Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Antineoplastic Agents

All Drugs and Chemicals

Gemcitabine

Antimetabolites

1200 milligrams (mg) loading dose then 500 mg, orally, daily, six 28-day cycles

enzastaurin

1000 milligrams/square meter (mg/m\^2), intravenously on Days 1, 8 and 15 per cycle, six 28-day cycles

gemcitabine

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

The purpose of this research study is to determine the effects and toxicity of gemcitabine alone or gemcitabine plus enzastaurin in participants with pancreatic cancer.

Phase 2 Study of Gemcitabine or Gemcitabine + Enzastaurin in Participants With Advanced or Metastatic Pancreatic Cancer

A Randomized, Open-Label Phase 2 Study of 2 Regimens, Gemcitabine Plus Enzastaurin and Single-Agent Gemcitabine, in Patients With Locally Advanced or Metastatic Pancreatic Cancer

OS was the duration from randomization to death. OS was censored at the last contact for participants who were alive, at the cut-off date.

Response rate was defined as percentage of responders (best study response recorded as CR or PR) from the qualified number of participants for tumor response analysis. Response defined using Response Evaluation Criteria In Solid Tumors (RECIST, v1.0) criteria: CR was disappearance of all target lesions for at least 4 weeks. PR was at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of LD.

Percentage of participants was calculated as: (The number of responders with CR or PR/ The number of participants qualified for tumor response analysis) × 100.

PFS was defined as the time from the date of randomization to the first date of documented progressive disease (PD) or death due to any cause, whichever occurred first. PFS was censored at the date of the last assessment visit for participants who were still alive at data cut-off and who had not had documented progressive disease. Participants who started a new treatment before progression were censored as of the date of the start of new treatment.

The duration of a complete response (CR) or partial response (PR) was defined, using the Response Evaluation Criteria in Solid Tumors (RECIST v1.0) criteria, as the time from first objective status assessment of CR or PR to the first time of disease progression or death as a result of any cause. Using the Response Evaluation Criteria in Solid Tumors (RECIST V1.0) criteria, CR was defined as the disappearance of all tumor lesions. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum of LD. Duration of response was censored at the date of the last assessment visit for responders who were still alive at data cut-off and had no documented progressive disease (PD).

FACT-Hep consists of 45 items in five subscales (1) physical well-being (PWB) score rage 0 -28; (2) social well-being (SWB) score range 0-28; (3) emotional well-being (EWB) score range 0-24; (4) functional well-being (FWB) score range 0-28; and (5) the hepatobiliary cancer subscale (HCS) Score range 0-72. The Trial Outcomes Index (TOI) is the sum of the PWB, FWB and Hep subscales with a scores range of 0 to 128. The Total FACT-Hep score was the sum of all questions with a scores range of 0 to 180. The Total FACT-G score was the sum of the 27 questions in the PWB, SFWB, EWB and FWB with a scores range of 0 to 108. The FACT-Hep Symptoms Index with 8 key questions and scores range of 0 to 32 from the Hep Subscale. Higher score in sub-score or total score indicates better QOL and better health state. Participants were classified as "Improved" if they had positive change from baseline, "Worsened" if they had negative change from baseline, and "Stable" otherwise.

OS was the duration from randomization to death from any cause. For participants who were alive at data cut-off, OS was censored at the last contact. Participants were categorized into 2 groups based on their steady state drug levels of Enzastaurin (total analyte=enzastaurin + LSN326020 \[metabolite\]): those participants below the median and those participants above the median \[2786.042 nanomoles per /liter (nmol/l)\]. The steady state drug levels and clinical outcomes were not evaluated for the Gemcitabine only treatment group.

The overall disease control rate was calculated as percent of participants with overall response of complete response (CR), partial response (PR) or stable disease (SD) over number of per-protocol population. Using the Response Evaluation Criteria in Solid Tumors (RECIST v1.0) criteria, CR: disappearance of all target and non-target lesions; PR: as at least a 30% decrease in sum of longest diameter (LD) of target lesions; progressive disease (PD) was defined as at least 20% increase in sum of LD of target lesions; SD: small changes that did not meet above criteria.

Participants were categorized into 2 groups based on their steady state drug levels of Enzastaurin (total analyte=enzastaurin + LSN326020 \[metabolite\]): participants below the median and participants above the median \[2754.521 nanomoles per liter (nmol/l)\].

The steady state drug levels and clinical outcomes were not evaluated for the Gemcitabine only group.

CA19-9 is a tumor biomarker which was measured in the blood to assess the effect of treatment with enzastaurin.

Clinically significant events were defined as SAEs and other non-serious adverse events (AEs). Participants who died due to progressive disease (PD), AEs while on treatment or died during the 30 day post-treatment are included. A summary of SAEs and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.

Eli Lilly and Company

Study-specific clinical outcomes due to progressive disease were not considered to be serious adverse events (SAEs) unless it was deemed related to study drug by the investigator.

Enzastaurin: 1200 milligrams (mg) administered orally (as three 400-mg doses) after a meal on Day 1, then 500 mg orally, daily (as five 100-mg tablets) after lunch on Days 2 to 28 in Cycle 1, then 500 mg orally, daily (as five 100-mg tablets) after lunch on Days 1 to 28 in Cycle 2 and later.

Gemcitabine: 1000 milligrams/square meter (mg/m\^2) administered intravenously on Days 1, 8 and 15 of each 28-day cycle.

Enzastaurin+Gemcitabine

Gemcitabine: 1000 mg/m\^2 administered intravenously on Days 1, 8 and 15 of each of each 28-day cycle.

Gemcitabine: 1000 mg/m\^2 administered intravenously on Days 1, 8 and 15 of each 28-day cycle.

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

White

Black or African American

Asian

Hispanic

Race/Ethnicity, Customized

United States

Region of Enrollment

0 - Fully Active

1 - Ambulatory, Restricted Strenuous Activity

2 - Ambulatory, No Work Activities

\[1\] ECOG is a scale of participants activity Status 0 - Fully Active

1. - Ambulatory, Restricted Strenuous Activity
2. - Ambulatory, No Work Activities

Eastern Cooperative Oncology Group (ECOG) Performance Status

Body Surface Area (BSA)

Stage IIA

Stage IIB

Stage III

Stage IV

Stage means how big the tumor is and how far it has spread. Stages range from 0 (not spread) to IV (spread throughout the body).

Stage IIA -The tumor is outside pancreas but not in large blood vessels or lymph nodes; Stage IIB: Cancer in or outside pancreas but not in large blood vessels; spread to nearby lymph nodes.

Stage III - The tumor is outside pancreas and spread to nearby large blood vessels or major nerves. May or may not have spread to nearby lymph nodes; not spread to distant sites.

Stage IV - the cancer has spread to other organs of the body such as the lung, brain, or liver.

Diagnosis Stage

Stage means how big the tumor is and how far it has spread. Stages range from 0 (not spread) to IV (spread throughout the body).

Stage IIB: Cancer in or outside pancreas but not in large blood vessels; spread to nearby lymph nodes.

Stage III - The tumor is outside pancreas and spread to nearby large blood vessels or major nerves. May or may not have spread to nearby lymph nodes; not spread to distant sites.

Stage IV - the cancer has spread to other organs of the body such as the lung, brain, or liver.

Current Stage

Intent-to-treat (ITT) population: All randomized participants.

Chief Medical Officer

Intent-to -treat (ITT) population: All randomized participants. Participants censored: Enzastaurin+Gemcitabine = 17; Gemcitabine = 11.

Overall Survival (OS)

Per Protocol Population: Randomized participants who had: 1) histological or cytological diagnosis of locally advanced (Stage II, III) or metastatic (Stage IV) adenocarcinoma of the pancreas; 2) no concurrent systemic chemotherapy; 3) presence of measurable disease at baseline; and 4) received at least 1 dose of study drug.

Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Response Rate)

Intent-to-treat (ITT) population: All randomized participants. Participants censored: Enzastaurin+Gemcitabine = 21; Gemcitabine = 10.

Progression Free Survival (PFS)

Participants in the Per Protocol population with a CR or PR: With histological or cytological diagnosis of locally advanced adenocarcinoma of the pancreas; no concurrent systemic chemotherapy; presence of measurable disease at baseline; and treatment with at least 1 dose of study drug. Censored: Enzastaurin+Gemcitabine = 1; Gemcitabine = 0.

Duration of Response

Physical well-being- Improved

Physical well-being- Stable

Physical well-being- Worsened

Social well-being- Improved

Social well-being- Stable

Social well-being- Worsened

Emotional well-being- Improved

Emotional well-being- Stable

Emotional well-being- Worsened

Functional well-being- Improved

Functional well-being- Stable

Functional well-being- Worsened

Hepatobiliary cancer subscale- Improved

Hepatobiliary cancer subscale- Stable

Hepatobiliary cancer subscale- Worsened

Total Outcome Index- Improved

Total outcome index- Stable

Total outcome index- Worsened

Total FACT-Hep score- Improved

Total FACT-Hep score- Stable

Total FACT-Hep score- Worsened

Total FACT-G-score- Improved

Total FACT-G-score- Stable

Total FACT-G-score- Worsened

FACT Hep Symptoms Index- Improved

FACT Hep Symptoms Index- Stable

FACT Hep Symptoms Index- Worsened

All randomized participants who received at least one dose of study drug and had data for FACT-Hep questionnaire.

Change in Scores From Baseline (Improved, Stable or Worsened) to End of Study in Functional Assessment of Cancer Therapy Hepatobiliary Version 4 ( FACT-Hep v.4) (Quality of Life (QOL))

Below median

Above median

All participants who received at least 1 dose of study drug. Participants censored: Below median = 4; Above median =4.

Relationship of Steady-State Drug Levels to Clinical Outcomes of Overall Survival (OS)

CR (Below median)

CR (Above median)

PR (Below median)

PR (Above median)

SD (Below median)

SD (Above median)

PD (Below median)

PD (Above median)

Disease Control (Below median)

Disease Control (Above median)

Randomized participants who had: 1) Histological or cytological diagnosis of locally advanced (Stage II, III) or metastatic (Stage IV) adenocarcinoma of the pancreas; 2) no concurrent systemic chemotherapy; 3) presence of measurable disease at baseline; and 4) received at least 1 dose of study drug and had data for overall response.

Relationship of Steady-state Drug Levels to Best Overall Response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) (Disease Control)

Cycle 1

Cycle 2

Cycle 3

Cycle 4

Cycle 5

Cycle 6

Post-treatment 1st visit

Post-treatment 2nd visit

Safety population: All randomized participants who received at least 1 dose of study drug.

Carbohydrate Antigen 19-9 (CA 19-9) Concentration in the Blood

Non-serious AEs

SAEs

Deaths due to PD

Deaths due to AEs

Deaths within 30-days after treatment

Safety population: All participants who received at least 1 dose of study drug.

Number of Participants Experiencing Serious Adverse Events (SAEs) and Adverse Events (AEs) (Toxicity)

Gemcitabine: 1000 milligrams/square meter (mg/m\^2) administered intravenously on Days 1, 8 and 15 of each 28-day cycle.

Spots Global Cancer Trial Database for Phase 2 Study of Gemcitabine or Gemcitabine + Enzastaurin in Participants With Advanced or Metastatic Pancreatic Cancer

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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