Clinical trial NCT01296568: C14 Study in Oncology Patients With Advanced and/or Metastatic Solid Tumors
Official title: Disposition of [14C]LY2603618 Following Intravenous Administration in Patients With Advanced and/or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Cancer
Keywords: metastatic solid tumors
Malignant/M-Neoplasm
Pancreas NOS
Absorption
Distribution
Metabolism
Excretion
Mass balance
Metabolic profile
Radiolabeled study
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2011-02-15
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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).

Primary outcomes:
measure: Urinary and Fecal Excretion of LY2603618 Radioactivity Over Time Expressed as a Percentage of the Total Radioactive Dose Administered
timeFrame: 0 to 6 hours, 6 to 12, 12 to 24, 24 to 48, 48 to 72 and 72 to 96 hours post-dose
Secondary outcomes:
measure: Plasma Pharmacokinetics of LY2603618: Maximum Observed Drug Concentration (Cmax)
timeFrame: 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
measure: Plasma Pharmacokinetics of Radioactivity: Maximum Observed Drug Concentration (Cmax)
timeFrame: 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
measure: Plasma Pharmacokinetics of LY2603618: Area Under the Concentration Time Curve From Time Zero to Infinity [AUC(0-infinity)]
timeFrame: 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
measure: Plasma Pharmacokinetics of Radioactivity: Area Under the Concentration Time Curve From Time Zero to Infinity [AUC(0-infinity)]
timeFrame: 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
measure: Plasma Pharmacokinetics of LY2603618: Area Under the Concentration Time Curve From Time Zero to Time t [AUC(0-tlast)]
timeFrame: 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
measure: Plasma Pharmacokinetics of Radioactivity: Area Under the Concentration Time Curve From Time Zero to Time t [AUC(0-tlast)]
timeFrame: 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 96 hours post-dose
measure: Relative Abundance of LY2603618 and the Metabolites of LY2603618 in Urine
timeFrame: Day 1 through 7 days postdose
measure: Relative Abundance of LY2603618 and the Metabolites of LY2603618 in Feces
timeFrame: Day 1 through 7 days postdose
measure: The Number of Participants With a Tumor Response
timeFrame: Baseline through study completion [Cycle 5 (28 days/cycle) and 21-day safety follow-up]
Other outcomes:
Locations:
city: Bruderholz
country: Switzerland
facility: 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.
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon-Fri 9AM-5PM Eastern time (UTC/GMT- 5 hours, EST)
role: STUDY_DIRECTOR
References: