C14 Study In Oncology Patients With Advanced And/or Metastatic Solid Tumors

Study Overview

C14 Study in Oncology Patients With Advanced and/or Metastatic Solid Tumors

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.

N/A

Advanced Cancer

DRUG: LY2603618
DRUG: Pemetrexed
DRUG: Gemcitabine

13525
I2I-MC-JMMH (OTHER Identifier) (OTHER: Eli Lilly and Company)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2011-02-14	Results First Submitted 2018-02-17	Last Update Submitted that met QC Criteria 2018-12-12
First Submitted that Met QC Criteria 2011-02-14	Results First Submitted that Met QC Criteria 2018-03-26	Last Update Posted (ACTUAL) 2019-01-07
First Posted (ACTUAL) 2011-02-15	Results First Posted 2018-10-25	Last Verified 2018-12

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: LY2603618 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: *	DRUG: LY2603618 Administered intravenously DRUG: Pemetrexed Administered intravenously DRUG: Gemcitabine Administered intravenously

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: LY2603618

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: *

DRUG: LY2603618

Administered intravenously

DRUG: Pemetrexed

Administered intravenously

DRUG: Gemcitabine

Administered intravenously

Primary Outcome Measures	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

Secondary Outcome Measures	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)	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 equivalentshours per milliliter (ng Eqh/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 equivalentshours per milliliter (ng Eqh/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]

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Have a histological or cytological diagnosis of cancer (solid tumor), with clinical or radiologic evidence of locally advanced and/or metastatic disease, for which no life-prolonging therapy exists (that is, refractory to standard therapy and/or therapies known to provide clinical benefit, or for which no standard therapy exists). Note: participants who have had progressive disease after receiving pemetrexed for metastatic disease are excluded from receiving the combination with pemetrexed during the safety extension study. Participants who have had progressive disease after receiving gemcitabine for metastatic disease are excluded from receiving the combination with gemcitabine during the safety extension study.
Have a body surface area greater than or equal to 1.37 meters squared (m^2)
Have given written informed consent prior to any study-specific procedures
Adequate hematologic, hepatic and renal function
Have a performance status of less than or equal to 2 on the Eastern Cooperative Oncology Group (ECOG) scale
Have discontinued all previous treatments for cancer, including chemotherapy, radiotherapy, anticancer hormone therapy, or other investigational therapy for at least 30 days prior to study entry and recovered from the acute effects of therapy (at least 42 days for mitomycin-C or nitrosoureas, or 60 days for monoclonal antibodies)
Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedure
Males and females with reproductive potential: Must agree to use medically approved contraceptive precautions during the study and following the last dose of study drug until, in the judgment of the investigator, it is safe for the participant to become pregnant or father a child
Females with childbearing potential: Have had a negative serum pregnancy test less than or equal to 7 days before the first dose of study drug and must also not be breastfeeding
Have an estimated life expectancy that, in the judgment of the investigator, will permit the participant to complete 1 full cycle of treatment (beyond the initial [^14C]LY2603618 dose)
Prior radiation therapy for treatment of cancer other than pancreatic is allowed to <25% of the bone marrow and participants must have recovered from the acute toxic effects of their treatment prior to study enrollment. Prior radiation to the whole pelvis is not allowed. Prior radiotherapy must be completed at least 4 weeks before study entry.

Have received treatment within 28 days of the initial dose of study drug with an experimental agent for noncancer indications that has not received regulatory approval for any indication
Have previously completed or withdrawn from this study or any other study investigating LY2603618 or any other checkpoint kinase one (Chk1) inhibitor
Have a known allergy to gemcitabine, pemetrexed, LY2603618, or any ingredient of gemcitabine, pemetrexed, or LY2603618 (like Captisol)
Have serious preexisting medical conditions (left to the discretion of the investigator) other than advanced cancer
Have symptomatic central nervous system (CNS) malignancy or metastasis (screening not required). Participants with treated CNS metastases are eligible for this study if they are not currently receiving corticosteroids and/or anticonvulsants, and their disease is asymptomatic and radiographically stable for at least 90 days
Have current hematologic malignancies or either acute or chronic leukemia
Have an active fungal, bacterial, and/or known viral infection including human immunodeficiency virus (HIV) or viral (A, B, or C) hepatitis (screening is not required)
Have a QTc interval of >500 milliseconds (msec) on the screening electrocardiogram (ECG)
Have ECG abnormalities on the screening ECG such as significant conduction abnormalities, ischemic changes (such as prior Q-wave myocardial infarction and/or marked ischemic ST- and T-wave), arrhythmias (such as persistent or paroxysmal ventricular or supraventricular arrhythmias, including atrial fibrillation), or other ECG abnormalities that would put the participant at unnecessary risk in the opinion of the investigator
Have participated in a ^14C study within the last 6 months prior to screening for this study. The total exposure from this study and the previous study must be less than 5 milliSieverts (mSv).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

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

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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