Clinical trial NCT00848718: A Phase I Study of MK-2206 in Combination With Standard Chemotherapy in Participants With Locally Advanced or Metastatic Solid Tumors (MK-2206-003)
Official title: A Phase I Dose Escalation Study of MK-2206 in Combination With Standard Doses of Selected Chemotherapies or Targeted Agents in Patients With Locally Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Locally Advanced, Metastatic Solid Tumors
Keywords: Tumors, cancer
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2009-02-20
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1
timeFrame: Cycle 1 (Up to 21 days)
measure: Maximum Tolerated Dose (MTD) of MK-2206 Administered Every Other Day (QOD) in Combination With Carboplatin and Paclitaxel
timeFrame: Cycle 1 (Up to 21 days)
measure: MTD of MK-2206 Administered Every Three Weeks (Q3W) in Combination With Carboplatin and Paclitaxel
timeFrame: Cycle 1 (up to 21 days)
measure: MTD of MK-2206 Administered QOD in Combination With Docetaxel
timeFrame: Cycle 1 (up to 21 days)
measure: MTD of MK-2206 Administered Q3W in Combination With Docetaxel
timeFrame: Cycle 1 (up to 21 days)
measure: MTD of MK-2206 Administered QOD in Combination With Erlotinib
timeFrame: Cycle 1 (up to 21 days)
measure: MTD of MK-2206 Administered Once Every Week (QW) in Combination With Erlotinib
timeFrame: Cycle 1 (up to 21 days)
measure: Maximum Plasma Concentration of MK-2206 (Cmax)
timeFrame: At designated time points on Cycle 1 Day 1 (Up to 96 hours)
measure: Time to Maximum Plasma Concentration of MK-2206 (Tmax)
timeFrame: At designated time points on Cycle 1 Day 1 (Up to 96 hours)
measure: Minimum Plasma Concentration of MK-2206 (Ctrough)
timeFrame: At designated time points on Cycle 1 Day 1 (Up to 48 hours)
measure: Area Under the MK-2206 Concentration Versus Time Curve From Time Zero to 48 Hours Postdose (AUC 0-48h)
timeFrame: At designated time points on Cycle 1 Day 1 (Up to 48 hours)
Secondary outcomes:
measure: Number of Participants Who Had a Tumor Response of Complete Response (CR) or Partial Response (PR)
timeFrame: Up to approximately 4 months (6 cycles)
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Molife LR, Yan L, Vitfell-Rasmussen J, Zernhelt AM, Sullivan DM, Cassier PA, Chen E, Biondo A, Tetteh E, Siu LL, Patnaik A, Papadopoulos KP, de Bono JS, Tolcher AW, Minton S. Phase 1 trial of the oral AKT inhibitor MK-2206 plus carboplatin/paclitaxel, docetaxel, or erlotinib in patients with advanced solid tumors. J Hematol Oncol. 2014 Jan 3;7:1. doi: 10.1186/1756-8722-7-1.