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

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

Official Title
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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

Conditions
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Cancer

Intervention / Treatment
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* Drug: IC83/LY2603618
* Drug: IC83/LY2603618
* Drug: IC83/LY2603618
* Drug: IC83/LY2603618
* Drug: IC83/LY2603618
* Drug: pemetrexed
* Drug: pemetrexed


Participation Criteria
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Eligibility Criteria
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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: Local radiation therapy that ended at least 14 days prior to Cycle 1, Day 1. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY2603618 40 mg/m^2 (4.5-hour infusion)<br>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<br>* 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.<br>Drug: pemetrexed<br>* pemetrexed 500 mg/m^2, intravenous (IV), Day 8 of Cycle 1, Day 1 of subsequent cycles, unlimited 21-day cycles<br>* Other names: LY231514;|
| Experimental: LY2603618 40 mg/m^2 (1-hour infusion)<br>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<br>* 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.<br>Drug: pemetrexed<br>* pemetrexed 500 mg/m^2 IV, Day 8 of Cycle 1, Day 1 of subsequent cycles, unlimited 21-day cycles<br>|
| Experimental: LY2603618 70 mg/m^2<br>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<br>* 70 mg/m^2 Day 1 and Day 9 of Cycle 1, Day 2 of subsequent cycles, unlimited 21-day cycles.<br>Drug: pemetrexed<br>* pemetrexed 500 mg/m^2 IV, Day 8 of Cycle 1, Day 1 of subsequent cycles, unlimited 21-day cycles<br>|
| Experimental: LY2603618 105 mg/m^2<br>Cohort 4: LY2603618 105 mg/m^2 administered over the duration of 1 hour. | Drug: IC83/LY2603618<br>* 105 mg/m^2 Day 1 and Day 9 of Cycle 1, Day 2 of subsequent cycles, unlimited 21-day cycles.<br>Drug: pemetrexed<br>* pemetrexed 500 mg/m^2 IV, Day 8 of Cycle 1, Day 1 of subsequent cycles, unlimited 21-day cycles<br>|
| Experimental: LY2603618 150 mg/m^2<br>Cohort 5: LY2603618 150 mg/m^2 administered over the duration of 1 hour. | Drug: IC83/LY2603618<br>* 150 mg/m^2 Day 1 and Day 9 of Cycle 1, Day 2 of subsequent cycles, unlimited 21-day cycles.<br>Drug: pemetrexed<br>* pemetrexed 500 mg/m^2 IV, Day 8 of Cycle 1, Day 1 of subsequent cycles, unlimited 21-day cycles<br>|
| Experimental: LY2603618 195 mg/m^2<br>Cohort 6: LY2603618 195 mg/m^2 administered over the duration of 1 hour. | Drug: IC83/LY2603618<br>* 195 mg/m^2 Day 1 and Day 9 of Cycle 1, Day 2 of subsequent cycles, unlimited 21-day cycles.<br>Drug: pemetrexed<br>* pemetrexed 500 mg/m^2 IV, Day 8 of Cycle 1, Day 1 of subsequent cycles, unlimited 21-day cycles<br>|

What is the study measuring?
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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 |