Safety and Tolerability of IC83/LY2603618 Administered After Pemetrexed 500 mg/m2 Every 21 Days in Patients With Cancer

A Phase 1 Dose-Escalation Study to Examine the Safety and Tolerability of IC83/LY2603618 Administered After Pemetrexed 500 mg/m2 Every 21 Days in Patients With Cancer

The purpose of this study is to evaluate the safety and tolerability of IC83/LY2603618 for the treatment of cancer.

Study Overview

• Status: Completed
• Conditions: Cancer
• Intervention / Treatment: Drug: IC83/LY2603618; Drug: IC83/LY2603618; Drug: IC83/LY2603618; Drug: IC83/LY2603618; Drug: IC83/LY2603618; Drug: pemetrexed; Drug: pemetrexed

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • 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:

• Has at least one lesion that can be evaluated by Response Evaluation Criteria In Solid Tumors (RECIST)

• Has fully recovered from all toxicities due to the following:

  1. Local radiation therapy that ended at least 14 days prior to Cycle 1, Day 1.
  2. Surgery.
• Has a life expectancy of at least 3 months.
• Negative serum pregnancy test.

Exclusion Criteria:

• Is pregnant or breastfeeding.
• Is a woman of childbearing potential unwilling to use an approved, effective means of contraception according to the institution's standards.
• Is a man of childbearing potential unwilling to use an approved, effective means of contraception according to the institution's standards.
• Has a history of brain metastases, unless adequately treated and without radiologic evidence of progressive disease for at least 3 months after completion of therapy.
• Has a known active infection.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LY2603618 40 mg/m^2 (4.5-hour infusion); LY2603618 40 milligrams per square meter (mg/m^2) was administered over the duration of 4.5 hours (30-minute bolus followed by a 4-hour infusion). Dose modifications were not allowed.	Drug: IC83/LY2603618; 40 mg/m^2 Day 1 and Day 9 of Cycle 1, Day 2 of subsequent cycles, unlimited 21-day cycles. Dose finding study: dose is escalated after a minimum of 6 participants receive 40 mg/m^2.; Drug: IC83/LY2603618; 70 mg/m^2 Day 1 and Day 9 of Cycle 1, Day 2 of subsequent cycles, unlimited 21-day cycles.; Drug: IC83/LY2603618; 105 mg/m^2 Day 1 and Day 9 of Cycle 1, Day 2 of subsequent cycles, unlimited 21-day cycles.; Drug: IC83/LY2603618; 150 mg/m^2 Day 1 and Day 9 of Cycle 1, Day 2 of subsequent cycles, unlimited 21-day cycles.; Drug: IC83/LY2603618; 195 mg/m^2 Day 1 and Day 9 of Cycle 1, Day 2 of subsequent cycles, unlimited 21-day cycles.; Drug: pemetrexed; pemetrexed 500 mg/m^2, intravenous (IV), Day 8 of Cycle 1, Day 1 of subsequent cycles, unlimited 21-day cycles; Other Names: Alimta; LY231514; Drug: pemetrexed; pemetrexed 500 mg/m^2 IV, Day 8 of Cycle 1, Day 1 of subsequent cycles, unlimited 21-day cycles
Experimental: LY2603618 40 mg/m^2 (1-hour infusion); Based on pharmacokinetic (PK) data from Cohort 1 (LY2603618 40 mg/m^2 [4.5-hour infusion]), the LY2603618 40 mg/m^2 dose in Cohort 2 (LY2603618 40 mg/m^2 [1-hour infusion]) was repeated, but the dose was administered over the duration of 1 hour. Dose modifications were not allowed.	Drug: IC83/LY2603618; 40 mg/m^2 Day 1 and Day 9 of Cycle 1, Day 2 of subsequent cycles, unlimited 21-day cycles. Dose finding study: dose is escalated after a minimum of 6 participants receive 40 mg/m^2.; Drug: IC83/LY2603618; 70 mg/m^2 Day 1 and Day 9 of Cycle 1, Day 2 of subsequent cycles, unlimited 21-day cycles.; Drug: IC83/LY2603618; 105 mg/m^2 Day 1 and Day 9 of Cycle 1, Day 2 of subsequent cycles, unlimited 21-day cycles.; Drug: IC83/LY2603618; 150 mg/m^2 Day 1 and Day 9 of Cycle 1, Day 2 of subsequent cycles, unlimited 21-day cycles.; Drug: IC83/LY2603618; 195 mg/m^2 Day 1 and Day 9 of Cycle 1, Day 2 of subsequent cycles, unlimited 21-day cycles.; Drug: pemetrexed; pemetrexed 500 mg/m^2, intravenous (IV), Day 8 of Cycle 1, Day 1 of subsequent cycles, unlimited 21-day cycles; Other Names: Alimta; LY231514; Drug: pemetrexed; pemetrexed 500 mg/m^2 IV, Day 8 of Cycle 1, Day 1 of subsequent cycles, unlimited 21-day cycles
Experimental: LY2603618 70 mg/m^2; Beginning with Cohort 3 (LY2603618 70 mg/m^2), dose modifications were allowed. LY2603618 70 mg/m^2 was administered over the course of 1 hour.	Drug: IC83/LY2603618; 40 mg/m^2 Day 1 and Day 9 of Cycle 1, Day 2 of subsequent cycles, unlimited 21-day cycles. Dose finding study: dose is escalated after a minimum of 6 participants receive 40 mg/m^2.; Drug: IC83/LY2603618; 70 mg/m^2 Day 1 and Day 9 of Cycle 1, Day 2 of subsequent cycles, unlimited 21-day cycles.; Drug: IC83/LY2603618; 105 mg/m^2 Day 1 and Day 9 of Cycle 1, Day 2 of subsequent cycles, unlimited 21-day cycles.; Drug: IC83/LY2603618; 150 mg/m^2 Day 1 and Day 9 of Cycle 1, Day 2 of subsequent cycles, unlimited 21-day cycles.; Drug: IC83/LY2603618; 195 mg/m^2 Day 1 and Day 9 of Cycle 1, Day 2 of subsequent cycles, unlimited 21-day cycles.; Drug: pemetrexed; pemetrexed 500 mg/m^2, intravenous (IV), Day 8 of Cycle 1, Day 1 of subsequent cycles, unlimited 21-day cycles; Other Names: Alimta; LY231514; Drug: pemetrexed; pemetrexed 500 mg/m^2 IV, Day 8 of Cycle 1, Day 1 of subsequent cycles, unlimited 21-day cycles
Experimental: LY2603618 105 mg/m^2; Cohort 4: LY2603618 105 mg/m^2 administered over the duration of 1 hour.	Drug: IC83/LY2603618; 40 mg/m^2 Day 1 and Day 9 of Cycle 1, Day 2 of subsequent cycles, unlimited 21-day cycles. Dose finding study: dose is escalated after a minimum of 6 participants receive 40 mg/m^2.; Drug: IC83/LY2603618; 70 mg/m^2 Day 1 and Day 9 of Cycle 1, Day 2 of subsequent cycles, unlimited 21-day cycles.; Drug: IC83/LY2603618; 105 mg/m^2 Day 1 and Day 9 of Cycle 1, Day 2 of subsequent cycles, unlimited 21-day cycles.; Drug: IC83/LY2603618; 150 mg/m^2 Day 1 and Day 9 of Cycle 1, Day 2 of subsequent cycles, unlimited 21-day cycles.; Drug: IC83/LY2603618; 195 mg/m^2 Day 1 and Day 9 of Cycle 1, Day 2 of subsequent cycles, unlimited 21-day cycles.; Drug: pemetrexed; pemetrexed 500 mg/m^2, intravenous (IV), Day 8 of Cycle 1, Day 1 of subsequent cycles, unlimited 21-day cycles; Other Names: Alimta; LY231514; Drug: pemetrexed; pemetrexed 500 mg/m^2 IV, Day 8 of Cycle 1, Day 1 of subsequent cycles, unlimited 21-day cycles
Experimental: LY2603618 150 mg/m^2; Cohort 5: LY2603618 150 mg/m^2 administered over the duration of 1 hour.	Drug: IC83/LY2603618; 40 mg/m^2 Day 1 and Day 9 of Cycle 1, Day 2 of subsequent cycles, unlimited 21-day cycles. Dose finding study: dose is escalated after a minimum of 6 participants receive 40 mg/m^2.; Drug: IC83/LY2603618; 70 mg/m^2 Day 1 and Day 9 of Cycle 1, Day 2 of subsequent cycles, unlimited 21-day cycles.; Drug: IC83/LY2603618; 105 mg/m^2 Day 1 and Day 9 of Cycle 1, Day 2 of subsequent cycles, unlimited 21-day cycles.; Drug: IC83/LY2603618; 150 mg/m^2 Day 1 and Day 9 of Cycle 1, Day 2 of subsequent cycles, unlimited 21-day cycles.; Drug: IC83/LY2603618; 195 mg/m^2 Day 1 and Day 9 of Cycle 1, Day 2 of subsequent cycles, unlimited 21-day cycles.; Drug: pemetrexed; pemetrexed 500 mg/m^2, intravenous (IV), Day 8 of Cycle 1, Day 1 of subsequent cycles, unlimited 21-day cycles; Other Names: Alimta; LY231514; Drug: pemetrexed; pemetrexed 500 mg/m^2 IV, Day 8 of Cycle 1, Day 1 of subsequent cycles, unlimited 21-day cycles
Experimental: LY2603618 195 mg/m^2; Cohort 6: LY2603618 195 mg/m^2 administered over the duration of 1 hour.	Drug: IC83/LY2603618; 40 mg/m^2 Day 1 and Day 9 of Cycle 1, Day 2 of subsequent cycles, unlimited 21-day cycles. Dose finding study: dose is escalated after a minimum of 6 participants receive 40 mg/m^2.; Drug: IC83/LY2603618; 70 mg/m^2 Day 1 and Day 9 of Cycle 1, Day 2 of subsequent cycles, unlimited 21-day cycles.; Drug: IC83/LY2603618; 105 mg/m^2 Day 1 and Day 9 of Cycle 1, Day 2 of subsequent cycles, unlimited 21-day cycles.; Drug: IC83/LY2603618; 150 mg/m^2 Day 1 and Day 9 of Cycle 1, Day 2 of subsequent cycles, unlimited 21-day cycles.; Drug: IC83/LY2603618; 195 mg/m^2 Day 1 and Day 9 of Cycle 1, Day 2 of subsequent cycles, unlimited 21-day cycles.; Drug: pemetrexed; pemetrexed 500 mg/m^2, intravenous (IV), Day 8 of Cycle 1, Day 1 of subsequent cycles, unlimited 21-day cycles; Other Names: Alimta; LY231514; Drug: pemetrexed; pemetrexed 500 mg/m^2 IV, Day 8 of Cycle 1, Day 1 of subsequent cycles, unlimited 21-day cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs)	Summary tables of serious AEs (SAEs) and all other non-serious adverse events (AEs) are located in the Reported Adverse Event Module.	baseline up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic (PK) Parameter: Maximum Observed Plasma Concentration (Cmax) of IC83/LY2603618	Cmax was estimated from the plasma concentration data of LY2603618 versus time profiles.	Day 1 and Day 9 of Cycle 1
Pharmacokinetic (PK) Parameter: Area Under the IC83/LY2603618 Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞])	AUC[0-∞] was calculated from the plasma concentration data of LY2603618 versus time profiles.	Day 1 and Day 9 of Cycle 1
Percentage of Participants With Best Overall Response	Percentage of participants with tumor response (best confirmed overall response) assessed as complete response (CR) or partial response (PR) to treatment according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria. CR=disappearance of all target lesions; PR=30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD)=20% increase in sum of longest diameter of target lesions; Stable Disease (SD) =small changes that do not meet above criteria. Best Overall Response (%)=number of participants with CR+PR/number of participants in treatment arm * 100.	baseline up to 24 months

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9AM-5PM Eastern time (UTC/GMT-5 hours, EST), Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: December 21, 2006
• First Submitted That Met QC Criteria: December 21, 2006
• First Posted (Estimate): December 25, 2006

Study Record Updates

• Last Update Posted (Actual): October 19, 2018
• Last Update Submitted That Met QC Criteria: March 26, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Folic Acid Antagonists; Pemetrexed
• Other Study ID Numbers: 11911; I2I-MC-JMMB (Other Identifier: Eli Lilly and Company)