Phase 2 Study of Gemcitabine or Gemcitabine + Enzastaurin in Participants With 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.

Time frame: Randomization to the date of death from any cause up to 27.7 months

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

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

Time frame: Cycles 1 to 6, and post-treatment (up to 27.7 months)

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

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.

Time frame: Baseline through end of study up to 27.7 months

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

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).

Time frame: Time of response to PD or death from any cause up to 19.9 months

Population: 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.

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.

Time frame: Baseline through study completion (Up To 27.7 Months)

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

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.

Time frame: Randomization to measured progressive disease (PD) up to 19.9 months

Population: 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.

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.

Time frame: Randomization to measured PD or death from any cause up to 21.6 months

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

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.

Time frame: Beginning of treatment up to 27.7 months

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 and had data for overall response.

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.

Time frame: Randomization to date of death from any cause up to 27.7 months

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