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

• ClinicalTrials.gov Identifier: NCT00415636
• Recruitment Status: Completed
• First Posted: December 25, 2006
• Results First Posted: October 19, 2018
• Last Update Posted: October 19, 2018
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: December 21, 2006
• First Posted Date: December 25, 2006
• Results First Submitted Date: February 17, 2018
• Results First Posted Date: October 19, 2018
• Last Update Posted Date: October 19, 2018
• Study Start Date: January 2007
• Actual Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 26, 2018)

Number of Participants With Adverse Events (AEs) [ Time Frame: baseline up to 24 months ]

Summary tables of serious AEs (SAEs) and all other non-serious adverse events (AEs) are located in the Reported Adverse Event Module.

• Original Primary Outcome Measures (submitted: December 21, 2006): Safety and Tolerability of IC83

Current Secondary Outcome Measures (submitted: March 26, 2018)

• Pharmacokinetic (PK) Parameter: Maximum Observed Plasma Concentration (Cmax) of IC83/LY2603618 [ Time Frame: Day 1 and Day 9 of Cycle 1 ]
  Cmax was estimated from the plasma concentration data of LY2603618 versus time profiles.
• Pharmacokinetic (PK) Parameter: Area Under the IC83/LY2603618 Plasma Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-∞]) [ Time Frame: Day 1 and Day 9 of Cycle 1 ]
  AUC[0-∞] was calculated from the plasma concentration data of LY2603618 versus time profiles.
• Percentage of Participants With Best Overall Response [ Time Frame: baseline up to 24 months ]
  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.

• Original Secondary Outcome Measures (submitted: December 21, 2006): Pharmacokinetic Parameters will be determined. Efficacy endpoints will include tumor response, time to radiologic or clinical tumor progression, and progression free survival
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Tolerability of IC83/LY2603618 Administered After Pemetrexed 500 mg/m2 Every 21 Days in Patients With Cancer
• Official Title: 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
• Brief Summary: The purpose of this study is to evaluate the safety and tolerability of IC83/LY2603618 for the treatment of cancer.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Cancer

Intervention

• 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

Study Arms

• 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.
  Interventions:

  • Drug: IC83/LY2603618
  • Drug: pemetrexed
• 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.
  Interventions:

  • Drug: IC83/LY2603618
  • Drug: pemetrexed
• 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.
  Interventions:

  • Drug: IC83/LY2603618
  • Drug: pemetrexed
• Experimental: LY2603618 105 mg/m^2
  Cohort 4: LY2603618 105 mg/m^2 administered over the duration of 1 hour.
  Interventions:

  • Drug: IC83/LY2603618
  • Drug: pemetrexed
• Experimental: LY2603618 150 mg/m^2
  Cohort 5: LY2603618 150 mg/m^2 administered over the duration of 1 hour.
  Interventions:

  • Drug: IC83/LY2603618
  • Drug: pemetrexed
• Experimental: LY2603618 195 mg/m^2
  Cohort 6: LY2603618 195 mg/m^2 administered over the duration of 1 hour.
  Interventions:

  • Drug: IC83/LY2603618
  • Drug: pemetrexed

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 17, 2010): 31
• Original Enrollment (submitted: December 21, 2006): 80
• Actual Study Completion Date: July 2010
• Actual Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00415636
• Other Study ID Numbers: 11911; I2I-MC-JMMB ( Other Identifier: Eli Lilly and Company )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Eli Lilly and Company
• Study Sponsor: Eli Lilly and Company
• Collaborators: Not Provided

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

• PRS Account: Eli Lilly and Company
• Verification Date: March 2018