A Study of LY2157299 in Participants With Pancreatic Cancer That is Advanced or Has Spread to Another Part of the Body

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the safety and side effects of LY2157299 in combination with gemcitabine in Japanese participants with pancreatic cancer that is advanced or has spread to another part of the body.

Official Title
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A Phase 1b Study of LY2157299 in Combination With Gemcitabine in Patients With Advanced or Metastatic Unresectable Pancreatic Cancer

Conditions
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Pancreatic Neoplasms

Intervention / Treatment
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* Drug: LY2157299
* Drug: Gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have histological or cytological diagnosis of adenocarcinoma of the pancreas that is locally advanced or metastatic and not amenable to resection with curative intent. These participants may have received prior chemotherapy, radiotherapy, cancer-related hormone therapy, or other investigational therapy as treatment or chemotherapy. Participants with previous radical surgery for pancreatic cancer are eligible after progression is documented. Have measurable disease or non-measurable disease, defined according to Response Evaluation Criteria in Solid Tumors (RECIST). Have given written informed consent prior to any study-specific procedures. Have adequate organ function. Have a performance status of less than or equal 1 on the Eastern Cooperative Oncology Group (ECOG). Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures. Prior radiation therapy for treatment of cancer is allowed to less than 25% of the bone marrow, and participants must have recovered from the acute toxic effects of their treatment prior to study enrollment. Prior radiation to the whole pelvis is not allowed. Males and females with reproductive potential: Must agree to use medically approved contraceptive precautions during the study and for 3 months following the last dose of study drug. Exclusion Criteria: Are currently enrolled in, or discontinued within the last 30 days of study enrollment, a clinical trial involving an investigational product or nonapproved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. Have moderate or severe cardiac disease: Myocardial infarction within 6 months prior to study enrollment, unstable angina pectoris, New York Heart Association (NYHA) Class III/IV congestive heart failure, or uncontrolled hypertension. Documented major electrocardiogram (ECG) abnormalities at the investigator's discretion. Major abnormalities documented by echocardiography with Doppler. Have significantly elevated brain natriuretic peptide (BNP) or elevated Troponin I at screening local laboratory tests. Predisposing conditions that are consistent with development of aneurysms of the ascending aorta or aortic stress. Have a history of cardiac or aortic surgery. Have known positive tests for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C virus antibodies (HCVAbs). Have symptomatic central nervous system (CNS) malignancy or metastasis. Are unable to swallow tablets or capsules. Are pregnant or breastfeeding. Have serious preexisting medical conditions as follows: Presence or history of interstitial pneumonitis. Uncontrollable severe diabetes. Presence of serious active infection or uncontrollable chronic infection. Presence of liver cirrhosis with Child-Pugh Stage of B or C. Other serious conditions judged by the investigator. Have previous or concurrent malignancy except for basal or squamous cell skin cancer (non-melanoma) and/or preinvasive carcinoma of the cervix, mucosal gastrointestinal or uterine carcinoma, or other solid tumors treated curatively and without evidence of recurrence for at least 3 years prior to enrollment. Have endocrine pancreatic tumors or ampullary cancer. Have current hematological malignancies. Have previously completed or withdrawn from this study or any other study investigating LY2157299. Have known allergies to LY2157299 or gemcitabine or any ingredient of LY2157299 or gemcitabine formulations. Are assessed as inadequate for the study by the investigator.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY2157299 + Gemcitabine<br>150 mg LY2157299 is administered orally twice daily for 14 days followed by 14 days without study drug (28 day cycle.) Gemcitabine 1000 milligram per square meter will be administered intravenously (IV) on Days 8, 15, and 22 in each cycle (28 day cycle). Participants may continue to receive treatment until discontinuation criteria are met. | Drug: LY2157299<br>* Administered orally<br>Drug: Gemcitabine<br>* Administered IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with LY2157299 Dose-Limiting Toxicities (DLT) |  | Cycle 1 (28 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of LY2157299 |  | Cycle 1: Predose on Day 1 through Day 28, Cycle 2 through last cycle: Predose on Day 1 (Cycle = 28 days; treatment estimated to last 4 cycles) | 
| PK: Area Under the Plasma Concentration Versus Time Curve (AUC) of LY2157299 |  | Cycle 1: Predose on Day 1 through Day 28, Cycle 2 through last cycle: Predose on Day 1 (Cycle = 28 days; treatment estimated to last 4 cycles) | 
| PK: Cmax of Gemcitabine |  | Cycle 1 (28 days): Predose on Day 8 through 2 hours after gemcitabine infusion on Day 8 | 
| PK: AUC of Gemcitabine |  | Cycle 1 (28 days): Predose on Day 8 through 2 hours after gemcitabine infusion on Day 8 | 
| Percentage of Participants with a Tumor Response |  | Baseline to study completion (estimated as 5 months) |