Trial Outcomes & Findings for C14 Study in Oncology Patients With Advanced and/or Metastatic Solid Tumors (NCT NCT01296568)
NCT ID: NCT01296568
Last Updated: 2019-01-07
Results Overview
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.
COMPLETED
PHASE1
3 participants
0 to 6 hours, 6 to 12, 12 to 24, 24 to 48, 48 to 72 and 72 to 96 hours post-dose
2019-01-07
Participant Flow
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.
Participant milestones
| Measure |
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.
|
|---|---|
|
[^14C]LY2603618 Single Dose and Washout
STARTED
|
3
|
|
[^14C]LY2603618 Single Dose and Washout
COMPLETED
|
3
|
|
[^14C]LY2603618 Single Dose and Washout
NOT COMPLETED
|
0
|
|
Continued Access Phase
STARTED
|
3
|
|
Continued Access Phase
COMPLETED
|
0
|
|
Continued Access Phase
NOT COMPLETED
|
3
|
Reasons for withdrawal
| Measure |
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.
|
|---|---|
|
Continued Access Phase
Lost to Follow-up
|
1
|
|
Continued Access Phase
Withdrawal by Subject
|
1
|
|
Continued Access Phase
Disease Progression
|
1
|
Baseline Characteristics
C14 Study in Oncology Patients With Advanced and/or Metastatic Solid Tumors
Baseline characteristics by cohort
| Measure |
Entire Study Population
n=3 Participants
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.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
2 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
3 Participants
n=5 Participants
|
|
Region of Enrollment
Switzerland
|
3 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 0 to 6 hours, 6 to 12, 12 to 24, 24 to 48, 48 to 72 and 72 to 96 hours post-dosePopulation: All enrolled participants.
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.
Outcome measures
| Measure |
[^14C]LY2603618
n=3 Participants
Participants in the first phase of the study 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.
|
|---|---|
|
Urinary and Fecal Excretion of LY2603618 Radioactivity Over Time Expressed as a Percentage of the Total Radioactive Dose Administered
Feces
|
72.2 percentage of total dose
Standard Deviation 2.52
|
|
Urinary and Fecal Excretion of LY2603618 Radioactivity Over Time Expressed as a Percentage of the Total Radioactive Dose Administered
Urine
|
11.0 percentage of total dose
Standard Deviation 0.57
|
SECONDARY outcome
Timeframe: 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dosePopulation: All enrolled participants.
Plasma LY2603618 Cmax following a single dose on Day 1.
Outcome measures
| Measure |
[^14C]LY2603618
n=3 Participants
Participants in the first phase of the study 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.
|
|---|---|
|
Plasma Pharmacokinetics of LY2603618: Maximum Observed Drug Concentration (Cmax)
|
4750 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 52
|
SECONDARY outcome
Timeframe: 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dosePopulation: All enrolled participants.
Plasma radioactivity Cmax \[nanogram equivalents per milliliter (ng Eq/mL)\] following a single dose on Day 1.
Outcome measures
| Measure |
[^14C]LY2603618
n=3 Participants
Participants in the first phase of the study 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.
|
|---|---|
|
Plasma Pharmacokinetics of Radioactivity: Maximum Observed Drug Concentration (Cmax)
|
5660 ng Eq/mL
Geometric Coefficient of Variation 47
|
SECONDARY outcome
Timeframe: 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dosePopulation: All enrolled participants.
Plasma LY2603618 AUC(0-infinity) following a single dose on Day 1.
Outcome measures
| Measure |
[^14C]LY2603618
n=3 Participants
Participants in the first phase of the study 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.
|
|---|---|
|
Plasma Pharmacokinetics of LY2603618: Area Under the Concentration Time Curve From Time Zero to Infinity [AUC(0-infinity)]
|
22300 nanograms*hours per milliliter (ng*h/mL)
Geometric Coefficient of Variation 48
|
SECONDARY outcome
Timeframe: 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dosePopulation: All enrolled participants.
Plasma radioactivity AUC(0-infinity) \[nanogram equivalents\*hours per milliliter (ng Eq\*h/mL)\] following a single dose on Day 1.
Outcome measures
| Measure |
[^14C]LY2603618
n=3 Participants
Participants in the first phase of the study 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.
|
|---|---|
|
Plasma Pharmacokinetics of Radioactivity: Area Under the Concentration Time Curve From Time Zero to Infinity [AUC(0-infinity)]
|
32500 ng Eq*h/mL
Geometric Coefficient of Variation 63
|
SECONDARY outcome
Timeframe: 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dosePopulation: All enrolled participants.
Plasma LY2603618 AUC(0-tlast) where tlast is the last time point with a measurable concentration following a single dose on Day 1.
Outcome measures
| Measure |
[^14C]LY2603618
n=3 Participants
Participants in the first phase of the study 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.
|
|---|---|
|
Plasma Pharmacokinetics of LY2603618: Area Under the Concentration Time Curve From Time Zero to Time t [AUC(0-tlast)]
|
22200 nanograms*hours per milliliter (ng*h/mL)
Geometric Coefficient of Variation 48
|
SECONDARY outcome
Timeframe: 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dosePopulation: All enrolled participants.
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.
Outcome measures
| Measure |
[^14C]LY2603618
n=3 Participants
Participants in the first phase of the study 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.
|
|---|---|
|
Plasma Pharmacokinetics of Radioactivity: Area Under the Concentration Time Curve From Time Zero to Time t [AUC(0-tlast)]
|
27700 ng Eq*h/mL
Geometric Coefficient of Variation 56
|
SECONDARY outcome
Timeframe: Day 1 through 7 days postdosePopulation: All enrolled participants.
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.
Outcome measures
| Measure |
[^14C]LY2603618
n=3 Participants
Participants in the first phase of the study 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.
|
|---|---|
|
Relative Abundance of LY2603618 and the Metabolites of LY2603618 in Urine
LY2603618 (parent)
|
3.3 percentage of [^14C]LY2603618
Interval 2.3 to 5.1
|
|
Relative Abundance of LY2603618 and the Metabolites of LY2603618 in Urine
Metabolites
|
3.0 percentage of [^14C]LY2603618
Interval 2.5 to 3.6
|
SECONDARY outcome
Timeframe: Day 1 through 7 days postdosePopulation: All enrolled participants.
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.
Outcome measures
| Measure |
[^14C]LY2603618
n=3 Participants
Participants in the first phase of the study 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.
|
|---|---|
|
Relative Abundance of LY2603618 and the Metabolites of LY2603618 in Feces
LY2603618 (parent)
|
5.6 percentage of [^14C]LY2603618
Interval 5.5 to 5.7
|
|
Relative Abundance of LY2603618 and the Metabolites of LY2603618 in Feces
Metabolites
|
61.4 percentage of [^14C]LY2603618
Interval 60.6 to 62.9
|
SECONDARY outcome
Timeframe: Baseline through study completion [Cycle 5 (28 days/cycle) and 21-day safety follow-up]Population: All enrolled participants who had radiological tumor assessment.
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.
Outcome measures
| Measure |
[^14C]LY2603618
n=2 Participants
Participants in the first phase of the study 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.
|
|---|---|
|
The Number of Participants With a Tumor Response
Complete response
|
0 Participants
|
|
The Number of Participants With a Tumor Response
Partial response
|
0 Participants
|
|
The Number of Participants With a Tumor Response
Progressive disease
|
2 Participants
|
|
The Number of Participants With a Tumor Response
Stable disease
|
0 Participants
|
Adverse Events
[^14C]LY2603618
LY2603618 + Gemcitabine
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
[^14C]LY2603618
n=3 participants at risk
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.
|
LY2603618 + Gemcitabine
n=3 participants at risk
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.
|
|---|---|---|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/3
|
33.3%
1/3 • Number of events 1
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/3
|
33.3%
1/3 • Number of events 1
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/3
|
33.3%
1/3 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/3
|
33.3%
1/3 • Number of events 1
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/3
|
33.3%
1/3 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/3
|
66.7%
2/3 • Number of events 3
|
|
Gastrointestinal disorders
Vomiting
|
33.3%
1/3 • Number of events 1
|
100.0%
3/3 • Number of events 5
|
|
General disorders
Chest discomfort
|
0.00%
0/3
|
33.3%
1/3 • Number of events 1
|
|
General disorders
Chills
|
33.3%
1/3 • Number of events 1
|
33.3%
1/3 • Number of events 1
|
|
General disorders
Fatigue
|
33.3%
1/3 • Number of events 1
|
0.00%
0/3
|
|
General disorders
Injection site reaction
|
33.3%
1/3 • Number of events 1
|
33.3%
1/3 • Number of events 1
|
|
General disorders
Malaise
|
0.00%
0/3
|
33.3%
1/3 • Number of events 1
|
|
General disorders
Oedema peripheral
|
0.00%
0/3
|
33.3%
1/3 • Number of events 2
|
|
General disorders
Pain
|
33.3%
1/3 • Number of events 1
|
33.3%
1/3 • Number of events 1
|
|
Infections and infestations
Herpes zoster
|
0.00%
0/3
|
33.3%
1/3 • Number of events 1
|
|
Infections and infestations
Rhinitis
|
0.00%
0/3
|
33.3%
1/3 • Number of events 1
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/3
|
66.7%
2/3 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
33.3%
1/3 • Number of events 1
|
0.00%
0/3
|
|
Nervous system disorders
Headache
|
33.3%
1/3 • Number of events 1
|
33.3%
1/3 • Number of events 1
|
|
Psychiatric disorders
Depression
|
0.00%
0/3
|
33.3%
1/3 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/3
|
66.7%
2/3 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Photosensitivity reaction
|
33.3%
1/3 • Number of events 1
|
0.00%
0/3
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/3
|
33.3%
1/3 • Number of events 1
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60