Pancreatic Cancer
Conditions
Brief summary
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.
Interventions
DRUGLY2495655
Intravenous (IV) treatment every 14 days while on study. Number of Cycles: until treatment options are exhausted or unacceptable toxicity develops.
DRUGPlacebo
Intravenous (IV) treatment every 14 days while on study. Number of Cycles: until treatment options are exhausted or unacceptable toxicity develops.
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).
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Baseline to Death from Any Cause (Up to 23 months) | Overall survival (OS) duration was measured from the date of randomization to the date of death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Tumor Response Rate (RR) | Baseline to Disease Progression (Up to 11 months) | 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. |
| Duration of Response | First CR or PR to Disease Progression (Up to 11 months) | 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. |
| Change in Lean Body Mass | Baseline, Cycles 3, 5, 7, 9 and 11; Day 1 | Change in lean body mass was assessed using dual-energy x-ray absorptiometry (DXA). |
| Change in Physical Performance Measures Using Hand Grip Strength | Baseline, Cycles 2, 4, 6, 8 and 10; Day 1 | Hand grip strength (HGS) of the non-dominant hand measured using a hand dynamometer. |
| Change in Physical Performance Measures Using the Time Up and Go (TUG) Test | Baseline, Cycles 2, 4, 6, 8 and 10; Day 1 | 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. |
| Progression Free Survival (PFS) | Baseline to Disease Progression or Death from Any Cause (Up to 16 months) | 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. |
| Change in Physical Performance Measures Using Stair Climbing Time (StC) | Baseline, Cycles 3, 5, 7, 9 and 11; Day 1 | Stair climbing time (StC) measured the ascend and descend of a flight of 12 steps (each step 18 cm high and 28 cm deep). |
| Change in Patient Reported Outcomes (PRO) | Baseline, Cycles 2, 4, 6, 8 and 10; Day 1 | 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. |
| Change in Pain Scale Physical Functioning | Baseline, Cycles 2, 4, 6, 8 and 10; Day 1 | 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). |
| Number of Participants With Anti-LY2495655 Antibodies | Cycle 1, Day 1 and Day 29 (Pre-Dose); Cycle 6 Day 1 | — |
| Change in Physical Performance Measures Using the 6 Minute Walk Test | Baseline, Cycles 2, 4, 6, 8 and 10; Day 1 | The 6 minute walk test measured the distance walked in 6 minutes, as quickly as possible, without running. |
Countries
Canada, Israel, Norway, United Kingdom, United States
Participant flow
Pre-assignment details
The reasons for discontinuation listed in the participant flow are the reasons the participant discontinued treatment and a participant was considered to have completed the trial if they died due to any cause while on study or completed treatment and was known to be alive at the last scheduled follow-up.
Participants by arm
| Arm | Count |
|---|---|
| 300 mg LY2495655 + Chemotherapy 300 mg LY2495655 intravenous (IV) in combination with standard of care chemotherapy (investigator's choice). | 41 |
| 100 mg LY2495655 + Chemotherapy 100 mg LY2495655 intravenous (IV) in combination with standard of care chemotherapy (investigator's choice). | 43 |
| Placebo + Chemotherapy Placebo in combination with standard of care chemotherapy (investigator's choice). | 41 |
| Total | 125 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 | 0 |
| Overall Study | Death | 7 | 6 | 5 |
| Overall Study | entry criteria not met | 0 | 1 | 0 |
| Overall Study | Physician Decision | 6 | 2 | 5 |
| Overall Study | Progressive Disease | 19 | 17 | 18 |
| Overall Study | Sponsor Decision | 1 | 8 | 7 |
| Overall Study | Withdrawal by Subject | 7 | 8 | 6 |
Baseline characteristics
| Characteristic | 300 mg LY2495655 + Chemotherapy | 100 mg LY2495655 + Chemotherapy | Placebo + Chemotherapy | Total |
|---|---|---|---|---|
| Age, Continuous | 65.0 years STANDARD_DEVIATION 11.3 | 67.4 years STANDARD_DEVIATION 10.7 | 68.4 years STANDARD_DEVIATION 9.1 | 66.9 years STANDARD_DEVIATION 10.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 3 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants | 19 Participants | 27 Participants | 66 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 21 Participants | 21 Participants | 14 Participants | 56 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 1 Participants | 5 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 38 Participants | 42 Participants | 35 Participants | 115 Participants |
| Sex: Female, Male Female | 16 Participants | 13 Participants | 15 Participants | 44 Participants |
| Sex: Female, Male Male | 25 Participants | 30 Participants | 26 Participants | 81 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 41 / 41 | 41 / 42 | 41 / 41 |
| serious Total, serious adverse events | 26 / 41 | 30 / 42 | 25 / 41 |
Outcome results
Primary
Overall Survival (OS)
Overall survival (OS) duration was measured from the date of randomization to the date of death from any cause.
Time frame: Baseline to Death from Any Cause (Up to 23 months)
Population: All randomized participants. Participants who were alive at data cut-off for the OS analysis or lost to follow-up were censored on the last date the participant was known to be alive. Censored participants; 300 mg LY2495655 = 9,100 mg LY2495655 =13, Placebo= 16.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 300 mg LY2495655 + Chemotherapy | Overall Survival (OS) | 8.02 months |
| 100 mg LY2495655 + Chemotherapy | Overall Survival (OS) | 9.82 months |
| Placebo + Chemotherapy | Overall Survival (OS) | 10.45 months |
Secondary
Change in Lean Body Mass
Change in lean body mass was assessed using dual-energy x-ray absorptiometry (DXA).
Time frame: Baseline, Cycles 3, 5, 7, 9 and 11; Day 1
Population: All participants that received at least one dose of study drug and had evaluable post-baseline measurements.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 300 mg LY2495655 + Chemotherapy | Change in Lean Body Mass | Baseline | 43742.92 grams (g) | Standard Deviation 10460.69 |
| 300 mg LY2495655 + Chemotherapy | Change in Lean Body Mass | Cycle 3 | 42629.79 grams (g) | Standard Deviation 10263.53 |
| 300 mg LY2495655 + Chemotherapy | Change in Lean Body Mass | Cycle 5 | 43121.85 grams (g) | Standard Deviation 11249.28 |
| 300 mg LY2495655 + Chemotherapy | Change in Lean Body Mass | Cycle 7 | 44407.02 grams (g) | Standard Deviation 11685.15 |
| 300 mg LY2495655 + Chemotherapy | Change in Lean Body Mass | Cycle 9 | 46879.22 grams (g) | Standard Deviation 12316.64 |
| 300 mg LY2495655 + Chemotherapy | Change in Lean Body Mass | Cycle 11 | 46155.53 grams (g) | Standard Deviation 9984.09 |
| 100 mg LY2495655 + Chemotherapy | Change in Lean Body Mass | Cycle 11 | 433316.42 grams (g) | Standard Deviation 11436.93 |
| 100 mg LY2495655 + Chemotherapy | Change in Lean Body Mass | Baseline | 44307.12 grams (g) | Standard Deviation 9853.15 |
| 100 mg LY2495655 + Chemotherapy | Change in Lean Body Mass | Cycle 7 | 45486.34 grams (g) | Standard Deviation 11424 |
| 100 mg LY2495655 + Chemotherapy | Change in Lean Body Mass | Cycle 9 | 43656.49 grams (g) | Standard Deviation 12335.08 |
| 100 mg LY2495655 + Chemotherapy | Change in Lean Body Mass | Cycle 3 | 44250.67 grams (g) | Standard Deviation 11600.33 |
| 100 mg LY2495655 + Chemotherapy | Change in Lean Body Mass | Cycle 5 | 45697.82 grams (g) | Standard Deviation 12035.96 |
| Placebo + Chemotherapy | Change in Lean Body Mass | Cycle 3 | 42282.45 grams (g) | Standard Deviation 8523.35 |
| Placebo + Chemotherapy | Change in Lean Body Mass | Cycle 5 | 43041.45 grams (g) | Standard Deviation 7649.44 |
| Placebo + Chemotherapy | Change in Lean Body Mass | Cycle 11 | 45667.63 grams (g) | Standard Deviation 8100.86 |
| Placebo + Chemotherapy | Change in Lean Body Mass | Cycle 7 | 45997.59 grams (g) | Standard Deviation 9429.5 |
| Placebo + Chemotherapy | Change in Lean Body Mass | Baseline | 42870.99 grams (g) | Standard Deviation 8971.73 |
| Placebo + Chemotherapy | Change in Lean Body Mass | Cycle 9 | 43405.26 grams (g) | Standard Deviation 7217.48 |
Secondary
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).
Time frame: Baseline, Cycles 2, 4, 6, 8 and 10; Day 1
Population: All randomized participants with evaluable SF-36 domain scores.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 300 mg LY2495655 + Chemotherapy | Change in Pain Scale Physical Functioning | Baseline | 6.62 units on a scale | Standard Deviation 2.23 |
| 300 mg LY2495655 + Chemotherapy | Change in Pain Scale Physical Functioning | Cycle 2 | 4.48 units on a scale | Standard Deviation 2.09 |
| 300 mg LY2495655 + Chemotherapy | Change in Pain Scale Physical Functioning | Cycle 4 | 5.33 units on a scale | Standard Deviation 1.91 |
| 300 mg LY2495655 + Chemotherapy | Change in Pain Scale Physical Functioning | Cycle 6 | 4.38 units on a scale | Standard Deviation 1.51 |
| 300 mg LY2495655 + Chemotherapy | Change in Pain Scale Physical Functioning | Cycle 8 | 4.14 units on a scale | Standard Deviation 1.46 |
| 300 mg LY2495655 + Chemotherapy | Change in Pain Scale Physical Functioning | Cycle 10 | 4.57 units on a scale | Standard Deviation 2.57 |
| 100 mg LY2495655 + Chemotherapy | Change in Pain Scale Physical Functioning | Cycle 10 | 5.58 units on a scale | Standard Deviation 2.87 |
| 100 mg LY2495655 + Chemotherapy | Change in Pain Scale Physical Functioning | Baseline | 6.81 units on a scale | Standard Deviation 2.55 |
| 100 mg LY2495655 + Chemotherapy | Change in Pain Scale Physical Functioning | Cycle 6 | 4.65 units on a scale | Standard Deviation 2.29 |
| 100 mg LY2495655 + Chemotherapy | Change in Pain Scale Physical Functioning | Cycle 8 | 5.85 units on a scale | Standard Deviation 2.44 |
| 100 mg LY2495655 + Chemotherapy | Change in Pain Scale Physical Functioning | Cycle 2 | 5.63 units on a scale | Standard Deviation 2.81 |
| 100 mg LY2495655 + Chemotherapy | Change in Pain Scale Physical Functioning | Cycle 4 | 4.78 units on a scale | Standard Deviation 2.02 |
| Placebo + Chemotherapy | Change in Pain Scale Physical Functioning | Cycle 2 | 5.04 units on a scale | Standard Deviation 2.03 |
| Placebo + Chemotherapy | Change in Pain Scale Physical Functioning | Cycle 4 | 4.83 units on a scale | Standard Deviation 2.5 |
| Placebo + Chemotherapy | Change in Pain Scale Physical Functioning | Cycle 10 | 3.55 units on a scale | Standard Deviation 1.92 |
| Placebo + Chemotherapy | Change in Pain Scale Physical Functioning | Cycle 6 | 4.25 units on a scale | Standard Deviation 1.91 |
| Placebo + Chemotherapy | Change in Pain Scale Physical Functioning | Baseline | 5.89 units on a scale | Standard Deviation 2.54 |
| Placebo + Chemotherapy | Change in Pain Scale Physical Functioning | Cycle 8 | 5.00 units on a scale | Standard Deviation 2.26 |
Secondary
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.
Time frame: Baseline, Cycles 2, 4, 6, 8 and 10; Day 1
Population: Zero participants analyzed. 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.
Secondary
Change in Physical Performance Measures Using Hand Grip Strength
Hand grip strength (HGS) of the non-dominant hand measured using a hand dynamometer.
Time frame: Baseline, Cycles 2, 4, 6, 8 and 10; Day 1
Population: All participants that received at least one dose of study drug and had evaluable post-baseline measurements.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 300 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using Hand Grip Strength | Cycle 4 | 25.56 kilogram (kg) | Standard Deviation 13.67 |
| 300 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using Hand Grip Strength | Cycle 10 | 25.13 kilogram (kg) | Standard Deviation 13.15 |
| 300 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using Hand Grip Strength | Cycle 6 | 26.58 kilogram (kg) | Standard Deviation 9.65 |
| 300 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using Hand Grip Strength | Cycle 2 | 25.90 kilogram (kg) | Standard Deviation 13.49 |
| 300 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using Hand Grip Strength | Baseline | 28.59 kilogram (kg) | Standard Deviation 11.99 |
| 300 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using Hand Grip Strength | Cycle 8 | 27.89 kilogram (kg) | Standard Deviation 11.46 |
| 100 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using Hand Grip Strength | Baseline | 29.00 kilogram (kg) | Standard Deviation 11.35 |
| 100 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using Hand Grip Strength | Cycle 2 | 26.70 kilogram (kg) | Standard Deviation 12.27 |
| 100 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using Hand Grip Strength | Cycle 4 | 24.47 kilogram (kg) | Standard Deviation 10.46 |
| 100 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using Hand Grip Strength | Cycle 6 | 26.32 kilogram (kg) | Standard Deviation 14.33 |
| 100 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using Hand Grip Strength | Cycle 8 | 26.22 kilogram (kg) | Standard Deviation 14.92 |
| 100 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using Hand Grip Strength | Cycle 10 | 29.23 kilogram (kg) | Standard Deviation 14.81 |
| Placebo + Chemotherapy | Change in Physical Performance Measures Using Hand Grip Strength | Cycle 2 | 25.26 kilogram (kg) | Standard Deviation 11.8 |
| Placebo + Chemotherapy | Change in Physical Performance Measures Using Hand Grip Strength | Cycle 10 | 33.27 kilogram (kg) | Standard Deviation 14.25 |
| Placebo + Chemotherapy | Change in Physical Performance Measures Using Hand Grip Strength | Cycle 8 | 25.44 kilogram (kg) | Standard Deviation 12.05 |
| Placebo + Chemotherapy | Change in Physical Performance Measures Using Hand Grip Strength | Cycle 4 | 28.02 kilogram (kg) | Standard Deviation 13.1 |
| Placebo + Chemotherapy | Change in Physical Performance Measures Using Hand Grip Strength | Baseline | 27.46 kilogram (kg) | Standard Deviation 12.54 |
| Placebo + Chemotherapy | Change in Physical Performance Measures Using Hand Grip Strength | Cycle 6 | 27.43 kilogram (kg) | Standard Deviation 14.01 |
Secondary
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).
Time frame: Baseline, Cycles 3, 5, 7, 9 and 11; Day 1
Population: All participants that received at least one dose of study drug and had evaluable post-baseline measurements.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 300 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using Stair Climbing Time (StC) | Cycle 9 | 217.82 joule/second | Standard Deviation 131.34 |
| 300 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using Stair Climbing Time (StC) | Cycle 5 | 230.23 joule/second | Standard Deviation 135.31 |
| 300 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using Stair Climbing Time (StC) | Cycle 11 | 193.24 joule/second | Standard Deviation 96.7 |
| 300 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using Stair Climbing Time (StC) | Baseline | 211.25 joule/second | Standard Deviation 129.57 |
| 300 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using Stair Climbing Time (StC) | Cycle 7 | 198.24 joule/second | Standard Deviation 83.19 |
| 300 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using Stair Climbing Time (StC) | Cycle 3 | 203.24 joule/second | Standard Deviation 113.76 |
| 100 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using Stair Climbing Time (StC) | Cycle 7 | 235.82 joule/second | Standard Deviation 111.95 |
| 100 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using Stair Climbing Time (StC) | Cycle 9 | 197.49 joule/second | Standard Deviation 102.51 |
| 100 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using Stair Climbing Time (StC) | Cycle 3 | 203.70 joule/second | Standard Deviation 87.82 |
| 100 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using Stair Climbing Time (StC) | Cycle 11 | 221.59 joule/second | Standard Deviation 107.49 |
| 100 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using Stair Climbing Time (StC) | Baseline | 206.92 joule/second | Standard Deviation 110.52 |
| 100 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using Stair Climbing Time (StC) | Cycle 5 | 211.99 joule/second | Standard Deviation 93 |
| Placebo + Chemotherapy | Change in Physical Performance Measures Using Stair Climbing Time (StC) | Cycle 11 | 188.78 joule/second | Standard Deviation 188.78 |
| Placebo + Chemotherapy | Change in Physical Performance Measures Using Stair Climbing Time (StC) | Baseline | 178.25 joule/second | Standard Deviation 65.18 |
| Placebo + Chemotherapy | Change in Physical Performance Measures Using Stair Climbing Time (StC) | Cycle 3 | 170.49 joule/second | Standard Deviation 76.52 |
| Placebo + Chemotherapy | Change in Physical Performance Measures Using Stair Climbing Time (StC) | Cycle 5 | 186.55 joule/second | Standard Deviation 95.2 |
| Placebo + Chemotherapy | Change in Physical Performance Measures Using Stair Climbing Time (StC) | Cycle 7 | 200.79 joule/second | Standard Deviation 130.74 |
| Placebo + Chemotherapy | Change in Physical Performance Measures Using Stair Climbing Time (StC) | Cycle 9 | 160.59 joule/second | Standard Deviation 87.6 |
Secondary
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.
Time frame: Baseline, Cycles 2, 4, 6, 8 and 10; Day 1
Population: All participants that received at least one dose of study drug and had evaluable post-baseline measurements.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 300 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using the 6 Minute Walk Test | Baseline | 351.49 meter | Standard Deviation 115.18 |
| 300 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using the 6 Minute Walk Test | Cycle 2 | 368.08 meter | Standard Deviation 137.65 |
| 300 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using the 6 Minute Walk Test | Cycle 4 | 379.90 meter | Standard Deviation 208.66 |
| 300 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using the 6 Minute Walk Test | Cycle 6 | 354.20 meter | Standard Deviation 104.74 |
| 300 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using the 6 Minute Walk Test | Cycle 8 | 365.00 meter | Standard Deviation 75.71 |
| 300 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using the 6 Minute Walk Test | Cycle 10 | 308.19 meter | Standard Deviation 57.23 |
| 100 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using the 6 Minute Walk Test | Cycle 10 | 372.15 meter | Standard Deviation 172.4 |
| 100 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using the 6 Minute Walk Test | Baseline | 382.49 meter | Standard Deviation 131.41 |
| 100 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using the 6 Minute Walk Test | Cycle 6 | 416.30 meter | Standard Deviation 102.49 |
| 100 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using the 6 Minute Walk Test | Cycle 8 | 347.32 meter | Standard Deviation 203.49 |
| 100 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using the 6 Minute Walk Test | Cycle 2 | 361.53 meter | Standard Deviation 143.7 |
| 100 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using the 6 Minute Walk Test | Cycle 4 | 323.79 meter | Standard Deviation 140.26 |
| Placebo + Chemotherapy | Change in Physical Performance Measures Using the 6 Minute Walk Test | Cycle 2 | 376.31 meter | Standard Deviation 107.25 |
| Placebo + Chemotherapy | Change in Physical Performance Measures Using the 6 Minute Walk Test | Cycle 4 | 386.48 meter | Standard Deviation 126.56 |
| Placebo + Chemotherapy | Change in Physical Performance Measures Using the 6 Minute Walk Test | Cycle 10 | 391.41 meter | Standard Deviation 143.18 |
| Placebo + Chemotherapy | Change in Physical Performance Measures Using the 6 Minute Walk Test | Cycle 6 | 376.45 meter | Standard Deviation 132.05 |
| Placebo + Chemotherapy | Change in Physical Performance Measures Using the 6 Minute Walk Test | Baseline | 381.62 meter | Standard Deviation 94.68 |
| Placebo + Chemotherapy | Change in Physical Performance Measures Using the 6 Minute Walk Test | Cycle 8 | 392.13 meter | Standard Deviation 113.43 |
Secondary
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.
Time frame: Baseline, Cycles 2, 4, 6, 8 and 10; Day 1
Population: All participants that received at least one dose of study drug and had evaluable post-baseline measurements.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 300 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using the Time Up and Go (TUG) Test | Baseline | 10.70 seconds | Standard Deviation 5.06 |
| 300 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using the Time Up and Go (TUG) Test | Cycle 2 | 9.19 seconds | Standard Deviation 2.6 |
| 300 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using the Time Up and Go (TUG) Test | Cycle 4 | 9.33 seconds | Standard Deviation 3.23 |
| 300 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using the Time Up and Go (TUG) Test | Cycle 6 | 10.14 seconds | Standard Deviation 2.02 |
| 300 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using the Time Up and Go (TUG) Test | Cycle 8 | 9.28 seconds | Standard Deviation 2.51 |
| 300 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using the Time Up and Go (TUG) Test | Cycle 10 | 10.56 seconds | Standard Deviation 1.4 |
| 100 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using the Time Up and Go (TUG) Test | Cycle 10 | 7.75 seconds | Standard Deviation 2.38 |
| 100 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using the Time Up and Go (TUG) Test | Baseline | 10.16 seconds | Standard Deviation 4.53 |
| 100 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using the Time Up and Go (TUG) Test | Cycle 6 | 8.84 seconds | Standard Deviation 2.94 |
| 100 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using the Time Up and Go (TUG) Test | Cycle 8 | 7.26 seconds | Standard Deviation 2.13 |
| 100 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using the Time Up and Go (TUG) Test | Cycle 2 | 10.15 seconds | Standard Deviation 3.93 |
| 100 mg LY2495655 + Chemotherapy | Change in Physical Performance Measures Using the Time Up and Go (TUG) Test | Cycle 4 | 12.19 seconds | Standard Deviation 8.96 |
| Placebo + Chemotherapy | Change in Physical Performance Measures Using the Time Up and Go (TUG) Test | Cycle 2 | 10.64 seconds | Standard Deviation 4.46 |
| Placebo + Chemotherapy | Change in Physical Performance Measures Using the Time Up and Go (TUG) Test | Cycle 4 | 9.18 seconds | Standard Deviation 2.6 |
| Placebo + Chemotherapy | Change in Physical Performance Measures Using the Time Up and Go (TUG) Test | Cycle 10 | 9.76 seconds | Standard Deviation 5.75 |
| Placebo + Chemotherapy | Change in Physical Performance Measures Using the Time Up and Go (TUG) Test | Cycle 6 | 9.77 seconds | Standard Deviation 3.96 |
| Placebo + Chemotherapy | Change in Physical Performance Measures Using the Time Up and Go (TUG) Test | Baseline | 10.04 seconds | Standard Deviation 4.04 |
| Placebo + Chemotherapy | Change in Physical Performance Measures Using the Time Up and Go (TUG) Test | Cycle 8 | 9.03 seconds | Standard Deviation 4.3 |
Secondary
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.
Time frame: First CR or PR to Disease Progression (Up to 11 months)
Population: All randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 300 mg LY2495655 + Chemotherapy | Duration of Response | 5.86 months |
| 100 mg LY2495655 + Chemotherapy | Duration of Response | 8.02 months |
| Placebo + Chemotherapy | Duration of Response | 9.20 months |
Secondary
Number of Participants With Anti-LY2495655 Antibodies
Time frame: Cycle 1, Day 1 and Day 29 (Pre-Dose); Cycle 6 Day 1
Population: All randomized participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 300 mg LY2495655 + Chemotherapy | Number of Participants With Anti-LY2495655 Antibodies | 0 Participants |
| 100 mg LY2495655 + Chemotherapy | Number of Participants With Anti-LY2495655 Antibodies | 1 Participants |
| Placebo + Chemotherapy | Number of Participants With Anti-LY2495655 Antibodies | 1 Participants |
Secondary
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.
Time frame: Baseline to Disease Progression (Up to 11 months)
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 300 mg LY2495655 + Chemotherapy | Percentage of Participants With Tumor Response Rate (RR) | 22 percentage of participants |
| 100 mg LY2495655 + Chemotherapy | Percentage of Participants With Tumor Response Rate (RR) | 25.6 percentage of participants |
| Placebo + Chemotherapy | Percentage of Participants With Tumor Response Rate (RR) | 26.8 percentage of participants |
Secondary
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.
Time frame: Baseline to Disease Progression or Death from Any Cause (Up to 16 months)
Population: All randomized participants.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 300 mg LY2495655 + Chemotherapy | Progression Free Survival (PFS) | 4.90 months |
| 100 mg LY2495655 + Chemotherapy | Progression Free Survival (PFS) | 6.87 months |
| Placebo + Chemotherapy | Progression Free Survival (PFS) | 8.21 months |