A Dose-Escalation Study in Participants With Advanced Cancer

A Phase 1 Dose-Escalation Study of LY2495655, an Anti-Myostatin Monoclonal Antibody, in Patients With Advanced Cancer

This study is a multicenter, open-label, dose-escalation phase 1 study of intravenous (IV) LY2495655 in participants with advanced cancer.

Study Overview

• Status: Completed
• Conditions: Advanced Cancer
• Intervention / Treatment: Drug: LY2495655

Detailed Description

This study will consist of the following parts:

1. Dose Escalation - Cohorts of at least 3 participants will be treated with increasing doses of LY2475655 until maximum tolerated dose (MTD) criteria are met in 1 of the 6 dose levels, or the 6th cohort is completed without meeting maximum tolerated dose criteria.
2. Dose Confirmation - Up to 10 more participants will be enrolled to the MTD dose level, or if it was not possible to define the MTD during dose escalation, all clinical and bioanalytical data will be reviewed to select the recommended Phase 2 dose and an up to 10 additional participants will be enrolled to this dose level.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85260
      • 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.
  • New York
    • New York, New York, United States, 10032
      • 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.
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • 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, 75246
      • 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, 77380
      • 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, 75702
      • 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
    • Vancouver, Washington, United States, 98684
      • 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: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the trial and for 3 months following the last dose of study drug
• Females with child bearing potential must have had a negative serum pregnancy test less than or equal to 7 days prior to the first dose of study drug
• Have an estimated life expectancy of greater than 12 weeks
• Have a histological or cytological diagnosis of cancer (with the exception of breast or prostate cancer) that is advanced and/or metastatic, for which no proven effective therapy exists or the participant has declined anticancer therapy OR
• Have a histological or cytological diagnosis of metastatic breast or metastatic prostate cancer and receiving stable anti-hormone therapy for at least 2 months
• Have adequate hematologic, hepatic, and renal function
• Have a performance status of less than or equal to 2 on the Eastern Cooperative Oncology Group (ECOG) scale
• Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, or any other investigational therapy, for at least 30 days (6 weeks for mitomycin-C or nitrosoureas) prior to study enrollment and have recovered from the acute effects of therapy. Participants receiving anti-hormone therapy as specified in criteria above are not excluded

Exclusion Criteria:

• Have received treatment within 30 days of the initial dose of study drug with a drug that has not received regulatory approval for any indication
• Have serious preexisting medical conditions other than their cancer (at the discretion of the investigator)
• Have central nervous system malignancy or metastasis (screening not required)
• Have a history of severe chronic diseases that could interfere with either strength evaluation or body mass assessment during participation in this study including, but not limited to, ischemic disease (affecting the heart, brain, or extremities), uncontrolled hypertension, uncontrolled pain, severe chronic obstructive pulmonary disease, uncompensated heart failure (New York Heart Association Class III or IV), uncontrolled diabetes, or liver cirrhosis (Child-Pugh Class C)
• Have a history of inherited or acquired neuromuscular diseases including multiple sclerosis, muscular dystrophies, or myasthenia gravis
• Have active systemic inflammatory conditions including rheumatoid arthritis, dermatomyositis, severe arthrosis, or scleroderma
• Have unstable bone lesions, or any bone instability, fusion, arthroplasty, tendon repair, synovectomy, and so on, due to any of the before-mentioned conditions or due to accident that could interfere with completion of the physical tests in this protocol
• Have chronic glucocorticosteroid use greater than 10 mg of prednisone per day or equivalent
• Have known positive test results for hepatitis B surface antigen (HBSAg), or hepatitis C antibodies (HCAb). Screening is not required
• Have untreated hypothyroidism or hyperthyroidism
• Have history of seizures, convulsions (except previous febrile convulsions), or stroke
• Present with evidence of major depressive disorder, or history of obsessive compulsive disorder, significant psychiatric disease such as schizophrenia, bipolar disorder, or delirium
• Have depressive symptoms associated with their cancer that require treatment with any of the excluded drugs listed in protocol
• Have a previous history of discontinuation of a monoclonal antibody therapy due to allergy or severe infusion reaction
• Are scheduled to start or already receive any anti-cancer hormone treatments for breast or prostate cancer in the adjuvant or neoadjuvant setting

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: LY2495655; Administered intravenously (IV) every 2 weeks (14 days) for four (4) 14 day cycles. Participants receiving clinical benefit may continue to receive treatment until one or more of the discontinuation criteria are met. Starting dose in Part 1 (dose escalation) will be 2 mg. The dose will be subsequently increased to 7 mg, 21 mg, 70 mg, 210 mg, and 700 mg. The dose administered in Part 2 (dose confirmation) will be determined from Part 1.

Drug: LY2495655; administered intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With One or More Drug-related Adverse Events	A summary of other non-serious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section. An AE is summarized if the onset date is on or after the first dose of study drug and within 30 days after the last dose, or it occurred before the first dose of study drug and worsened while on the therapy.	Baseline through End of Study (up to 51 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK): Area Under the Concentration-time Curve From Time 0 to 336 Hours (AUC[0-336]) of LY2495655	AUC(0-336h) is the area under the drug concentration versus time curve within a dosing interval (0-336 hours). Due to the small number per cohort (participants dropping out) calculations of the accumulation factor of exposure for repeated every-other-week dosing were based on simulated area under the drug concentration versus time curve within a dosing interval (AUCτ) instead of observed values. The 90-percentage confidence interval was calculated as the predictive interval.	Cycle 1 and Cycle 4 Days 1 (pre-dose, end of infusion, 2hr, 6hr, 10-12hr after the infusion ends) and Day 2, 3, 5, 8
Pharmacokinetics: Maximum Concentration (Cmax) of LY2495655		Cycle 1 and Cycle 4 Days 1 (pre-dose, end of infusion, 2hr, 6hr, 10-12hr after the infusion ends) and Day 2, 3, 5, 8

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: January 30, 2012
• First Submitted That Met QC Criteria: January 30, 2012
• First Posted (Estimate): February 1, 2012

Study Record Updates

• Last Update Posted (Actual): April 1, 2019
• Last Update Submitted That Met QC Criteria: January 4, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Advanced Cancer; Metastatic Cancer; Neoplasm; Metastases
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: 11207 (Registry Identifier: DAIDS ES Registry Number); I1Q-MC-JDDB (Other Identifier: Eli Lilly and Company)