A Study of LY2584702 in Solid Tumors

A Phase 1 Study of LY2584702 in Japanese Patients With Solid Tumors

The purpose of this study is to assess the safety and tolerability of LY2584702 in Japanese patients with advanced and/or metastatic solid tumors for which no proven effective therapy exists.

Study Overview

• Status: Completed
• Conditions: Cancer
• Intervention / Treatment: Drug: LY2584702

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Chiba, Japan
    • 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: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Have histological or cytological evidence of a diagnosis of advanced and/or metastatic cancer (solid tumors) that is refractory to standard therapy and/or therapies known to provide clinical benefit, or for which no standard therapy exists.
• Have the presence of disease amenable to efficacy assessment as defined by the Response Evaluation Criteria In Solid Tumors (RECIST). Japanese patients who have advanced non-measurable disease with elevation of a validated tumor marker may be eligible, if discussed and agreed upon by the investigator and Lilly.

• Have adequate organ function including:

  • Hematologic: Absolute neutrophil count (ANC) greater than or equal to 1.5 x 10^9/liter (L), platelets greater than or equal to 100 x 10^9/L, and hemoglobin greater than or equal to 9 gram/deciliter (g/dL) (transfusions are not allowed prior to enrollment within 2 weeks).
  • Hepatic: Bilirubin less than or equal to 1.5 times upper limit of normal (ULN), alkaline phosphatase (ALP), alanine transaminase (ALT) and aspartate transaminase (AST) less than or equal to 2.5 times ULN, or 5 times ULN for patients with hepatic metastases. Patients with bone metastases may enter with alkaline phosphatase values less than 5 times ULN, as long as other hepatic parameters meet inclusion criteria.
  • Renal: Serum creatinine less than or equal to 1.5 times ULN.
• Have a performance status of less than or equal to 2 on the Eastern Cooperative Oncology Group scale
• Have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, cancer-related hormonal therapy prior to study enrollment and recovered from the acute effects of therapy.
• Have an estimated life expectancy of 12 weeks or greater
• Are able to swallow capsules

Exclusion Criteria:

• Have received treatment within 4 weeks of the initial dose of study drug with a drug that has not received regulatory approval for any indication.
• Have serious preexisting medical conditions or serious concomitant systemic disorders that, in the opinion of the investigator, would preclude participation in this study.
• Prior clinical history of tuberculosis (patient doubt tuberculosis is screening required), and positive test results in hepatitis B surface antigen (HBSAg), or hepatitis C antibodies (HCAb) (screening required).
• Have symptomatic central nervous system (CNS) malignancy or metastasis. Patients 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 patients without history of CNS metastasis is not required.
• Have hematologic malignancies, or lymphoma.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LY2584702	Drug: LY2584702; Dose escalation starting at 50 milligram (mg). On Day 1, subjects will receive a single oral dose. After a two-day observation period, subjects will receive oral doses twice daily for a 28-day cycle. Patients may continue 28-day cycles of twice daily dosing until discontinuation criteria are met.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Clinically Significant Effects	A clinically significant effect was any event that was a dose-limiting toxicity event (DLT). DLT was defined as an adverse event related to LY2584702 during Cycle 1 (Day 1 to Day 30) that fulfills any one of the following criteria; Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or 4 non-hematological toxicity; platelet count <50.0 x 10^9/Liter (L) with bleeding; CTCAE Grade 4 platelet count decreased; neutrophil count <0.5 x 10^9/L lasting for 5 days or longer; any febrile neutropenia; CTCAE Grade 4 anemia; participant risk due to increasing toxicity.	Baseline through 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Tumor Response	Tumor response was assessed according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1. Complete Response (CR) is disappearance of all target lesions; Partial Response (PR) is ≥30% decrease in sum of longest diameter of target lesions.	Baseline to study completion up to Day 183
Pharmacokinetics: Area Under the Concentration Time Curve (AUC) of LY2584702	AUC of single dose is AUC(0-12hours), and AUC of multiple doses is AUC during one dosing interval at steady state.	Cycle 1 Day 1: Predose, 0.5,1,2,3,5,8,12 hours; Cycle 1 Day 2:24 and 36 hours; Cycle 1 Day 3: Predose sample (before first dose on day 3); Cycle 1 Day 10: Predose,0.5,1,2,3,5,8,12 hours;Cycle 1 Day 17: Predose;Cycle 1 Day24: Predose;Cycle 2 Day 1: Predose
Pharmacokinetics: Maximum Concentration (Cmax) of LY2584702		Cycle 1 Day 1: Predose, 0.5,1,2,3,5,8,12 hours; Cycle 1 Day 2:24 and 36 hours; Cycle 1 Day 3: Predose sample (before first dose on day 3); Cycle 1 Day 10: Predose,0.5,1,2,3,5,8,12 hours;Cycle 1 Day 17: Predose;Cycle 1 Day24: Predose;Cycle 2 Day 1: Predose

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): November 1, 2011
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: November 12, 2010
• First Submitted That Met QC Criteria: November 15, 2010
• First Posted (Estimate): November 16, 2010

Study Record Updates

• Last Update Posted (Actual): August 21, 2018
• Last Update Submitted That Met QC Criteria: July 23, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Advanced Cancer; Metastatic Cancer; p70s6 inhibitor
• Other Study ID Numbers: 13871; I3G-JE-JGCC (Other Identifier: Eli Lilly and Company)