A Study of LY2090314 and Chemotherapy in Participants With Metastatic Pancreatic Cancer

Study Overview
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Brief Summary
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Purpose of this phase I/II study is to test how well LY2090314 works in combination with different chemotherapies in treating participants with metastatic pancreatic cancer.

Official Title
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Phase I/II Study of LY2090314 and Chemotherapy in Metastatic Pancreatic Cancer Patients With Metastases Amenable to Biopsy

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: LY2090314
* Drug: FOLFOX
* Drug: Gemcitabine
* Drug: Nab-paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Metastatic pancreatic cancer with metastases amenable to biopsy Willingness to provide tissue and blood samples for research purposes Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1 Exclusion Criteria: History of islet cell, acinar cell, or cystadenocarcinomas Prior cytotoxic chemotherapy for metastatic disease, except prior gemcitabine or FOLFIRINOX (5FU + leucovorin + irinotecan + oxaliplatin) Radiation therapy, immunotherapy or biologic therapy <28 days prior to study entry

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY2090314 + Gemcitabine<br>LY2090314 given intravenously (IV) on days 1 (at cycle 1 LY2090314 given on day 0 instead of day 1), 8 and 15 in 28 day cycle in combination with 1000 milligram/square meter (mg/m^2) gemcitabine given IV on days 1, 8 and 15. Cohort closed to new enrollment per protocol addendum. | Drug: LY2090314<br>* LY2090314 administered IV<br>Drug: Gemcitabine<br>* Gemcitabine administered IV<br>* Other names: LY188011;|
| Experimental: LY2090314 + FOLFOX<br>LY2090314 given IV on days 1 (at cycle 1 LY2090314 given on day 0 instead of day 1), and 15 in 28 day cycle in combination with FOLFOX (leucovorin + 5-fluorouracil + oxaliplatin) given IV, on days 1 and 15 in 28 day cycle. | Drug: LY2090314<br>* LY2090314 administered IV<br>Drug: FOLFOX<br>* FOLFOX administered IV<br>* Other names: FOLFOX (leucovorin + 5-fluorouracil + oxaliplatin);|
| Experimental: LY2090314 + Gemcitabine + Nab-paclitaxel<br>LY2090314 given IV on days 1 (at cycle 1 LY2090314 given on day 0 instead of day 1), 8 and 15 in 28 day cycle in combination with 1000 mg/m^2 gemcitabine + 125 mg/m^2 nab-paclitaxel given IV on days 1, 8 and 15 in 28-day cycle. New cohort opened per protocol amendment. | Drug: LY2090314<br>* LY2090314 administered IV<br>Drug: Gemcitabine<br>* Gemcitabine administered IV<br>* Other names: LY188011;Drug: Nab-paclitaxel<br>* Nab-paclitaxel administered IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to 4 Hours Post-Treatment on Day 0 in Glycogen Synthase Phosphorylation | Change in the phosphorylation level of glycogen synthase, a glycogen synthase kinase-3 beta (GSK-3beta) inhibitor, from baseline to 4 hours post-treatment on day 0 using tumor tissue and blood specimens. | Baseline, 4 Hours Post-Treatment on Day 0 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) |  | Baseline to Date of Death Due to any Cause Up to 21 Months | 
| Percentage of Participants Who Survived at 6 Months |  | Baseline to Date of Death to any cause Up to 6 Months | 
| Progression Free Survival (PFS) | PFS was as the time from enrollment to the earliest documented evidence of disease progression or death,whatever comes first. | Baseline to Disease Progression Up to 18 Months | 
| Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Overall Response Rate (ORR)] | Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST v1.1) criteria. CR was defined as the disappearance of all target and non-target lesions and all target and non-target lymph nodes were non-pathological or normal in size [<10 millimeter (mm) short axis]. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions taking as reference the baseline sum diameters. ORR calculated as: (sum of the number of participants with PRs and CRs) divided by (number of evaluable participants) multiplied by 100. A CR or PR noted as the objective status on 2 consecutive evaluations at least 4 weeks apart. | Baseline Up to 6 Months |