Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of Ramucirumab (LY3009806) or Merestinib (LY2801653) in Advanced or Metastatic Biliary Tract Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02711553
Recruitment Status : Active, not recruiting
First Posted : March 17, 2016
Results First Posted : February 26, 2021
Last Update Posted : February 26, 2021
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Brief Summary:
The main purpose of this study is to evaluate the efficacy and safety of ramucirumab or merestinib or placebo plus cisplatin and gemcitabine in participants with advanced or metastatic biliary tract cancer.

Condition or disease Intervention/treatment Phase
Biliary Tract Cancer Metastatic Cancer Advanced Cancer Drug: Ramucirumab Drug: Merestinib Drug: Cisplatin Drug: Gemcitabine Drug: Placebo Oral Drug: Placebo IV Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 309 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Randomized, Double-Blind, Phase 2 Study of Ramucirumab or Merestinib or Placebo Plus Cisplatin and Gemcitabine as First-Line Treatment in Patients With Advanced or Metastatic Biliary Tract Cancer
Actual Study Start Date : May 19, 2016
Actual Primary Completion Date : February 16, 2018
Estimated Study Completion Date : December 31, 2021


Arm Intervention/treatment
Experimental: 8 mg/kg Ramucirumab + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine
Participants received 8 mg/kg ramucirumab plus 25 mg/square meter (mg/m²) cisplatin and 1000 mg/m² gemcitabine intravenously (IV) on days 1 and 8, every 21 days (1 cycle). Participants may continue on study drug for up to 8 cycles (for cisplatin and gemcitabine therapy) or until disease progression, unacceptable toxicity, or other withdrawal criterion is met (for ramucirumab therapy).
Drug: Ramucirumab
Administered IV
Other Name: LY3009806

Drug: Cisplatin
Administered IV

Drug: Gemcitabine
Administered IV
Other Name: LY188011

Placebo Comparator: Placebo IV + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine
Participants received placebo (indistinguishable and equivalent volume to ramucirumab) plus 25 mg/m² cisplatin and 1000 mg/m² gemcitabine IV on days 1 and 8, every 21 days (1 cycle). Participants may continue on study drug for up to 8 cycles (for cisplatin and gemcitabine therapy) or until disease progression, unacceptable toxicity, or other withdrawal criterion is met (for placebo therapy).
Drug: Cisplatin
Administered IV

Drug: Gemcitabine
Administered IV
Other Name: LY188011

Drug: Placebo IV
Administered IV

Experimental: 80 mg Merestinib + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine
Participants received 80 mg merestinib orally each day, plus 25 mg/m² cisplatin and 1000 mg/m² gemcitabine IV on Days 1 and 8, every 21 days (1 cycle). Participants may continue on study drug for up to 8 cycles (for cisplatin and gemcitabine therapy) or until disease progression, unacceptable toxicity, or other withdrawal criterion is met (for merestinib therapy).
Drug: Merestinib
Administered orally
Other Name: LY2801653

Drug: Cisplatin
Administered IV

Drug: Gemcitabine
Administered IV
Other Name: LY188011

Placebo Comparator: Placebo Oral + 25 mg/m² Cisplatin + 1000 mg/m² Gemcitabine
Participants received placebo (indistinguishable to merestinib) orally each day, plus 25 mg/m² cisplatin and 1000 mg/m² gemcitabine IV on Days 1 and 8, every 21 days. Participants may continue on study drug for up to 8 cycles (for cisplatin and gemcitabine therapy) or until disease progression, unacceptable toxicity, or other withdrawal criterion is met (for placebo therapy).
Drug: Cisplatin
Administered IV

Drug: Gemcitabine
Administered IV
Other Name: LY188011

Drug: Placebo Oral
Administered orally




Primary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: Randomization to Progressive Disease or Death from Any Cause (Up To 20 Months) ]
    PFS time was measured from the date of randomization until the first radiographic documentation of progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or death from any cause. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of first dose, regardless of whether or not objectively determined disease progression or death has been observed for the participant. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date.


Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Randomization to Date of Death from Any Cause (Up To 21 Months) ]
    OS defined as the time from from randomization to the date of death due to any cause. For each participant who is not known to have died as of the data-inclusion cutoff date for overall survival analysis, OS time was censored on the last date the participant is known to be alive.

  2. Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR) [ Time Frame: Randomization to Disease Progression (Up To 20 Months) ]
    ORR was the number of participants who achieve a best overall response of CR or PR divided by the total number of participants randomized to the corresponding treatment arm as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

  3. Percentage of Participants With a Best Overall Response of CR, PR, or Stable Disease (SD): Disease Control Rate (DCR) [ Time Frame: Randomization to Disease Progression (Up To 20 Months) ]
    Disease Control Rate (DCR) was the number of participants who achieve a best overall response of CR, PR, or SD divided by the total number of participants randomized to the corresponding treatment arm as per RECIST v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

  4. Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab [ Time Frame: C1 D8, C2 D1, C3 D1, C4 D1,C5 D1,C7 D1, C9 D1 and C13 D1: Within 3 days Prior to Infusion(PTI) ]
    PK was determined by the minimum observed plasma concentration (Cmin). 1 Cycle (C) = 21 days (D).

  5. PK: Plasma Concentration of Merestinib [ Time Frame: C1 D8; C2 D1; C4 D1; C6 D1; C8 D1; C2 D8; C4 D8; C6 D8; C8 D8: Morning ]
    PK was presented through graphical overlay comparison versus historic data. No numerical summary of data was intended or produced.

  6. Number of Participants With Treatment-Emergent Anti-Ramucirumab Antibodies [ Time Frame: Predose Cycle 1 Day 1 through Follow Up (Approximately 48 Months) ]
    Number of participants with positive treatment emergent anti-ramucirumab antibodies was summarized by treatment group.

  7. Change From Baseline in Functional Assessment of Cancer Therapy Hepatobiliary Questionnaire (FACT-Hep) [ Time Frame: Baseline, Follow Up (Approximately 48 Months) ]
    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.

  8. Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) [ Time Frame: Baseline, Follow Up (Approximately 48 Months) ]
    The EQ-5D-5L is a standardized instrument used to measure self-reported health status of the participants. It consists of 5 health dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). There are 5 response levels (no problems, slight problems, moderate problems, severe problems, and extreme problems/unable to), ranging from 1 to 5 (good to bad). Dimension responses were converted to an index score using UK weights. The index scores were anchored on full health (1.0) to dead (0) with negative values assigned to health states considered worse than death.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Have an Eastern Cooperative Oncology Group performance status of 0 or 1.
  • Have a histologically or cytologically confirmed diagnosis of non-resectable, recurrent, or metastatic biliary tract adenocarcinoma (intrahepatic or extrahepatic cholangiocarcinoma, gallbladder cancer, or Ampulla of Vater) .
  • Have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST).
  • Have adequate biliary drainage.
  • Have adequate organ function.
  • Males and females are sterile, postmenopausal, or compliant with a highly effective contraceptive method.
  • Female participants of childbearing potential must have a negative serum pregnancy test within 7 days prior to first dose.
  • Are willing to provide blood/serum/plasma and tumor tissue samples for research purposes. Submission of blood/serum/plasma and tumor tissue samples is mandatory for participation in this study, unless restricted per local regulations.

Exclusion Criteria:

  • Previous systemic therapy for locally advanced or metastatic disease is not allowed.
  • Have a history of or have current hepatic encephalopathy of any grade, or ascites of Grade >1, or cirrhosis with Child-Pugh Stage B or higher.
  • Have ongoing or recent (≤6 months) hepatorenal syndrome.
  • Have had a major surgical procedure or significant traumatic injury including nonhealing wound, peptic ulcer, or bone fracture ≤28 days prior to randomization.
  • Anticipate having a major surgical procedure during the course of the study.
  • Has documented brain metastases, leptomeningeal disease, or uncontrolled spinal cord compression.
  • Within 6 months prior to randomization, have had any arterial thrombotic event, including myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack.
  • Have an uncontrolled arterial hypertension with systolic blood pressure ≥150 or diastolic blood pressure ≥90 millimeters of mercury (mm Hg) despite standard medical management.
  • Have a previous malignancy within 5 years of study entry or a concurrent malignancy.
  • Have a history of gastrointestinal perforation and/or fistulae within 6 months prior to randomization.
  • Have a known allergy or hypersensitivity reaction to any of the treatment components.
  • Have a history of uncontrolled hereditary or acquired thrombotic disorder.
  • Have uncontrolled metabolic disorders or other nonmalignant organ or systemic diseases or secondary effects of cancer that induce a high medical risk and/or make assessment of survival uncertain.
  • Have mixed hepatocellular biliary tract cancer histology.
  • Have a corrected QT interval >470 milliseconds as calculated by the Fridericia equation.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02711553


Locations
Show Show 92 study locations
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Layout table for investigator information
Study Director: 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) Eli Lilly and Company
  Study Documents (Full-Text)

Documents provided by Eli Lilly and Company:
Study Protocol  [PDF] March 30, 2016
Statistical Analysis Plan  [PDF] March 19, 2018

Additional Information:
Layout table for additonal information
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT02711553    
Other Study ID Numbers: 16329
I3O-MC-JSBF ( Other Identifier: Eli Lilly and Company )
2015-004699-31 ( EudraCT Number )
First Posted: March 17, 2016    Key Record Dates
Results First Posted: February 26, 2021
Last Update Posted: February 26, 2021
Last Verified: August 15, 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
URL: https://vivli.org/
Additional relevant MeSH terms:
Layout table for MeSH terms
Biliary Tract Neoplasms
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Biliary Tract Diseases
Digestive System Diseases
Gemcitabine
Cisplatin
Ramucirumab
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs