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| ID | Type | Description | Link |
|---|---|---|---|
| I2I-MC-JMMH | Other Identifier | Eli Lilly and Company |
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This is an open-label study being conducted to determine the metabolism and physiological disposition of radiolabeled LY2603618 after a single dose in patients with advanced and/or metastatic solid tumors.
After a minimum 7-day washout period following the carbon-14-labeled LY2603618 ([^14C]LY2603618) dose, patients will be allowed to continue to receive continued access to LY2603618 in combination with pemetrexed or gemcitabine as outpatients.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LY2603618 | Experimental | Single 250 milligram (mg) intravenous dose of LY2603618 containing carbon-14-labeled LY2603618 ([^14C]LY2603618). After the completion of a minimum 7-day washout period, participants may receive additional doses of LY2603618 in combination as follows:
Participants will be allowed to continue to receive the combination therapy until fulfilling one of the criteria for discontinuation, such as unacceptable toxicity or disease progression. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LY2603618 | Drug | Administered intravenously |
| |
| Pemetrexed |
| Measure | Description | Time Frame |
|---|---|---|
| Urinary and Fecal Excretion of LY2603618 Radioactivity Over Time Expressed as a Percentage of the Total Radioactive Dose Administered | Urinary and fecal excretion samples from each participant were measured by liquid scintillation counting. The radioactive counts detected in urine and fecal samples were each divided by the theoretical radioactive count in the total radioactive dose administered and multiplied by 100% to arrive at a percentage of total radioactive dose excreted in urine and feces. | 0 to 6 hours, 6 to 12, 12 to 24, 24 to 48, 48 to 72 and 72 to 96 hours post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma Pharmacokinetics of LY2603618: Maximum Observed Drug Concentration (Cmax) | Plasma LY2603618 Cmax following a single dose on Day 1. | 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dose |
| Plasma Pharmacokinetics of Radioactivity: Maximum Observed Drug Concentration (Cmax) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| 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 Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 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. | Bruderholz | 4101 |
Study had 2 phases. First phase: participants (pts) received single dose of carbon-14-labeled LY2603618 ([^14C]LY2603618) and completed a minimum 7-day washout. Second phase: pts had option to continue receiving LY2603618 in combination with gemcitabine or pemetrexed. All pts chose to receive gemcitabine for combination treatment.
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| ID | Title | Description |
|---|---|---|
| FG000 | Entire Study Population | In the [^14C]LY2603618 Single Dose and Washout Phase (first phase), participants received a single 250 milligram (mg) dose of LY2603618 containing [^14C]LY2603618, administered as a 1-hour intravenous infusion. Participants then completed a minimum 7-day washout period. In the Continued Access Phase (second phase), participants received additional doses of LY2603618 in combination with gemcitabine as follows: • Gemcitabine 1000 milligrams per square meter (mg/m^2) administered as an intravenous infusion on Days 1, 8, and 15 with 230 mg LY2603618 administered intravenously on Days 2, 9 and 16 of a 28-day cycle. Participants were allowed to continue to receive the combination therapy until fulfilling 1 of the criteria for discontinuation, such as unacceptable toxicity or disease progression. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| [^14C]LY2603618 Single Dose and Washout |
| |||||||||||||
| Continued Access Phase |
|
All enrolled participants.
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| ID | Title | Description |
|---|---|---|
| BG000 | Entire Study Population | In the [^14C]LY2603618 Single Dose and Washout Phase (first phase), participants received a single 250 milligram (mg) dose of LY2603618 containing [^14C]LY2603618, administered as a 1-hour intravenous infusion. Participants then completed a minimum 7-day washout period. In the Continued Access Phase (second phase), participants received additional doses of LY2603618 in combination with gemcitabine as follows: • Gemcitabine 1000 milligrams per square meter (mg/m^2) administered as an intravenous infusion on Days 1, 8, and 15 with 230 mg LY2603618 administered intravenously on Days 2, 9 and 16 of a 28-day cycle. Participants were allowed to continue to receive the combination therapy until fulfilling 1 of the criteria for discontinuation, such as unacceptable toxicity or disease progression. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Urinary and Fecal Excretion of LY2603618 Radioactivity Over Time Expressed as a Percentage of the Total Radioactive Dose Administered | Urinary and fecal excretion samples from each participant were measured by liquid scintillation counting. The radioactive counts detected in urine and fecal samples were each divided by the theoretical radioactive count in the total radioactive dose administered and multiplied by 100% to arrive at a percentage of total radioactive dose excreted in urine and feces. | All enrolled participants. | Posted | Mean | Standard Deviation | percentage of total dose | 0 to 6 hours, 6 to 12, 12 to 24, 24 to 48, 48 to 72 and 72 to 96 hours post-dose |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | [^14C]LY2603618 | Adverse events reported during the first phase of the study. Participants received a single 250 milligram (mg) intravenous dose of LY2603618 containing [^14C]LY2603618 and then completed a minimum 7-day washout period. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Leukopenia | Blood and lymphatic system disorders | MedDRA 13.0 | Systematic Assessment |
Study stopped early due to low enrollment, therefore data for evaluation was limited. Study not designed for efficacy assessments, however, tumor response data was collected and reported during Continued Access Phase.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Eli Lilly and Company | 800-545-5979 |
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| ID | Term |
|---|---|
| C582547 | LY2603618 |
| D000068437 | Pemetrexed |
| D000093542 | Gemcitabine |
| ID | Term |
|---|---|
| D006147 | Guanine |
| D007042 | Hypoxanthines |
| D011688 | Purinones |
| D011687 | Purines |
| D006574 |
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| Drug |
Administered intravenously |
|
|
| Gemcitabine | Drug | Administered intravenously |
|
|
Plasma radioactivity Cmax [nanogram equivalents per milliliter (ng Eq/mL)] following a single dose on Day 1. |
| 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dose |
| Plasma Pharmacokinetics of LY2603618: Area Under the Concentration Time Curve From Time Zero to Infinity [AUC(0-infinity)] | Plasma LY2603618 AUC(0-infinity) following a single dose on Day 1. | 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dose |
| Plasma Pharmacokinetics of Radioactivity: Area Under the Concentration Time Curve From Time Zero to Infinity [AUC(0-infinity)] | Plasma radioactivity AUC(0-infinity) [nanogram equivalents*hours per milliliter (ng Eq*h/mL)] following a single dose on Day 1. | 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dose |
| Plasma Pharmacokinetics of LY2603618: Area Under the Concentration Time Curve From Time Zero to Time t [AUC(0-tlast)] | Plasma LY2603618 AUC(0-tlast) where tlast is the last time point with a measurable concentration following a single dose on Day 1. | 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dose |
| Plasma Pharmacokinetics of Radioactivity: Area Under the Concentration Time Curve From Time Zero to Time t [AUC(0-tlast)] | Plasma radioactivity AUC(0-tlast) [nanogram equivalents*hours per milliliter (ng Eq*h/mL)] where tlast is the last time point with a measurable concentration following a single dose on Day 1. | 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dose |
| Relative Abundance of LY2603618 and the Metabolites of LY2603618 in Urine | Relative abundance was expressed as the percentage of the dose of study drug administered and calculated as %=[amount of LY2603618 or its metabolites excreted/amount of radioactive dose administered]*100. | Day 1 through 7 days postdose |
| Relative Abundance of LY2603618 and the Metabolites of LY2603618 in Feces | Relative abundance was expressed as the percentage of the dose of study drug administered and calculated as %=[amount of LY2603618 or its metabolites excreted/amount of radioactive dose administered]*100. | Day 1 through 7 days postdose |
| The Number of Participants With a Tumor Response | Tumor responses were followed and measured according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete response was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter (mm) and normalization of tumor marker level of non-target lesions. Partial response was defined as at least a 30% decrease in sum of longest diameter of target lesions. Progressive disease was defined as at least 20% increase in sum of longest diameter of target lesions and minimum 5 mm increase over nadir; Stable disease was defined as small changes that did not meet above criteria. | Baseline through study completion [Cycle 5 (28 days/cycle) and 21-day safety follow-up] |
| Switzerland |
|
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
|
|
| Secondary | Plasma Pharmacokinetics of LY2603618: Maximum Observed Drug Concentration (Cmax) | Plasma LY2603618 Cmax following a single dose on Day 1. | All enrolled participants. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms per milliliter (ng/mL) | 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dose |
|
|
|
| Secondary | Plasma Pharmacokinetics of Radioactivity: Maximum Observed Drug Concentration (Cmax) | Plasma radioactivity Cmax [nanogram equivalents per milliliter (ng Eq/mL)] following a single dose on Day 1. | All enrolled participants. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng Eq/mL | 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dose |
|
|
|
| Secondary | Plasma Pharmacokinetics of LY2603618: Area Under the Concentration Time Curve From Time Zero to Infinity [AUC(0-infinity)] | Plasma LY2603618 AUC(0-infinity) following a single dose on Day 1. | All enrolled participants. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms*hours per milliliter (ng*h/mL) | 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dose |
|
|
|
| Secondary | Plasma Pharmacokinetics of Radioactivity: Area Under the Concentration Time Curve From Time Zero to Infinity [AUC(0-infinity)] | Plasma radioactivity AUC(0-infinity) [nanogram equivalents*hours per milliliter (ng Eq*h/mL)] following a single dose on Day 1. | All enrolled participants. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng Eq*h/mL | 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dose |
|
|
|
| Secondary | Plasma Pharmacokinetics of LY2603618: Area Under the Concentration Time Curve From Time Zero to Time t [AUC(0-tlast)] | Plasma LY2603618 AUC(0-tlast) where tlast is the last time point with a measurable concentration following a single dose on Day 1. | All enrolled participants. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms*hours per milliliter (ng*h/mL) | 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dose |
|
|
|
| Secondary | Plasma Pharmacokinetics of Radioactivity: Area Under the Concentration Time Curve From Time Zero to Time t [AUC(0-tlast)] | Plasma radioactivity AUC(0-tlast) [nanogram equivalents*hours per milliliter (ng Eq*h/mL)] where tlast is the last time point with a measurable concentration following a single dose on Day 1. | All enrolled participants. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng Eq*h/mL | 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dose |
|
|
|
| Secondary | Relative Abundance of LY2603618 and the Metabolites of LY2603618 in Urine | Relative abundance was expressed as the percentage of the dose of study drug administered and calculated as %=[amount of LY2603618 or its metabolites excreted/amount of radioactive dose administered]*100. | All enrolled participants. | Posted | Mean | Full Range | percentage of [^14C]LY2603618 | Day 1 through 7 days postdose |
|
|
|
| Secondary | Relative Abundance of LY2603618 and the Metabolites of LY2603618 in Feces | Relative abundance was expressed as the percentage of the dose of study drug administered and calculated as %=[amount of LY2603618 or its metabolites excreted/amount of radioactive dose administered]*100. | All enrolled participants. | Posted | Mean | Full Range | percentage of [^14C]LY2603618 | Day 1 through 7 days postdose |
|
|
|
| Secondary | The Number of Participants With a Tumor Response | Tumor responses were followed and measured according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete response was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter (mm) and normalization of tumor marker level of non-target lesions. Partial response was defined as at least a 30% decrease in sum of longest diameter of target lesions. Progressive disease was defined as at least 20% increase in sum of longest diameter of target lesions and minimum 5 mm increase over nadir; Stable disease was defined as small changes that did not meet above criteria. | All enrolled participants who had radiological tumor assessment. | Posted | Count of Participants | Participants | No | Baseline through study completion [Cycle 5 (28 days/cycle) and 21-day safety follow-up] |
|
|
|
| 0 |
| 3 |
| 3 |
| 3 |
| EG001 | LY2603618 + Gemcitabine | Adverse events reported during the second phase of the study. After completing the first phase [a single 250 milligram (mg) intravenous dose of LY2603618 containing [^14C]LY2603618 followed by a minimum 7-day washout period], participants received Gemcitabine 1000 milligrams per square meter (mg/m^2) administered intravenously on Days 1, 8, and 15 with 230 mg LY2603618 administered intravenously on Days 2, 9 and 16 of a 28-day cycle until unacceptable toxicity or disease progression. | 0 | 3 | 3 | 3 |
| Neutropenia | Blood and lymphatic system disorders | MedDRA 13.0 | Systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 13.0 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA 13.0 | Systematic Assessment |
|
| Chills | General disorders | MedDRA 13.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 13.0 | Systematic Assessment |
|
| Injection site reaction | General disorders | MedDRA 13.0 | Systematic Assessment |
|
| Malaise | General disorders | MedDRA 13.0 | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA 13.0 | Systematic Assessment |
|
| Pain | General disorders | MedDRA 13.0 | Systematic Assessment |
|
| Herpes zoster | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA 13.0 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 13.0 | Systematic Assessment |
|
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 13.0 | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA 13.0 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 13.0 | Systematic Assessment |
|
| Photosensitivity reaction | Skin and subcutaneous tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 13.0 | Systematic Assessment |
|
Not provided
| Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D005971 | Glutamates |
| D024342 | Amino Acids, Acidic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D000600 | Amino Acids, Dicarboxylic |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| Title | Measurements |
|---|---|
|
| Stable disease |
|