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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01296568
First received: February 14, 2011
Last updated: April 26, 2012
Last verified: April 2012
  Purpose

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 [14C]LY2603618 dose, patients will be allowed to continue to receive continued access to LY2603618 in combination with pemetrexed or gemcitabine as outpatients.


Condition Intervention Phase
Advanced Cancer
Drug: LY2603618
Drug: Pemetrexed
Drug: Gemcitabine
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Disposition of [14C]LY2603618 Following Intravenous Administration in Patients With Advanced and/or Metastatic Solid Tumors

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Urinary and fecal excretion of LY2603618 radioactivity over time expressed as a percentage of the total radioactive dose administered [ Time Frame: 7 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Plasma pharmacokinetics of LY2603618 and radioactivity (Cmax) [ Time Frame: 7 days ] [ Designated as safety issue: No ]
  • Plasma pharmacokinetics of LY2603618 and radioactivity AUC(0-infinity) [ Time Frame: 7 days ] [ Designated as safety issue: No ]
  • Plasma pharmacokinetics of LY2603618 and radioactivity AUC(0-Tlast) [ Time Frame: 7 days ] [ Designated as safety issue: No ]
  • Relative abundance of LY2603618 and the metabolites of LY2603618 in urine, and feces [ Time Frame: 7 days ] [ Designated as safety issue: No ]
  • The number of participants with a tumor response [ Time Frame: Baseline to study completion ] [ Designated as safety issue: No ]

Estimated Enrollment: 12
Study Start Date: February 2011
Study Completion Date: February 2012
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LY2603618

Single 250 mg intravenous dose of LY2603618 containing [14C] LY2603618.

After the completion of a minimum 7 day wash out period, patients may receive additional doses of LY2603618 in combination as follows:

  • Gemcitabine 1000 mg/m2 on Days 1, 8, and 15 with 230 mg LY2603618 being administered on days 2, 9 and 16 of a 28-day cycle OR
  • Pemetrexed 500 mg/m2 on day 1 and 275 mg LY2603618 on day 2 of a 21-day cycle

Patients 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.

Drug: LY2603618
Administered intravenously
Drug: Pemetrexed
Administered intravenously
Other Names:
  • LY231514
  • Alimta
Drug: Gemcitabine
Administered intravenously
Other Names:
  • LY188011
  • Gemzar

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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: Patients who have had progressive disease after receiving pemetrexed for metastatic disease are excluded from receiving the combination with pemetrexed during the safety extension study. Patients 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 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 patient 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 patient 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 patients 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). Patients 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 HIV or viral (A, B, or C) hepatitis (screening is not required)
  • Have a QTc interval of >500 msec on the screening electrocardiogram (ECG)
  • Have electrocardiogram (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 patient 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 mSv.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01296568

Locations
Switzerland
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, Switzerland, 4101
Sponsors and Collaborators
Eli Lilly and Company
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
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01296568     History of Changes
Other Study ID Numbers: 13525, I2I-MC-JMMH
Study First Received: February 14, 2011
Last Updated: April 26, 2012
Health Authority: United States: Food and Drug Administration
Switzerland: Swissmedic

Keywords provided by Eli Lilly and Company:
metastatic solid tumors
Malignant/M-Neoplasm
Pancreas NOS
Absorption
Distribution
Metabolism
Excretion
Mass balance
Metabolic profile
Radiolabeled study

Additional relevant MeSH terms:
Neoplasms
Gemcitabine
Pemetrexed
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Folic Acid Antagonists

ClinicalTrials.gov processed this record on July 23, 2014