Clinical trial NCT00670488: Dose Escalation Study With MK-2206 in Patients With Locally Advanced or Metastatic Solid Tumors (MK-2206-002)
Official title: A Phase I Dose Escalation Study of Oral MK-2206 in Patients With Locally Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Locally Advanced Tumors
Metastatic Solid Tumors
Cancer
Neoplasms
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2008-05-01
Enrollment: 104
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 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

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: Day 1 to Day 28 (Cycle 1)
measure: Number of Participants With One or More Adverse Events (AE)
timeFrame: Up to 269 days
measure: Area Under the Concentration-time Curve of MK-2206 From Time 0 to 48 Hours (AUC0-48hr) in Participants Receiving Multiple QOD Dosing
timeFrame: Days 1 and 27: predose and 0.5, 1, 2, 3, 4, 6, 10, 24, and 48 hours after MK-2206 dosing
measure: Maximum Concentration (Cmax) of MK-2206 in Participants Receiving Multiple QOD Dosing
timeFrame: Days 1 and 27: predose and 0.5, 1, 2, 3, 4, 6, 10, 24, and 48 hours after MK-2206 dosing
measure: Concentration of MK-2206 After 48 Hours (C48hr) in Participants Receiving Multiple QOD Dosing
timeFrame: Days 1 and 27: predose and 48 hours after MK-2206 dosing.
measure: Time to Maximum Concentration (Tmax) of MK-2206 in Participants Receiving Multiple QOD Dosing
timeFrame: Days 1 and 27: predose and 0.5, 1, 2, 3, 4, 6, 10, 24, and 48 hours after MK-2206 dosing
measure: Apparent Terminal Half-life (t½) of MK-2206 in Participants Receiving Multiple QOD Dosing
timeFrame: Day 27: predose and 0.5, 1, 2, 3, 4, 6, 10, 24, and 48 hours after MK-2206 dosing.
measure: AUC0-168hr in Participants Receiving Multiple QW Dosing
timeFrame: Days 1 and 22: predose and 2, 4, 6, 10, 24, 48, 96 hours, and 168 hours after MK-2206 dosing
measure: Cmax of MK-2206 in Participants Receiving Multiple QW Dosing
timeFrame: Days 1 and 22: predose and 2, 4, 6, 10, 24, 48, 96 hours, and 168 hours after MK-2206 dosing
measure: C48hr of MK-2206 in Participants Receiving Multiple QW Dosing
timeFrame: Days 1 and 22: predose and 48 hours after MK-2206 dosing
measure: Tmax of MK-2206 in Participants Receiving Multiple QW Dosing
timeFrame: Days 1 and 22: predose and 2, 4, 6, 10, 24, 48, 96 hours, and 168 hours after MK-2206 dosing
measure: t½ of MK-2206 in Participants Receiving Multiple QW Dosing
timeFrame: Day 22: predose and 2, 4, 6, 10, 24, 48, 96 hours, and 168 hours after MK-2206 dosing
Secondary outcomes:
measure: Phosphorylated Protein Kinase B (pAkt) Level on Cycle 1 Day 15 (C1D15) After Treatment With MK-2206 at the Maximum Tolerated Dose (MTD)
timeFrame: Baseline, Cycle 1 Day 15
measure: Number of Participants With Confirmed Response as Per Response Evaluation Criteria in Solid Tumors (RECIST)
timeFrame: From Cycle 1 Day 1 through the End of Study Visit (up to 6 months)
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: Yap TA, Yan L, Patnaik A, Fearen I, Olmos D, Papadopoulos K, Baird RD, Delgado L, Taylor A, Lupinacci L, Riisnaes R, Pope LL, Heaton SP, Thomas G, Garrett MD, Sullivan DM, de Bono JS, Tolcher AW. First-in-man clinical trial of the oral pan-AKT inhibitor MK-2206 in patients with advanced solid tumors. J Clin Oncol. 2011 Dec 10;29(35):4688-95. doi: 10.1200/JCO.2011.35.5263. Epub 2011 Oct 24.
citation: Yap TA, Yan L, Patnaik A, Tunariu N, Biondo A, Fearen I, Papadopoulos KP, Olmos D, Baird R, Delgado L, Tetteh E, Beckman RA, Lupinacci L, Riisnaes R, Decordova S, Heaton SP, Swales K, deSouza NM, Leach MO, Garrett MD, Sullivan DM, de Bono JS, Tolcher AW. Interrogating two schedules of the AKT inhibitor MK-2206 in patients with advanced solid tumors incorporating novel pharmacodynamic and functional imaging biomarkers. Clin Cancer Res. 2014 Nov 15;20(22):5672-85. doi: 10.1158/1078-0432.CCR-14-0868. Epub 2014 Sep 19.