A Phase 2 Study of LY2495655 in Participants With Pancreatic Cancer

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

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.

Study Overview

• Status: Completed
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: LY2495655; Drug: Standard of Care Chemotherapy; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 125
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Ontario
    • Toronto, Ontario, Canada
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• Israel
  • Jerusalem, Israel
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Kfar Saba, Israel
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Petah Tiqva, Israel
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Tel Hashomer, Israel
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Tel-Aviv, Israel
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• Norway
  • Oslo, Norway
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Trondheim, Norway
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• United Kingdom
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • England
    • London, England, United Kingdom
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Hants
    • Southampton, Hants, United Kingdom
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • London
    • Acton, London, United Kingdom
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Nottinghamshire
    • Nottingham, Nottinghamshire, United Kingdom
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Scotland
    • Edinburgh, Scotland, United Kingdom
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • South Glamorgan
    • Cardiff, South Glamorgan, United Kingdom
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
• United States
  • District of Columbia
    • Washington, District of Columbia, United States
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Texas
    • Dallas, Texas, United States
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
    • The Woodlands, Texas, United States
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
    • Tyler, Texas, United States
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • Washington
    • Wenatchee, Washington, United States
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 300 mg LY2495655 + chemotherapy; 300 mg LY2495655 intravenous (IV) in combination with standard of care chemotherapy (investigator's choice)	Drug: LY2495655; Intravenous (IV) treatment every 14 days while on study. Number of Cycles: until treatment options are exhausted or unacceptable toxicity develops.; Drug: Standard of Care Chemotherapy; 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).
Experimental: 100 mg LY2495655 + chemotherapy; 100 mg LY2495655 intravenous (IV) in combination with standard of care chemotherapy (investigator's choice)	Drug: LY2495655; Intravenous (IV) treatment every 14 days while on study. Number of Cycles: until treatment options are exhausted or unacceptable toxicity develops.; Drug: Standard of Care Chemotherapy; 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).
Placebo Comparator: Placebo + chemotherapy; Placebo in combination with standard of care chemotherapy (investigator's choice)	Drug: Standard of Care Chemotherapy; 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).; Drug: Placebo; Intravenous (IV) treatment every 14 days while on study. Number of Cycles: until treatment options are exhausted or unacceptable toxicity develops.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: January 4, 2012
• First Submitted That Met QC Criteria: January 4, 2012
• First Posted (Estimate): January 6, 2012

Study Record Updates

• Last Update Posted (Actual): September 18, 2019
• Last Update Submitted That Met QC Criteria: September 6, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: 12552; I1Q-MC-JDDG (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• IPD Sharing Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)