Selumetinib and Akt Inhibitor MK2206 or mFOLFOX Therapy Comprising Oxaliplatin and Fluorouracil in Treating Patients With Metastatic Pancreatic Cancer Previously Treated With Chemotherapy

Brief summary public domain (ClinicalTrials.gov)

This randomized phase II trial studies how well selumetinib and Akt inhibitor MK2206 work compared to modified fluorouracil, leucovorin calcium, and oxaliplatin (mFOLFOX) therapy in treating patients with metastatic pancreatic cancer previously treated with chemotherapy. Selumetinib and Akt inhibitor MK2206 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as oxaliplatin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet know whether selumetinib and Akt inhibitor MK2206 are more effective than oxaliplatin and fluorouracil in treating patients with metastatic pancreatic cancer.

Detailed description public domain (ClinicalTrials.gov)

PRIMARY OBJECTIVES: I. To assess overall survival in patients with metastatic pancreatic cancer treated with the combination of AZD6244 hydrogen sulfate (selumetinib) and MK-2206 (Akt inhibitor MK2206) compared to those treated with mFOLFOX. SECONDARY OBJECTIVES: I. To assess the frequency and severity of toxicity associated with the combination of AZD6244 hydrogen sulfate and MK-2206 compared to those with mFOLFOX in this patient population. TERTIARY OBJECTIVES: I. To assess progression free survival (PFS) in patients with metastatic pancreatic cancer treated with the combination of AZD6244 hydrogen sulfate and MK-2206 compared to those treated with mFOLFOX. II. To assess objective tumor response in the subset of patients with measurable disease (confirmed and unconfirmed complete and partial response) in patients with metastatic pancreatic cancer treated with the combination of AZD6244 hydrogen sulfate and MK-2206 compared to those treated with mFOLFOX. III. To bank tissue and blood for future translational medicine studies. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive oxaliplatin intravenously (IV) over 2 hours on days 1 and 15 and fluorouracil IV over 46-48 hours on days 1-2 and 15-16 (mFOLFOX). ARM II: Patients receive Akt inhibitor MK2206 orally (PO) on days 1, 8, 15, and 22, and selumetinib PO daily on days 1-28. In all arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months for up to 3 years.

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug [Up to 3 years]. Number, Participants. Abdominal pain: mFOLFOX (n=62): 1; MK2206 and Selumetinib (n=57): 0. Alanine aminotransferase increased: mFOLFOX (n=62): 0; MK2206 and Selumetinib (n=57): 4. Alkaline phosphatase increased: mFOLFOX (n=62): 0; MK2206 and Selumetinib (n=57): 2. Anemia: mFOLFOX (n=62): 2; MK2206 and Selumetinib (n=57): 3. Anorexia: mFOLFOX (n=62): 1; MK2206 and Selumetinib (n=57): 1. Aspartate aminotransferase increased: mFOLFOX (n=62): 0; MK2206 and Selumetinib (n=57): 3. Blood bilirubin increased: mFOLFOX (n=62): 1; MK2206 and Selumetinib (n=57): 0. Cognitive disturbance: mFOLFOX (n=62): 0; MK2206 and Selumetinib (n=57): 1. Dehydration: mFOLFOX (n=62): 1; MK2206 and Selumetinib (n=57): 6. Device related infection: mFOLFOX (n=62): 1; MK2206 and Selumetinib (n=57): 0. Diarrhea: mFOLFOX (n=62): 4; MK2206 and Selumetinib (n=57): 4. Edema face: mFOLFOX (n=62): 0; MK2206 and Selumetinib (n=57): 1. Encephalopathy: mFOLFOX (n=62): 0; MK2206 and Selumetinib (n=57): 1. Erythema multiforme: mFOLFOX (n=62): 0; MK2206 and Selumetinib (n=57): 1. Erythroderma: mFOLFOX (n=62): 0; MK2206 and Selumetinib (n=57): 1. Fatigue: mFOLFOX (n=62): 8; MK2206 and Selumetinib (n=57): 7. Generalized muscle weakness: mFOLFOX (n=62): 0; MK2206 and Selumetinib (n=57): 1. Hepatic failure: mFOLFOX (n=62): 0; MK2206 and Selumetinib (n=57): 1. Hyperglycemia: mFOLFOX (n=62): 1; MK2206 and Selumetinib (n=57): 7. Hypertension: mFOLFOX (n=62): 2; MK2206 and Selumetinib (n=57): 5. Hypokalemia: mFOLFOX (n=62): 1; MK2206 and Selumetinib (n=57): 1. Hypomagnesemia: mFOLFOX (n=62): 1; MK2206 and Selumetinib (n=57): 0. Hyponatremia: mFOLFOX (n=62): 1; MK2206 and Selumetinib (n=57): 4. Hypophosphatemia: mFOLFOX (n=62): 0; MK2206 and Selumetinib (n=57): 1. Hypotension: mFOLFOX (n=62): 1; MK2206 and Selumetinib (n=57): 1. Hypoxia: mFOLFOX (n=62): 0; MK2206 and Selumetinib (n=57): 1. Left ventricular systolic dysfunction: mFOLFOX (n=62): 0; MK2206 and Selumetinib (n=57): 1. Lung infection: mFOLFOX (n=62): 1; MK2206 and Selumetinib (n=57): 1. Lymphocyte count decreased: mFOLFOX (n=62): 8; MK2206 and Selumetinib (n=57): 0. Mucositis oral: mFOLFOX (n=62): 1; MK2206 and Selumetinib (n=57): 4. Multi-organ failure: mFOLFOX (n=62): 0; MK2206 and Selumetinib (n=57): 1. Nausea: mFOLFOX (n=62): 3; MK2206 and Selumetinib (n=57): 0. Neoplasms benign, malignant and unspecified: mFOLFOX (n=62): 0; MK2206 and Selumetinib (n=57): 2. Neutrophil count decreased: mFOLFOX (n=62): 4; MK2206 and Selumetinib (n=57): 0. Platelet count decreased: mFOLFOX (n=62): 1; MK2206 and Selumetinib (n=57): 0. Rash acneiform: mFOLFOX (n=62): 0; MK2206 and Selumetinib (n=57): 5. Rash maculo-papular: mFOLFOX (n=62): 0; MK2206 and Selumetinib (n=57): 7. Skin infection: mFOLFOX (n=62): 0; MK2206 and Selumetinib (n=57): 1. Soft tissue infection: mFOLFOX (n=62): 0; MK2206 and Selumetinib (n=57): 1. Stevens-Johnson syndrome: mF

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Overall Survival [Up to 3 years]. Median, months (95% Confidence Interval). mFOLFOX (n=62): 6.7 (6.0 to 8.3); MK2206 and Selumetinib (n=58): 3.9 (3.5 to 4.6). Analysis, mFOLFOX vs MK2206 and Selumetinib: p=0.15; Log Rank; superiority or other.