This phase II trial studies how well selumetinib sulfate works in treating patients with pancreatic cancer with KRAS G12R mutations that has spread from where it started to nearby tissue or lymph nodes or other places in the body. Selumetinib sulfate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

NCT03040986

Conditions

1. KRAS NP_004976.2:p.G12R
2. Stage III Pancreatic Cancer AJCC v6 and v7
3. Stage IV Pancreatic Cancer AJCC v6 and v7

Interventions

1. Other: Laboratory Biomarker Analysis
2. Drug: Selumetinib Sulfate

MeSH:Pancreatic Neoplasms

HPO:Neoplasm of the pancreas

A Phase II Study of Selumetinib (AZD6244) for the Treatment of Advanced Pancreas Cancer Harboring KRAS G12R Mutations. --- G12R ---

Selumetinib Sulfate in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer With KRAS G12R Mutations This phase II trial studies how well selumetinib sulfate works in treating patients with pancreatic cancer with KRAS G12R mutations that has spread from where it started to nearby tissue or lymph nodes or other places in the body. --- G12R ---

Selumetinib Sulfate in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer With KRAS G12R Mutations This phase II trial studies how well selumetinib sulfate works in treating patients with pancreatic cancer with KRAS G12R mutations that has spread from where it started to nearby tissue or lymph nodes or other places in the body. --- G12R --- --- G12R ---

This will be a descriptive presentation only.. Inclusion Criteria: - Patients must have histologically confirmed locally advanced or metastatic pancreas cancer - Patients must have received at least 6 months fluorouracil (5-FU)- or gemcitabine-based treatments for pancreas cancer (fluorouracil, irinotecan hydrochloride, leucovorin calcium and oxaliplatin [FOLFIRINOX], fluorouracil, leucovorin calcium and oxaliplatin [FOLFOX], 5-FU+ nal-IRI [MM-398; nanoliposomal irinotecan], or 5-FU [including capecitabine], gemcitabine-based gemcitabine plus abraxane, gemcitabine monotherapy among others) - Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) with conventional techniques or as >= 10 mm (>= 1 cm) with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam - Patients must have Clinical Laboratory Improvement Act (CLIA) confirmed somatic KRAS G12R mutation as determined by sequence analysis of matched normal deoxyribonucleic acid (DNA) from any specimen obtained from the individual; patients must provide tumor sample for KRAS analysis or be willing to undergo mandatory screening biopsy - Patients must not have had chemotherapy, molecular therapy with erlotinib, radiation therapy, or experimental biological or molecular therapy for at least 4 weeks prior to starting study medication; patients who received FOLFIRINOX must be 6 weeks from the last administration of therapy; patients must have recovered from any acute toxicity related to prior therapy or surgery, to a grade 1 or less unless specified - Eastern Cooperative Oncology Group (ECOG) performance status =< 1 or Karnofsky >= 70% - Leukocytes >= 3,000/mcL - Absolute neutrophil count >= 1,500/mcL - Platelets >= 75,000/mcL - Hemoglobin (Hgb) >= 9.0 g/dL - Total bilirubin within normal institutional limits - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) < 3 x institutional upper limit of normal - Creatinine =< institutional upper limit of normal OR - Creatinine clearance > 60 mL/min/1.73 --- G12R ---

cetuximab, panitumumab) - Patients currently receiving any medication known to induce central serous chorioretinopathy which in the opinion of the principal investigator, would make the administration of study drug hazardous - Patients with active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment) - Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements - Any underlying medical condition which, in the opinion of the principal investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events - Patients who are receiving any other investigational agents - Patients with known brain metastases should be excluded from this clinical trial; no additional workup is needed to exclude brain metastases if the patient is asymptomatic or has no history of brain metastases - History of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD6244 or other agents used in study - Previous MEK, RAS, or RAF inhibitor use - Patients with the following cardiac conditions are excluded: - Uncontrolled hypertension (blood pressure [BP] of >= 150/95 despite medical support/management) - Acute coronary syndrome within 6 months prior to starting treatment - Uncontrolled angina - Canadian Cardiovascular Society grade II-IV despite medical support/management - Heart failure New York Heart Association (NYHA) class II or above - Prior or current cardiomyopathy (within 6 months) including but not limited to the following: - Known hypertrophic cardiomyopathy - Known arrhythmogenic right ventricular cardiomyopathy - Abnormal ejection fraction (echocardiogram [ECHO]) =< 53% (if a range is given then the upper value of the range will be used) or cardiac MRI - Previous moderate or severe impairment of left ventricular systolic function (left ventricular ejection fraction [LVEF] < 45% on echocardiography or equivalent on multi-gated acquisition scan [MUGA]) even if full recovery has occurred; echocardiogram (Echo) and additional cardiac studies not indicated unless clinically symptomatic or patient has significant cardiac history - Severe valvular heart disease - Atrial fibrillation with a ventricular rate > 100 beats per minute (bpm) on electrocardiogram (ECG) at rest - Fridericia's corrected QT interval (QTcF) >= 450 msec or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) are excluded; the use of medication(s) that can prolong QTc interval is prohibited while treated on this study - Patients with known ophthalmologic conditions, such as: - Current or past history of central serous retinopathy - Current or past history of retinal vein occlusion - Known intraocular pressure (IOP) > 21 mmHg (or upper limit of normal [ULN] adjusted by age) or uncontrolled glaucoma (irrespective of IOP); patients with controlled glaucoma and increased IOP who do not have meaningful vision (light perception only or no light perception) may be eligible after discussion with the study chair - Subjects with any other significant abnormality on ophthalmic examination (performed by an ophthalmologist) should be discussed with the study chair for potential eligibility - Ophthalmological findings secondary to long-standing optic pathway glioma (such as visual loss, optic nerve pallor or strabismus) or long-standing orbito-temporal plexiform neurofibroma (PN) (such as visual loss, strabismus) will NOT be considered a significant abnormality for the purposes of the study - Patients with refractory nausea and vomiting, chronic gastrointestinal (GI) diseases (e.g., inflammatory bowel disease) or significant bowel resection - Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible; HIV-positive patients not on antiviral therapy with undetectable viral loads and CD4 counts > 300, and after confirmation of eligibility after discussing with the study chair are eligible Inclusion Criteria: - Patients must have histologically confirmed locally advanced or metastatic pancreas cancer - Patients must have received at least 6 months fluorouracil (5-FU)- or gemcitabine-based treatments for pancreas cancer (fluorouracil, irinotecan hydrochloride, leucovorin calcium and oxaliplatin [FOLFIRINOX], fluorouracil, leucovorin calcium and oxaliplatin [FOLFOX], 5-FU+ nal-IRI [MM-398; nanoliposomal irinotecan], or 5-FU [including capecitabine], gemcitabine-based gemcitabine plus abraxane, gemcitabine monotherapy among others) - Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm (>= 2 cm) with conventional techniques or as >= 10 mm (>= 1 cm) with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam - Patients must have Clinical Laboratory Improvement Act (CLIA) confirmed somatic KRAS G12R mutation as determined by sequence analysis of matched normal deoxyribonucleic acid (DNA) from any specimen obtained from the individual; patients must provide tumor sample for KRAS analysis or be willing to undergo mandatory screening biopsy - Patients must not have had chemotherapy, molecular therapy with erlotinib, radiation therapy, or experimental biological or molecular therapy for at least 4 weeks prior to starting study medication; patients who received FOLFIRINOX must be 6 weeks from the last administration of therapy; patients must have recovered from any acute toxicity related to prior therapy or surgery, to a grade 1 or less unless specified - Eastern Cooperative Oncology Group (ECOG) performance status =< 1 or Karnofsky >= 70% - Leukocytes >= 3,000/mcL - Absolute neutrophil count >= 1,500/mcL - Platelets >= 75,000/mcL - Hemoglobin (Hgb) >= 9.0 g/dL - Total bilirubin within normal institutional limits - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) < 3 x institutional upper limit of normal - Creatinine =< institutional upper limit of normal OR - Creatinine clearance > 60 mL/min/1.73 --- G12R ---

cetuximab, panitumumab) - Patients currently receiving any medication known to induce central serous chorioretinopathy which in the opinion of the principal investigator, would make the administration of study drug hazardous - Patients with active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment) - Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements - Any underlying medical condition which, in the opinion of the principal investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events - Patients who are receiving any other investigational agents - Patients with known brain metastases should be excluded from this clinical trial; no additional workup is needed to exclude brain metastases if the patient is asymptomatic or has no history of brain metastases - History of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD6244 or other agents used in study - Previous MEK, RAS, or RAF inhibitor use - Patients with the following cardiac conditions are excluded: - Uncontrolled hypertension (blood pressure [BP] of >= 150/95 despite medical support/management) - Acute coronary syndrome within 6 months prior to starting treatment - Uncontrolled angina - Canadian Cardiovascular Society grade II-IV despite medical support/management - Heart failure New York Heart Association (NYHA) class II or above - Prior or current cardiomyopathy (within 6 months) including but not limited to the following: - Known hypertrophic cardiomyopathy - Known arrhythmogenic right ventricular cardiomyopathy - Abnormal ejection fraction (echocardiogram [ECHO]) =< 53% (if a range is given then the upper value of the range will be used) or cardiac MRI - Previous moderate or severe impairment of left ventricular systolic function (left ventricular ejection fraction [LVEF] < 45% on echocardiography or equivalent on multi-gated acquisition scan [MUGA]) even if full recovery has occurred; echocardiogram (Echo) and additional cardiac studies not indicated unless clinically symptomatic or patient has significant cardiac history - Severe valvular heart disease - Atrial fibrillation with a ventricular rate > 100 beats per minute (bpm) on electrocardiogram (ECG) at rest - Fridericia's corrected QT interval (QTcF) >= 450 msec or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) are excluded; the use of medication(s) that can prolong QTc interval is prohibited while treated on this study - Patients with known ophthalmologic conditions, such as: - Current or past history of central serous retinopathy - Current or past history of retinal vein occlusion - Known intraocular pressure (IOP) > 21 mmHg (or upper limit of normal [ULN] adjusted by age) or uncontrolled glaucoma (irrespective of IOP); patients with controlled glaucoma and increased IOP who do not have meaningful vision (light perception only or no light perception) may be eligible after discussion with the study chair - Subjects with any other significant abnormality on ophthalmic examination (performed by an ophthalmologist) should be discussed with the study chair for potential eligibility - Ophthalmological findings secondary to long-standing optic pathway glioma (such as visual loss, optic nerve pallor or strabismus) or long-standing orbito-temporal plexiform neurofibroma (PN) (such as visual loss, strabismus) will NOT be considered a significant abnormality for the purposes of the study - Patients with refractory nausea and vomiting, chronic gastrointestinal (GI) diseases (e.g., inflammatory bowel disease) or significant bowel resection - Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible; HIV-positive patients not on antiviral therapy with undetectable viral loads and CD4 counts > 300, and after confirmation of eligibility after discussing with the study chair are eligible KRAS NP_004976.2:p.G12R Stage III Pancreatic Cancer AJCC v6 and v7 Stage IV Pancreatic Cancer AJCC v6 and v7 Pancreatic Neoplasms PRIMARY OBJECTIVES: I. Determine the objective response rate to selumetinib sulfate (selumetinib) administered as 75 mg orally twice daily on a continuous schedule in patients with advanced pancreas cancer harboring KRAS G12R mutations. --- G12R ---

To determine the impact of additional genetic alterations on the response to selumetinib in pancreas cancer harboring KRAS G12R mutations. --- G12R ---

To develop a clinically applicable biomarker predicting response to selumetinib in pancreas cancer harboring KRAS G12R mutations. --- G12R ---

This research study is designed to evaluate the effects of a dendritic cell (kind of white blood cell) vaccine for pancreatic cancer.

NCT03592888

Conditions

1. Pancreatic Ductal Adenocarcinoma

Interventions

1. Drug: mDC3/8-KRAS Vaccine

MeSH:Adenocarcinoma

Inclusion Criteria: - Pathologically-confirmed KRAS(G12D-), KRAS(G12V-), KRAS(G12R-) or KRAS(G12C-mutated) pancreatic ductal adenocarcinoma who are at high risk of relapse and have no evidence of disease. --- G12D --- --- G12V --- --- G12R ---