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A Study for Participants With Pancreatic Cancer

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ClinicalTrials.gov Identifier: NCT00839332
Recruitment Status : Completed
First Posted : February 9, 2009
Results First Posted : April 17, 2018
Last Update Posted : April 17, 2018
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

February 6, 2009
February 9, 2009
February 17, 2018
April 17, 2018
April 17, 2018
February 2009
February 2013   (Final data collection date for primary outcome measure)
  • Phase 1: Determine the Recommended Phase 2 Dose for LY2603618 When Administered After Gemcitabine [ Time Frame: Baseline through 18 months ]
    The recommended Phase 2 dose for LY2603618 when administered approximately 24 hours after gemcitabine was based on the maximum tolerated dose and achievement of predefined LY2603618 plasma systemic exposures targets (area under the LY2603618 plasma concentration versus time curve from time zero to infinity [AUC(0-inf)] >21,000 nanogram*hour/milliliter [ng*h/mL] and maximum LY2603618 plasma concentration [Cmax] >2000 nanograms/milliliter [ng/mL]).
  • Phase 2: Overall Survival (OS) [ Time Frame: Phase 2: Baseline to date of death ]
    Overall survival (OS) time is defined as the time from the date of randomization to the date of death from any cause. For participants not known to have died as of the data cut-off date, OS time was censored at the last contact date the participant was known to be alive prior to the cut-off date. OS was summarized using Kaplan-Meier estimates.
  • Phase 1: Determine the maximum tolerated dose for LY2603618 when administered after gemcitabine. [ Time Frame: Time of first dose until 28 days post dose ]
  • Phase 2: overall survival [ Time Frame: Baseline to date of death ]
Complete list of historical versions of study NCT00839332 on ClinicalTrials.gov Archive Site
  • Phase 1: Maximum Plasma Concentration (Cmax) of Gemcitabine, 2',2'-Difluorodeoxyuridine (dFdU), and LY2603618 [ Time Frame: Phase 1: LY2603618 - Predose and 0, 1, 3, 6, 24, 48, and 72 hours after the end of infusion on C1 /D2, C1 /D16, and C2 /D2. Gemcitabine - Predose and 0, 10, 30, 60, and 120 minutes after the end of infusion on C1 /D1, C1 /D15, and C2 /D1. ]
    Plasma samples for pharmacokinetic (PK) analysis were collected following IV infusion of each study drug. However, the dose-normalized PK analysis of gemcitabine and dFdU were not reported because the gemcitabine and dFdU plasma concentration data generated for all participants with PK samples collected in this study were withdrawn (invalidated) as a result of the failure of the Incurred Sample Reanalysis (ISR) for both gemcitabine and dFdU. Therefore, only the LY2603618 plasma Cmax values are reported for each LY2603618 dose level on Cycle (C) 1 /Day (D) 1, Cycle 1 /Day 16, and Cycle 2 /Day 2. The number of PK observations (n) used in the analysis is presented for each dose level and time point.
  • Phase 2: Maximum Plasma Concentration (Cmax) of Gemcitabine, dFdU, and LY2603618 [ Time Frame: Phase 2: LY2603618 - Predose and 0, 1, 3, and 24 hours after the end of infusion on Days 2 and 16 of Cycle 1. Gemcitabine - Predose and 0, 10, 60, and 120 minutes after the end of infusion on Days 1 and 15 of Cycle 1. ]
    Plasma samples for PK analysis were collected following IV infusion of each study drug. However, the dose-normalized PK analysis of gemcitabine and dFdU were not reported because the gemcitabine and dFdU plasma concentration data generated for all participants with PK samples collected in this study were withdrawn (invalidated) as a result of the failure of the Incurred Sample Reanalysis (ISR) for both gemcitabine and dFdU. Therefore, only the LY2603618 plasma Cmax values are reported at the 230 mg LY2603618 dose level on Cycle 1 /Day 1, Cycle 1 /Day 16, and Cycle 2 /Day 2. The number of PK observations (n) used in the analysis is presented for each time point.
  • Phase 1: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618 [ Time Frame: Phase 1: LY2603618 - Predose and 0, 1, 3, 6, 24, 48, and 72 hours after the end of infusion on C1 /D2, C1 /D16, and C2 /D2. Gemcitabine - Predose and 0, 10, 30, 60, and 120 minutes after the end of infusion on C1 /D1, C1 /D15, and C2 /D1. ]
    Plasma samples for PK analysis were collected following IV infusion of each study drug. However, the dose-normalized PK analysis of gemcitabine and dFdU were not reported because the gemcitabine plasma and dFdU concentration data generated for all participants with PK samples collected in this study were withdrawn (invalidated) as a result of the failure of the Incurred Sample Reanalysis (ISR) for both gemcitabine and dFdU. Therefore, only LY2603618 plasma AUC from time zero to 24 hours (AUC[0-24]), AUC from time zero to the last time point with a measurable concentration (AUC[0-tlast]), and AUC from time zero to infinity (AUC[0-inf]) values are reported for each LY2603618 dose level on Cycle 1 /Day 1, Cycle 1 /Day 16, and Cycle 2 /Day 2. The number of PK observations (n) used in the analysis is presented for each dose level and time point.
  • Phase 2: Area Under the Plasma Concentration Versus Time Curve (AUC) of Gemcitabine, dFdU, and LY2603618 [ Time Frame: Phase 2: LY2603618 - Predose and 0, 1, 3, and 24 hours after the end of infusion on Days 2 and 16 of Cycle 1. Gemcitabine - Predose and 0, 10, 60, and 120 minutes after the end of infusion on Days 1 and 15 of Cycle 1. ]
    Plasma samples for PK analysis were collected following IV infusion of each study drug. However, the dose-normalized PK analysis of gemcitabine and dFdU were not reported because the gemcitabine and dFdU plasma concentration data generated for all participants with PK samples collected in this study were withdrawn (invalidated) as a result of the failure of the Incurred Sample Reanalysis (ISR) for both gemcitabine and dFdU. Therefore, only the LY2603618 plasma AUC(0-24), AUC(0-tlast), and AUC(0-inf) values are reported for the 230 mg LY2603618 dose on Cycle 1 /Day 1, Cycle 1 /Day 16, and Cycle 2 /Day 2. The number of PK observations (n) used in the analysis is presented for each time point.
  • Phase 2: Progression-free Survival (PFS) [ Time Frame: Phase 2: Baseline to measured progressive disease or date of death from any cause ]
    Progression-free survival (PFS) time was defined as the time from the date of randomization to the first date of progressive disease (symptomatic or objective) or death due to any cause, whichever occurred first. For participants who were not known to have died or progressed as of the data-inclusion cutoff date, PFS time was censored at the date of the last objective progression-free disease assessment prior to the date of any subsequent systematic anticancer therapy. PFS was summarized using Kaplan-Meier estimates.
  • Phase 2: Overall Response Rate [ Time Frame: Phase 2: Baseline to measured progressive disease or date of death from any cause ]
    Overall response rate is the best response of complete response (CR) or partial response (PR) as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1) guidelines. CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of not-target lesions or appearance of new lesions. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants with at least 1 measurable lesion, multiplied by 100.
  • Phase 2: Clinical Benefit Rate [ Time Frame: Phase 2: Baseline to measured progressive disease or date of death from any cause ]
    Clinical benefit rate is the best response CR, PR, or stable disease (SD) as classified by the investigators according to the RECIST v1.1 guidelines. CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of not-target lesions or appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameter since treatment started. Overall response rate is calculated as a total number of participants with CR, PR, or SD divided by the total number of participants with at least 1 measurable lesion, multiplied by 100.
  • Phase 2: Duration of Response [ Time Frame: Phase 2. Baseline to measured progressive disease or date of death from any cause ]
    Duration of response was defined as the time from the first observation of complete response (CR) or partial response (PR) to the first observation of progressive disease or death from any cause. For participants who were not known to have died as of the data-inclusion cut-off date and who do not have progressive disease, the duration was censored at the date of the last objective progression-free disease assessment prior to the date of any subsequent anticancer therapy (systemic, radiologic, or surgery). Participants were also censored at the last valid assessment prior to missing more than 1 consecutive scheduled assessment. Duration of response was summarized using Kaplan-Meier estimates.
  • Phase 1: Electrocardiogram QTc Prolongation [ Time Frame: Phase 1: Days 2 and 16 of Cycle 1 ]
    The QT interval is a measure of the time between the start of the Q wave and the end of the T wave. Twelve-lead electrocardiogram (ECG) data was used to calculate the corrected QT (QTc) based on Fridericia's formula (QTc=QT/RR^0.33, where RR is the interval between two R waves). For each participant, changes in QTc were calculated by subtracting the reading taken before LY2603618 administration from the reading taken after LY2603618 administration on Days 2 and 16 during Cycle 1. The number of participants in which the change in QTc was <=30 milliseconds (msec), >30-60 msec, or >60 msec is presented by dose group and overall.
  • Phase 2: Electrocardiogram QTc Prolongation [ Time Frame: Phase 2: Days 2 and 16 of Cycle 1 ]
    The QT interval is a measure of the time between the start of the Q wave and the end of the T wave. Twelve-lead ECG data was used to calculate QTc based on Fridericia's formula (QTc=QT/RR^0.33, where RR is the interval between two R waves). For each participant, changes in QTc were calculated by subtracting the reading taken before LY2603618 administration from the reading taken after LY2603618 administration on Days 2 and 16 during Cycle 1. The number of participants in which the change in QTc was <=30 milliseconds (msec), >30-60 msec, or >60 msec is presented.
  • Cmax of gemcitabine and LY2603618 [ Time Frame: Phase 1: During cycles 1 and 2 Phase 2: During cycle 1 ]
  • Overall tumor response rate [ Time Frame: baseline to measured progressive disease ]
  • Electrocardiogram QTc prolongation [ Time Frame: Baseline and during Cycle 1 of both Phase 1 and Phase 2 for patients receiving LY2603618 ]
  • Time to disease progression [ Time Frame: Baseline to objective progression ]
  • Response rate in tumor size at 8 weeks and the relationship with overall survival [ Time Frame: Baseline to date of confirmed response and date of death from any cause ]
  • Time to treatment failure [ Time Frame: baseline to time of discontinuing gemcitabine and/or LY2603618 or baseline to time of starting of new therapy after discontinuing study treatment ]
  • AUC of gemcitabine and LY2603618 [ Time Frame: Phase 1: During cycles 1 and 2 Phase 2: During cycle 1 ]
Number of Deaths During the Phase 1 Post-study Period [ Time Frame: Phase 1: Time of last dose of study drug through the end of the follow-up period ]
The number of participants who died during the post-study period of Phase 1 does not include the outcomes for the 4 participants who died while on treatment during Phase 2 as captured in the Participant Flow Table. A summary of serious and other non‐serious adverse events regardless of causality is located in the Reported Adverse Events module.
Not Provided
 
A Study for Participants With Pancreatic Cancer
A Phase 1/Randomized Phase 2 Study to Evaluate LY2603618 in Combination With Gemcitabine in Patients With Pancreatic Cancer
The purpose of the Phase 1 portion of this study was to determine the dose of LY2603618 that can be safely administered 24 hours after gemcitabine treatment. This dose was then used for the Phase 2 portion of the study. The Phase 2 portion of the study evaluated whether LY2603618, when administered 24 hours after gemcitabine therapy, was an effective treatment for participants with pancreatic cancer.
Phase 1 included a dose escalation of LY2603618 doses from 70 milligrams/meter squared (mg/m^2) to 250 mg/m^2 divided into 5 cohorts. Each participant was assigned to a single cohort with no intra-participant dose escalation. Phase 1 also included an expansion cohort where participants received a flat dose of 200 or 230 mg LY2603618. Participants received gemcitabine on Days 1, 8, and 15, followed by LY2603618 on Days 2, 9, and 16 of each 28-day cycle. The purpose of the Phase 1 portion was to determine the maximum tolerated LY2603618 dose to be carried into the Phase 2 portion of the study.
Interventional
Phase 1
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Pancreatic Neoplasms
  • Drug: LY2603618
  • Drug: Gemcitabine
    Other Names:
    • Gemzar
    • LY188011
  • Experimental: LY2603618 + Gemcitabine

    Participants participated in Phase 1 or 2.

    LY2603618 (Phase 1): 70 to 250 milligrams/meter squared (mg/m^2) LY2603618 as a 1-hour continuous intravenous (IV) infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression (DP). Participants received LY2603618 as part of the dose escalation cohort (dose of 70, 105, 150, 200, or 250 mg/m^2) or the expansion cohort (flat dose of 200 mg or 230 mg).

    LY2603618 (Phase 2): 230 mg LY2603618 as a 1-hour continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until DP.

    Gemcitabine (Phase 1 and 2): 1000 mg/m^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until DP. Participants received gemcitabine 24 hours prior to LY2603618 administration.

    Interventions:
    • Drug: LY2603618
    • Drug: Gemcitabine
  • Active Comparator: Gemcitabine

    Participants participated in Phase 2 only.

    Gemcitabine (Phase 2): 1000 mg/m^2 gemcitabine as a 30-minute continuous IV infusion once per week for 3 weeks, followed by 1 week of rest. This 28-day cycle was repeated for a minimum of 2 cycles and/or until disease progression.

    Intervention: Drug: Gemcitabine
Laquente B, Lopez-Martin J, Richards D, Illerhaus G, Chang DZ, Kim G, Stella P, Richel D, Szcylik C, Cascinu S, Frassineti GL, Ciuleanu T, Hurt K, Hynes S, Lin J, Lin AB, Von Hoff D, Calvo E. A phase II study to evaluate LY2603618 in combination with gemcitabine in pancreatic cancer patients. BMC Cancer. 2017 Feb 15;17(1):137. doi: 10.1186/s12885-017-3131-x.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
157
125
December 2013
February 2013   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Diagnosed with cancer that is metastatic and/or advanced during Phase 1
  • Diagnosed with pancreatic cancer that is metastatic and not amenable to surgery
  • Must be at least 18 years of age
  • Adequate hematological, liver, and renal functions
  • Eastern Cooperative Oncology Group (ECOG) status of 0 to 2

Exclusion Criteria:

  • Known hypersensitivity to gemcitabine
  • Pregnant or lactating females or refusal to use medically approved contraceptive precautions
  • Had prior treatment with radiotherapy involving more than 25% of marrow producing area
  • Have received treatment in the last 30 days with a drug which has not received regulatory approval for any indication at the time of study entry
Sexes Eligible for Study: All
18 Years to 85 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Germany,   Italy,   Netherlands,   Romania,   Spain,   United States
Poland,   Slovakia
 
NCT00839332
12096
I2I-MC-JMMC ( Other Identifier: Eli Lilly and Company )
Yes
Not Provided
Not Provided
Eli Lilly and Company
Eli Lilly and Company
Not Provided
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
Eli Lilly and Company
March 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP