A Dose-Escalation Study in Participants With Advanced Cancer

Phase 1

Completed

Conditions: Advanced Cancer

Interventions: Drug: LY2495655

Registration Number: NCT01524224

Lead Sponsor: Eli Lilly and Company

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

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 29

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 & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
LY2495655	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With One or More Drug-related Adverse Events	Baseline through End of Study (up to 51 months)	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.

Secondary Outcome Measures

Name	Time	Method
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
Pharmacokinetics (PK): Area Under the Concentration-time Curve From Time 0 to 336 Hours (AUC[0-336]) 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	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.

Trial Locations

Locations (1): 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.
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Vancouver, Washington, United States