Pancreatic Cancer
Conditions
Brief summary
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.
Interventions
DRUGLY2090314
LY2090314 administered IV
DRUGFOLFOX
FOLFOX administered IV
DRUGGemcitabine
Gemcitabine administered IV
DRUGNab-paclitaxel
Nab-paclitaxel administered IV
Sponsors
Mayo Clinic
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to 4 Hours Post-Treatment on Day 0 in Glycogen Synthase Phosphorylation | Baseline, 4 Hours Post-Treatment on Day 0 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Baseline to Disease Progression Up to 18 Months | PFS was as the time from enrollment to the earliest documented evidence of disease progression or death,whatever comes first. |
| Percentage of Participants Who Survived at 6 Months | Baseline to Date of Death to any cause Up to 6 Months | — |
| Overall Survival (OS) | Baseline to Date of Death Due to any Cause Up to 21 Months | — |
| Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Overall Response Rate (ORR)] | Baseline Up to 6 Months | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| LY2090314 + Gemcitabine 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/m²) gemcitabine given IV on days 1, 8 and 15. Cohort closed to new enrollment per protocol addendum. | 3 |
| LY2090314 + FOLFOX 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. | 10 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Protocol Violation | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | LY2090314 + Gemcitabine | Total | LY2090314 + FOLFOX |
|---|---|---|---|
| Age, Continuous | 60.7 years STANDARD_DEVIATION 8.5 | 63.2 years STANDARD_DEVIATION 5.7 | 64.0 years STANDARD_DEVIATION 4.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 11 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 3 Participants | 12 Participants | 9 Participants |
| Region of Enrollment United States | 3 participants | 13 participants | 10 participants |
| Sex: Female, Male Female | 1 Participants | 5 Participants | 4 Participants |
| Sex: Female, Male Male | 2 Participants | 8 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 3 | 10 / 10 |
| serious Total, serious adverse events | 3 / 3 | 7 / 10 |
Outcome results
Primary
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.
Time frame: Baseline, 4 Hours Post-Treatment on Day 0
Population: Zero participants analyzed. GSK3β phosphorylation levels were not determined, and the primary endpoint was not examined as there wasn't viable tumor tissue for analysis.
Secondary
Overall Survival (OS)
Time frame: Baseline to Date of Death Due to any Cause Up to 21 Months
Population: All the participants that received at least one dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LY2090314 + Gemcitabine | Overall Survival (OS) | 1.8 Months |
| LY2090314 + FOLFOX | Overall Survival (OS) | 7.7 Months |
Secondary
Percentage of Participants Who Survived at 6 Months
Time frame: Baseline to Date of Death to any cause Up to 6 Months
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LY2090314 + Gemcitabine | Percentage of Participants Who Survived at 6 Months | 0 Percentage of participants |
| LY2090314 + FOLFOX | Percentage of Participants Who Survived at 6 Months | 50.0 Percentage of participants |
Secondary
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.
Time frame: Baseline Up to 6 Months
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LY2090314 + Gemcitabine | Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Overall Response Rate (ORR)] | 0 Percentage of Participants |
| LY2090314 + FOLFOX | Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Overall Response Rate (ORR)] | 10.0 Percentage of Participants |
Secondary
Progression Free Survival (PFS)
PFS was as the time from enrollment to the earliest documented evidence of disease progression or death,whatever comes first.
Time frame: Baseline to Disease Progression Up to 18 Months
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LY2090314 + Gemcitabine | Progression Free Survival (PFS) | 1.8 Months |
| LY2090314 + FOLFOX | Progression Free Survival (PFS) | 3.4 Months |