A Phase 1/Randomized Phase 2 Study to Evaluate LY2603618 in Combination with Gemcitabine in Patients with Pancreatic Cancer

Phase 2

Completed

Conditions: Pancreas adenocarcinoma
10014713

Registration Number: NL-OMON36787

Lead Sponsor: Eli Lilly

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 15

Inclusion Criteria

-Histological or cytological diagnosis of adenocarcinoma of the pancreas that is locally advanced (Stage II, III) or metastatic (Stage IV) and not amenable to resection with curative intent. Patients with previous radical surgery for pancreas cancer are eligible after progression is documented. If they received adjuvant chemotherapy or chemoradiotherapy with gemcitabine, they can be enrolled if the treatment was completed 6 months before or longer.;[3] Have measurable disease or non-measurable disease, defined according to RECIST (Protocol Attachment JMMC.5).;[4] Males or females at least 18 years of age.;[5] Have given written informed consent prior to any study-specific procedures.;[6] Have adequate organ function including:
* Hematologic: Absolute neutrophil count (ANC) *1.5 x 109/L platelets *100 x 109/L, and hemoglobin *9 g/dL.
* Hepatic: Bilirubin *1.5 times upper limits of normal (ULN), aspartate transaminase (AST) <2.5 times ULN, alanine transaminase (ALT) *2.5 times ULN. If the liver has tumor involvement, aspartate transaminase (AST) <5 times ULN and ALT equaling *5 times ULN are acceptable. Patients may have endoscopic or radiologic stenting to treat biliary obstructions. If so, then bilirubin must return to <1.5 x ULN and alkaline phosphatase (AP), aspartate transaminase (AST) <5 times ULN, ALT to *5 x ULN prior to enrollment.
* Renal: Serum creatinine within normal limits, *1.5 times ULN. If the patient is enrolled using the local lab, the same local lab must be used throughout the study for dosing decisions.;[7] Have a performance status of *2 on the Eastern Cooperative Oncology Group (ECOG) scale (refer to Protocol Attachment JMMC.6).;[8] Patients may have received previous adjuvant treatment with gemcitabine with or without radiotherapy for pancreas cancer. Adjuvant treatment must have finished at least 6 months before enrolling.;[9] Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures.;[10] Males and females with reproductive potential must agree to use medically approved contraceptive precautions during the trial until the patient*s physicians deems it safe to become pregnant or father a child.;[11] Females with child bearing potential must have had a negative urine pregnancy test *7 days prior to the first dose of study drug.;[13] Prior radiation therapy for treatment of cancer other than pancreatic is allowed to <25% of the bone marrow (Cristy and Eckerman 1987), 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.;[14] Baseline ECG QTc interval corrected by Bazett*s method (i.e., the QTc or sometimes referred to as QTcB) should be <450 msec for males and <470 msec for females.

Exclusion Criteria

-Are currently enrolled in, or discontinued within the last 28 days from, a clinical trial involving an off-label use of an investigational drug or device (other than the study drug used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.
-Have serious preexisting medical conditions or serious concomitant systemic disorders that would compromise the safety of the patient or his/her ability to complete the study, at the discretion of the investigator (for example, unstable angina pectoris or uncontrolled diabetes mellitus).
-Have symptomatic central nervous system malignancy or metastasis (screening not required).
-Have current active infection that would, in the opinion of the investigator, compromise the patient*s ability to tolerate therapy.
-Females who are pregnant or lactating.
-Have known positive test results in human immunodeficiency virus (HIV), hepatitis B surface antigen (HBSAg), or hepatitis C antibodies (HCAb). Testing is not required unless circumstances warrant confirmation.
-Endocrine pancreatic tumors or ampullary cancer.
-Have previously completed or withdrawn from this study or any other study investigating LY2603618 or any other Chk1 inhibitor.
-Have known allergy to gemcitabine or LY2603618 or any ingredient of gemcitabine or LY2603618.
-Has an abnormal ECG result that would put the patient at unnecessary risk in the opinion of the investigator.
-Have conduction abnormalities, ischemic changes such as prior Qwave myocardial infarction and/or marked ischemic ST and T wave, and arrhythmias such as persistent or paroxysmal ventricular or supraventricular arrhythmias, including atrial fibrillation.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Overall survival (OS) is the primary outcome of interest.<br /><br>Pharmacokinetic (PK) analyses will be conducted on patients who have received<br /><br>at least 1 dose of the study drug and have had samples collected.<br /><br><br /><br>All patients who receive at least 1 dose of study drug will be evaluated for<br /><br>safety and toxicity. The primary safety outcome will be to compare the<br /><br>incidence of AEs between the 2 treatment groups.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>The following secondary efficacy parameters will be summarized for each<br /><br>treatment group:<br /><br>* Progression-free survival (PFS)<br /><br>* Overall Response Rate (ORR)<br /><br>* Clinical benefit rate</p><br>