NCT01783171

Dinaciclib and Akt Inhibitor MK2206 in Treating Patients With Pancreatic Cancer That Cannot Be Removed by Surgery

A Phase I Trial of Dinaciclib (SCH727965) and MK-2206 in Metastatic Pancreatic Cancer With an Expansion Cohort in Advanced Pancreatic Cancer

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 42 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This randomized phase I trial studies the side effects and best dose of dinaciclib and Akt inhibitor MK2206 in treating patients with pancreatic cancer that cannot be removed by surgery. Dinaciclib and Akt inhibitor MK2206 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed description

PRIMARY OBJECTIVES: I. Determine the maximum tolerated dose (MTD), safety, and toxicity of the combination of MK-2206 (Akt inhibitor MK2206) and dinaciclib in patients with advanced pancreatic adenocarcinoma (Level 2.5, determined August 2015: Dinaciclib 9 mg/m2 intravenously \[IV\]; MK-2206 135 mg orally \[PO\]). SECONDARY OBJECTIVES: I. Assess the preliminary efficacy of the combination of MK-2206 and dinaciclib in metastatic pancreatic cancer patients as determined by disease control rate in an expansion cohort of patients at the MTD. II. Characterize the pharmacokinetic (PK) profile of the combination of MK-2206 and dinaciclib. III. Analyze pre-treatment tumor specimens for activation of retrovirus-associated deoxyribonucleic acid (DNA) sequence (RAS) downstream pathway signaling as potential predictors of treatment benefit. IV. Correlate post-treatment pharmacodynamic (PD) changes in phosphorylated extracellular signal-regulated kinase (p-ERK), phosphorylated-v-akt murine thymoma viral oncogene homolog 1 (p-AKT), p-ribosomal protein S6 kinase (S6), phosphorylated DNA-directed ribonucleic acid (RNA) polymerase II subunit RPB1 (pPOLR2), phosphorylated retinoblastoma protein (pRB), proliferation-related Ki-67 antigen (Ki-67), and cleaved caspase-3 in tumor biopsies and peripheral blood mononuclear cells with MK-2206 and dinaciclib exposure and treatment response to demonstrate proof-of-concept and assess for post-treatment predictive biomarkers. V. To assess the effect of polymorphic variations in candidate genes (cytochrome P450 3A4/5 \[CYP3A4/5\], ATP-binding cassette, sub-family B \[MDR/TAP\], member 1 \[ABCB1\]) and other genetic alterations that may be discovered during the conduct of the study, on MK-2206 and dinaciclib disposition, toxicity, and efficacy. OUTLINE: This is a dose-escalation study. Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive dinaciclib IV over 2 hours on day 1 of course 1. ARM B: Patients receive Akt inhibitor MK2206 PO on day 1 of course 1. After day 1, all patients receive Akt inhibitor MK2206 PO on days 1, 8, and 15 and dinaciclib IV over 2 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.

Conditions

• Pancreatic Adenocarcinoma
• Recurrent Pancreatic Carcinoma
• Stage III Pancreatic Cancer AJCC v6 and v7
• Stage IV Pancreatic Cancer AJCC v6 and v7
• Unresectable Pancreatic Carcinoma

Interventions

Type	Name	Description
DRUG	Akt Inhibitor MK2206	Given PO
DRUG	Dinaciclib	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
OTHER	Pharmacological Study	Correlative studies

Timeline

• Start date: 2013-01-15
• Primary completion: 2016-07-12
• Completion: 2016-07-12
• First posted: 2013-02-04
• Last updated: 2017-08-22

Locations

5 sites across 2 countries: United States, Canada