A Phase 2 Study of LY2495655 in Participants With Pancreatic Cancer

Study Overview
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Brief Summary
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This phase 2 study is a multicenter, randomized, double-blind, placebo-controlled trial in participants with locally advanced/inoperable or metastatic pancreatic cancer, and will investigate 2 different doses of LY2495655 in combination with standard of care chemotherapy.

Official Title
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A Randomized Phase 2 Placebo-Controlled Study of LY2495655 in Patients With Advanced or Metastatic Pancreatic Cancer Receiving Chemotherapy

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: LY2495655
* Drug: Placebo
* Drug: Standard of Care Chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion: Unresectable or metastatic pancreas cancer; participants with previous radical surgery for pancreas cancer are eligible after progression is documented Participants may have received previous adjuvant treatment with gemcitabine with or without radiotherapy for pancreas cancer ECOG (Eastern Cooperative Oncology Group) Performance status ≤ 2 Adequate organ function Have an estimated life expectancy of at least 12 weeks and in the judgment of the investigator, will be able to complete at least 2 cycles of treatment Ability to perform the indicated functional performance measures at baseline Exclusion: Prior systemic therapy for unresectable/metastatic pancreas cancer Any medical or psychiatric condition, orthopedic or neuromuscular conditions that could limit participation or confound study results Currently taking medications that are considered both muscle building and performance enhancing (for example, androgen therapies, or anabolic steroids)

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: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 300 mg LY2495655 + chemotherapy<br>300 mg LY2495655 intravenous (IV) in combination with standard of care chemotherapy (investigator's choice) | Drug: LY2495655<br>* Intravenous (IV) treatment every 14 days while on study. Number of Cycles: until treatment options are exhausted or unacceptable toxicity develops.<br>Drug: Standard of Care Chemotherapy<br>* Standard of care, gemcitabine-based regimen (single-agent gemcitabine or gemcitabine plus erlotinib) or FOLFIRINOX (combination chemotherapy regimen including 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan). The choice of gemcitabine-based regimen or FOLFIRINOX will be determined by the investigator (based on the standard of care used at the treating institution or as directed by local regulatory authorities).<br>|
| Experimental: 100 mg LY2495655 + chemotherapy<br>100 mg LY2495655 intravenous (IV) in combination with standard of care chemotherapy (investigator's choice) | Drug: LY2495655<br>* Intravenous (IV) treatment every 14 days while on study. Number of Cycles: until treatment options are exhausted or unacceptable toxicity develops.<br>Drug: Standard of Care Chemotherapy<br>* Standard of care, gemcitabine-based regimen (single-agent gemcitabine or gemcitabine plus erlotinib) or FOLFIRINOX (combination chemotherapy regimen including 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan). The choice of gemcitabine-based regimen or FOLFIRINOX will be determined by the investigator (based on the standard of care used at the treating institution or as directed by local regulatory authorities).<br>|
| Placebo Comparator: Placebo + chemotherapy<br>Placebo in combination with standard of care chemotherapy (investigator's choice) | Drug: Placebo<br>* Intravenous (IV) treatment every 14 days while on study. Number of Cycles: until treatment options are exhausted or unacceptable toxicity develops.<br>Drug: Standard of Care Chemotherapy<br>* Standard of care, gemcitabine-based regimen (single-agent gemcitabine or gemcitabine plus erlotinib) or FOLFIRINOX (combination chemotherapy regimen including 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan). The choice of gemcitabine-based regimen or FOLFIRINOX will be determined by the investigator (based on the standard of care used at the treating institution or as directed by local regulatory authorities).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Overall survival (OS) duration was measured from the date of randomization to the date of death from any cause. | Baseline to Death from Any Cause (Up to 23 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | PFS was defined as the time from date of first dose to the first observation of disease progression or death from any cause. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST version 1.1) criteria. PD is ≥20% increase in sum of longest diameter of target lesions and/or a new lesion. | Baseline to Disease Progression or Death from Any Cause (Up to 16 months) | 
| Percentage of Participants With Tumor Response Rate (RR) | Response rate (RR) was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria. Complete Response (CR) was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter (mm) and normalization of tumor marker level of non-target lesions; Partial Response (PR) was defined as having at least a 30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD) was defined as having at least 20% increase in sum of longest diameter of target lesions and minimum 5 mm increase above nadir; Stable Disease (SD) was defined as small changes that did not meet above criteria. | Baseline to Disease Progression (Up to 11 months) | 
| Duration of Response | The duration of a complete response (CR) or partial response (PR) was defined as the time from first objective status assessment of CR or PR to the first time of progression or death as a result of any cause. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria. Complete Response (CR) was defined as the disappearance of all non-nodal target lesions, with the short axes of any target lymph nodes reduced to <10 millimeters (mm). Partial Response (PR) was defined as having at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph nodes), taking as reference the baseline sum diameter. | First CR or PR to Disease Progression (Up to 11 months) | 
| Change in Lean Body Mass | Change in lean body mass was assessed using dual-energy x-ray absorptiometry (DXA). | Baseline, Cycles 3, 5, 7, 9 and 11; Day 1 | 
| Change in Physical Performance Measures Using Hand Grip Strength | Hand grip strength (HGS) of the non-dominant hand measured using a hand dynamometer. | Baseline, Cycles 2, 4, 6, 8 and 10; Day 1 | 
| Change in Physical Performance Measures Using the Time Up and Go (TUG) Test | Time Up and Go (TUG) is a timed walking test designed to measure gait performance and balance. It measures in seconds the time taken by an individual to stand up from a standard arm chair (approximate seat height of 46 cm [18in], arm height 65 cm [25.6 in]), walk a distance of 3 meters (118 inches, approximately 10 feet), turn, walk back to the chair, and sit down. | Baseline, Cycles 2, 4, 6, 8 and 10; Day 1 | 
| Change in Physical Performance Measures Using the 6 Minute Walk Test | The 6 minute walk test measured the distance walked in 6 minutes, as quickly as possible, without running. | Baseline, Cycles 2, 4, 6, 8 and 10; Day 1 | 
| Change in Physical Performance Measures Using Stair Climbing Time (StC) | Stair climbing time (StC) measured the ascend and descend of a flight of 12 steps (each step 18 cm high and 28 cm deep). | Baseline, Cycles 3, 5, 7, 9 and 11; Day 1 | 
| Change in Patient Reported Outcomes (PRO) | Data from PRO scales are not be presented. An error in coding the scales (coded differently early and late in the study) occurred. Unable to determine which results were affected therefore analysis not completed. | Baseline, Cycles 2, 4, 6, 8 and 10; Day 1 | 
| Change in Pain Scale Physical Functioning | The 36-item Short-Form Health Survey (SF-36) pain scale is a generic, health-related scale assessing participant's quality of life on 8 domains: physical functioning, social functioning, bodily pain, vitality, mental health, role-physical, role-emotional and general health and 2 summary scores (mental component summary [MCS] and physical component summary [PCS]). The PCS physical functioning domain score ranges from 0 to 100 (higher scores indicate better health status). | Baseline, Cycles 2, 4, 6, 8 and 10; Day 1 | 
| Number of Participants With Anti-LY2495655 Antibodies |  | Cycle 1, Day 1 and Day 29 (Pre-Dose); Cycle 6 Day 1 |