A Study for Participants With Advanced Cancer

A Phase I Study of LY2523355 in Patients With Advanced Cancer

This study is being conducted to determine the safety of LY2523355 for the treatment of advanced and/or metastatic cancer (including Non-Hodgkin's lymphoma).

Study Overview

• Status: Completed
• Conditions: Metastatic Cancer; Advanced Cancer
• Intervention / Treatment: Drug: LY2523355; Drug: LY2523355; Drug: pegfilgrastim

Detailed Description

This study is a multi-center, non-randomized, open label, dose-escalation, Phase 1 study of intravenous LY2523355 in participants with advanced and/or metastatic cancer (including Non-Hodgkin's Lymphoma) for whom no treatment of higher priority exists.

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • 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.
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • 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 Criteria:

• Have a diagnosis of advanced and/or metastatic cancer (solid tumors or Non-Hodgkin's lymphoma) that is refractory to standard therapy or for which no proven effective therapy exists. Participants entering Part B of the study must also have a tumor that is safely amenable to serial biopsies
• Have the presence of measurable or nonmeasurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST, Therasse et al. 2000) or Revised International Working Group Lymphoma Response Criteria (Cheson et al. 2007)
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
• Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, cancer-related hormonal therapy, or other investigational therapy for at least 28 days (6 weeks for mitomycin-C or nitrosoureas) prior to study enrollment
• 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 urine or 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 or equal to 12 weeks

Exclusion Criteria:

• Have symptomatic, untreated or uncontrolled central nervous system (CNS) metastases. Participants with treated CNS metastases are eligible provided their disease is radiographically stable, asymptomatic, and they are not currently receiving corticosteroids and/or anticonvulsants. Screening of asymptomatic participants without history of CNS metastases is not required
• Have current acute or chronic leukemia
• Have had an autologous or allogenic bone marrow transplant
• Have the following conduction abnormalities: PR >250 milliseconds (msec), second degree or complete atrioventricular (AV) block, intraventricular conduction delay (IVCD) with QRS ≥120 msec, left branch bundle block (LBBB), right branch bundle block (RBBB), Wolf-Parkinson- White syndrome (WPW), left anterior fascicular block (LAFB), left posterior fascicular block (LPFB), or other conduction abnormality that in the opinion of the investigator would preclude safe participation in this study.
• Females who are pregnant or lactating
• Known hypersensitivity to pegfilgrastim or filgrastim

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LY2523355	Drug: LY2523355; Administered intravenously as a 1-hour infusion on Days 1, 2, 3 of each 21-day cycle for at least 2 cycles. Participants may continue on study drug until disease progression, unacceptable toxicity or other withdrawal criterion is met. Starting dose for LY2523355 alone arm is 0.125 milligrams per meter square per day (mg/m²/day).; Drug: LY2523355; Administered intravenously as a 1-hour infusion on Days 1, 2, 3 of each 21-day cycle for at least 2 cycles. Participants may continue on study drug until disease progression, unacceptable toxicity or other withdrawal criterion is met. Starting dose for LY2523355 + pegfilgrastim is 4 mg/m²/day.
Experimental: LY2523355 + pegfilgrastim	Drug: LY2523355; Administered intravenously as a 1-hour infusion on Days 1, 2, 3 of each 21-day cycle for at least 2 cycles. Participants may continue on study drug until disease progression, unacceptable toxicity or other withdrawal criterion is met. Starting dose for LY2523355 alone arm is 0.125 milligrams per meter square per day (mg/m²/day).; Drug: LY2523355; Administered intravenously as a 1-hour infusion on Days 1, 2, 3 of each 21-day cycle for at least 2 cycles. Participants may continue on study drug until disease progression, unacceptable toxicity or other withdrawal criterion is met. Starting dose for LY2523355 + pegfilgrastim is 4 mg/m²/day.; Drug: pegfilgrastim; 6 milligrams (mg) administered subcutaneously on Day 4 of each 21-day cycle for the 2 planned cycles and for any subsequent cycles of LY2523355 received.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recommended Dose for Phase 2 Studies	Recommended Phase 2 dose was determined by the maximum tolerated dose (MTD). The MTD was defined as the dose that caused <1/3 of all participants treated with the study drug to experience a dose-limiting toxicity (DLT). A DLT was defined as an adverse event (AE) occurring during Cycle 1 that fulfilled 1 of the following criteria: Any Common Terminology Criteria for Adverse Events (CTCAE), version (v) 3.0 Grade ≥3 nonhematological toxicity possibly or likely related to the study drug (except for nausea/vomiting/diarrhea without maximal symptomatic/prophylactic treatment); any CTCAE v 3.0 Grade ≥3 thrombocytopenia with bleeding; any CTCAE v3.0 Grade 4 hematological toxicity of >5 days duration; any febrile neutropenia.	Baseline, daily up to 21 days in Cycle 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Clinically Significant Effects	Adverse events (AEs) were considered clinically significant effects. Data presented are the number of participants who experienced serious AEs (SAEs), other non-serious AEs and deaths during the study, including the 30-day follow-up. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.	Baseline to study completion including 30-day follow-up up to 647 days,any AE reported
Pharmacokinetics: Maximum Plasma Concentration (Cmax) of LY2523355 Following A Single Dose	Cmax following a single dose of LY2523355 at each dose level in the presence or absence of pegfilgrastim.	Cycle 1 Day 1(21-day cycle):End of infusion (EOI), Day 2: Predose, EOI, Day 3: Predose, EOI, between 1-2 hour EOI, Day 4: anytime, Day 8:anytime, Day 9: anytime, Day 10: anytime
Pharmacokinetics: Plasma Cmax of LY2523355 Following Multiple Doses	Cmax following multiple doses of LY2523355 at each dose level in the presence or absence of pegfilgrastim.	Cycle 1, Day 3(21-day cycle): End of infusion
Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity [AUC(0-∞)] of LY2523355 Following A Single Dose	AUC(0-∞) following a single dose of LY2523355 at each dose level in the presence or absence of pegfilgrastim.	Cycle 1,Day 1(21-day cycle): End of infusion (EOI), Day 2: Predose, EOI, Day 3: Predose, EOI, between 1-2 hour EOI, Day 4: anytime, Day 8:anytime, Day 9: anytime, Day 10: anytime
Pharmacokinetics: AUC(0-∞) of LY2523355 Following Multiple Doses	AUC(0-∞) following multiple doses of LY2523355 at each dose level in the presence or absence of pegfilgrastim.	Cycle 1, Day 3(21-day cycle): End of infusion
Number of Participants With Tumor Response	Data presented are the number of participants with a confirmed complete response (CR) or partial response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. CR is the disappearance of all target and non-target lesions. PR is a ≥30% decrease in sum of longest diameter of target lesions without new lesion and progression of non-target lesions.	Baseline to measured disease progression or discontinuation up to 617 days

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): May 1, 2012

Study Registration Dates

• First Submitted: October 1, 2010
• First Submitted That Met QC Criteria: October 4, 2010
• First Posted (Estimate): October 5, 2010

Study Record Updates

• Last Update Posted (Actual): August 6, 2018
• Last Update Submitted That Met QC Criteria: August 3, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Cancer; Advanced Cancer; Metastatic Cancer
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplastic Processes; Neoplasms; Neoplasm Metastasis
• Other Study ID Numbers: 11618; I1Y-MC-JFBA (Other Identifier: Eli Lilly and Company)