose limiting toxicity (DLT) rate of ≤30%, plasma exposure and pharmacodynamics that exceed target thresholds, and allow for definition of a maximum tolerated dose (MTD) in each of the 3 combinations.
Eligibility Criteria
Inclusion Criteria
- Participants must have locally advanced or metastatic solid tumors.
- Participant is male or female greater than or equal to 18 years of age.
- Participant must have a performance status less than or equal to 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
- Female participants of childbearing potential has a negative serum or urine pregnancy test within 72 hours prior to receiving the first dose of study medication.
- Participants in the MK-2206 + carboplatin/paclitaxel and MK-2206 + docetaxel treatment arms will be limited to no more than 3 prior cytotoxic therapies for metastatic or recurrent diseases.
- Participant is able to swallow capsules and has no surgical or anatomical condition that will prevent the Participant from swallowing.
Exclusion Criteria
- Participant has had chemotherapy, radiotherapy or biological therapy within 4 weeks.
- Participants must be least 4 weeks post-surgery and do not expect major surgery in the study duration.
- Participant is currently participating or has participated in a study with an investigational compound or device within 30 days.
- Participant has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- Participant with a primary central nervous system tumor.
- Participant has known hypersensitivity to the components of study drug.
- Participant has a history or current evidence of heart disease.
- Participant has evidence of clinically significant bradycardia (slow heart rate).
- Participant has uncontrolled high blood pressure.
- Participant at significant risk for hypokalemia (low potassium levels).
- Participant is a known diabetic
- Participant has known psychiatric or substance abuse disorders.
- Participant is a user of illicit drugs.
- Participant is pregnant or breastfeeding.
- Participant is Human Immunodeficiency Virus (HIV) positive.
- Participant has known history of Hepatitis B or C or active Hepatitis A.
- Participant has symptomatic ascites or pleural effusion.
- Participant is receiving treatment with oral corticosteroids.
- Participant is using a potent cytochrome P(450) 3A4 (CYP3A4) inhibitor or inducer.
Data sourced from ClinicalTrials.gov (NCT00848718). 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.