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A Study of Paclitaxel With or Without Ramucirumab (IMC-1211B) in Metastatic Gastric Adenocarcinoma (RAINBOW)

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: NCT01170663
Recruitment Status : Completed
First Posted : July 27, 2010
Results First Posted : July 31, 2014
Last Update Posted : September 18, 2019
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Tracking Information
First Submitted Date  ICMJE July 21, 2010
First Posted Date  ICMJE July 27, 2010
Results First Submitted Date  ICMJE July 1, 2014
Results First Posted Date  ICMJE July 31, 2014
Last Update Posted Date September 18, 2019
Study Start Date  ICMJE December 2010
Actual Primary Completion Date July 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 1, 2014)
Overall Survival Time (OS) [ Time Frame: Randomization up to 27.5 months ]
OS time was measured from date of randomization to date of death from any cause. Participants who were not known to have died on or before the date of data cut-off, OS data was censored on the last date (on or before the cut-off date) the participant was known to be alive.
Original Primary Outcome Measures  ICMJE
 (submitted: July 26, 2010)
Overall Survival Time (OS) [ Time Frame: 32 months ]
Randomization to date of death from any cause
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 17, 2018)
  • Progression-Free Survival (PFS) [ Time Frame: Randomization up to 22.2 months ]
    PFS was measured from date of randomization to first radiographically documented progressive disease (PD) or death due to any cause. PD defined using Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1) as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of at least 5 mm. Participants who had no baseline or post baseline radiological tumor assessment were censored at date of randomization. Participants who had no tumor progression or death within 2 scan intervals following the last assessment were censored at the date of last radiographic tumor assessment. Participants who began new anticancer treatment and had no tumor progression were censored at date of assessment prior to initiation of new therapy. Participants lost to follow-up or withdrew consent were censored at the date of their last assessment.
  • Time to Progressive Disease (TTP) [ Time Frame: Baseline up to 22.2 months ]
    TTP was defined as the time from randomization until date of radiographic progression using RECIST v1.1 criteria. PD was defined as having a ≥20% increase in sum of longest diameter (LD) of target lesions and at minimum 5 millimeters (mm) increase above nadir. Participants who did not progress or were lost to follow-up were censored at the date of last tumor assessment. Participants who had no baseline tumor assessment or no post baseline assessment and no death reported with 2 scan intervals post randomization were censored at date of randomization. Participants with no progression and not died within 2 scan intervals after last assessment were censored at date of last tumor assessment. Participants with no post baseline assessment or tumor progression but death reported within 2 scan intervals after randomization were censored at date of death.
  • Best Overall Response (BOR) of Complete Response (CR), Partial Response (PR), Stable Disease (SD) or PD [ Time Frame: Randomization up to 22.2 months ]
    BOR was defined as the best response across all time points from randomization until radiologically confirmed PD using RECIST, v1.1 criteria. CR was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm and normalization of tumor marker level of non-target lesions. PR was defined as having a ≥30% decrease in sum of LD of target lesions. PD was defined as having a ≥20% increase in sum of LD of target lesions and ≥5 mm increase above nadir. SD was defined as small changes that did not meet above criteria.
  • Percentage of Participants With CR or PR (Objective Response Rate [ORR]) [ Time Frame: Randomization up to 22.2 months ]
    ORR was the percentage of participants who had CR or PR defined using RECIST v1.1 criteria. CR was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm and normalization of tumor marker level of non-target lesions. PR was defined as having a ≥30% decrease in sum of LD of target lesions. Percentage of participants calculated as: (number of participants with CR + PR)/(total number of participants)*100.
  • Percentage of Participants With Anti-Ramucirumab Antibodies (Serum Anti-Ramucirumab Antibody Assessment )(Immunogenicity) [ Time Frame: Prior to and after ramucirumab (IMC-1121B) infusion: Day 1 Cycles 1, 2 and 3 (28-day cycles) Doses 1, 4, 7 and 30-37 days after last dose of study therapy up to 103 weeks ]
    Participants who developed treatment-emergent antibody responses to Ramucirumab (IMC-1121B) after baseline.
  • Maximum Concentration (Cmax) After First Ramucirumab (IMC-1211B) Infusion [ Time Frame: Cycle 1, Day 1, 1 hour post end of infusion (28-day cycles) ]
  • Cmax After 4th Ramucirumab (IMC-1211B) Infusion [ Time Frame: Cycle 2, Day 15 1 hour post end of infusion (28-day cycles) ]
  • Cmax After 7th Ramucirumab (IMC-1211B) Infusion [ Time Frame: Cycle 4, Day 1, 1 hour post end of infusion (28-day cycles) ]
  • Minimum Concentration (Cmin) Prior to First Ramucirumab (IMC-1211B) Infusion [ Time Frame: Cycle 1, Day 1 predose (28-day cycles) ]
    This outcome measure was included in error as the time point was before ramucirumab (IMC-1211B) was administered. Cmin was not analyzed.
  • Cmin Prior to 4th Ramucirumab (IMC-1211B) Infusion [ Time Frame: Cycle 2, Day 15 (28-day cycle) ]
  • Cmin Prior to 7th Ramucirumab (IMC-1211B) Infusion [ Time Frame: Cycle 4, Day 1 (28-day cycles) ]
  • Change From Baseline to End of Therapy in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life: Questionnaire (QLQ-C30) in Global Health Status [ Time Frame: Baseline, end of therapy (up to 103 weeks) ]
    EORTC QLQ-C30 v3.0 is a 30-item, self-administered questionnaire with multidimensional scales assessing 15 domains (5 functional domains [physical, role, cognitive, emotional, and social], 9 symptom scales [fatigue, pain, nausea and vomiting, dyspnea, loss of appetite, insomnia, constipation and diarrhea, and financial difficulties] and global health status scale). 28 questions assessed on a 1 (not at all) to 4 (very much) scale and the remaining 2 questions used a 1 (poor) to 7 (excellent) scale. A linear transformation was applied to standardize the raw scores to range between 0 and 100 per developer guidelines. For the functional domains and global health status scale, higher scores represent a better level of functioning. For symptoms scales, higher scores represented a greater degree of symptoms.
  • Change From Baseline to End of Therapy in European Quality of Life Questionnaire-5 Dimension (EuroQol EQ-5D) Index Score [ Time Frame: Baseline, end of therapy (up to 103 weeks) ]
    The EQ-5D is a generic, multidimensional, health status instrument. The profile allowed participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood using a 3-level scale [1 (no problem), 2 (some problems), and 3 (major problems)]. These combinations of responses were converted into a weighted health-state Index Score according to the United Kingdom (UK) population-based algorithm. The possible values for the Index Score ranged from -0.59 (severe problems in all 5 dimensions) to 1.0 (no problem in any dimension). A negative change indicated a worsening of the participant's health status.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 26, 2010)
  • Progression-free survival (PFS) [ Time Frame: 32 months ]
    Radiographic assessment: Time from randomization to the first radiographic documented PD or death
  • Time to progressive disease (TTP) [ Time Frame: 32 months ]
    Time from Pretreatment, every 6 weeks after first infusion until first radiographic progressive disease (PD)
  • Best overall response (BOR) [ Time Frame: 32 months ]
    Pretreatment, every 6 weeks after first infusion until progressive disease (PD) will be determined using the RECIST (version1.1) guidelines
  • Objective response rate (ORR) [ Time Frame: 32 months ]
    Pretreatment, every 6 weeks after first infusion until progressive disease (PD); calculated as the number of patients who achieved a BOR of complete response (CR) or partial response (PR), divided by the total number of patients randomized
  • Serum Anti-Ramucirumab Antibody Assessment [ Time Frame: 32 months ]
    Prior to (within Pretreatment period) 1st ramucirumab infusion, prior to 4th ramucirumab infusion ( ~ week 6 after 1st dose), prior to 7th ramucirumab infusion (~ week 12 after first dose) and 30 - 37 days after last dose of therapy
  • Maximum concentration (Cmax) (ramucirumab + placebo) [ Time Frame: Cycle 1, Day 1 ]
    Prior to (within Pretreatment period) 1st ramucirumab infusion, prior to 4th ramucirumab infusion ( ~ week 6 after 1st dose), prior to 7th ramucirumab infusion (~ week 12 after first dose) and 30 - 37 days after last dose of therapy
  • Maximum concentration (Cmax) (ramucirumab + placebo) [ Time Frame: Cycle 2, Day 1 ]
    Prior to (within Pretreatment period) 1st ramucirumab infusion, prior to 4th ramucirumab infusion ( ~ week 6 after 1st dose), prior to 7th ramucirumab infusion (~ week 12 after first dose) and 30 - 37 days after last dose of therapy
  • Maximum concentration (Cmax) (ramucirumab + placebo) [ Time Frame: Cycle 4, Day 1 ]
    Prior to (within Pretreatment period) 1st ramucirumab infusion, prior to 4th ramucirumab infusion ( ~ week 6 after 1st dose), prior to 7th ramucirumab infusion (~ week 12 after first dose) and 30 - 37 days after last dose of therapy
  • Maximum concentration (Cmin) (ramucirumab + placebo) [ Time Frame: Cycle 1, Day 1 ]
    Prior to (within Pretreatment period) 1st ramucirumab infusion, prior to 4th ramucirumab infusion ( ~ week 6 after 1st dose), prior to 7th ramucirumab infusion (~ week 12 after first dose) and 30 - 37 days after last dose of therapy
  • Maximum concentration (Cmin) (ramucirumab + placebo) [ Time Frame: Cycle 2, Day 1 ]
    Prior to (within Pretreatment period) 1st ramucirumab infusion, prior to 4th ramucirumab infusion ( ~ week 6 after 1st dose), prior to 7th ramucirumab infusion (~ week 12 after first dose) and 30 - 37 days after last dose of therapy
  • Maximum concentration (Cmin) (ramucirumab + placebo) [ Time Frame: Cycle 4, Day 1 ]
    Prior to (within Pretreatment period) 1st ramucirumab infusion, prior to 4th ramucirumab infusion ( ~ week 6 after 1st dose), prior to 7th ramucirumab infusion (~ week 12 after first dose) and 30 - 37 days after last dose of therapy
Current Other Pre-specified Outcome Measures
 (submitted: July 1, 2014)
Number of Participants With Serious and Other Non-serious Adverse Events (AE) and Who Died [ Time Frame: Baseline up to 103 weeks and within 30 days of last dose of study drug ]
Participants who died or who had clinically significant events defined as serious AEs (SAEs) and other non-serious AEs (regardless of causality). A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Paclitaxel With or Without Ramucirumab (IMC-1211B) in Metastatic Gastric Adenocarcinoma
Official Title  ICMJE A Randomized, Multicenter, Double-Blind, Placebo-Controlled Phase 3 Study of Weekly Paclitaxel With or Without Ramucirumab (IMC-1121B) Drug Product in Patients With Metastatic Gastric Adenocarcinoma, Refractory to or Progressive After First-Line Therapy With Platinum and Fluoropyrimidine
Brief Summary This is a Phase III randomized multicenter double-blind, placebo controlled trial evaluating the safety and efficacy of paclitaxel plus ramucirumab (IMC-1211B) drug product (DP) compared to paclitaxel plus placebo.
Detailed Description

The aim of this study is to determine if paclitaxel given together with ramucirumab (IMC-1211B) as second line therapy will prolong overall survival (OS) compared to paclitaxel alone.

Approximately 663 participants (at least 18 years) in approximately 200 study centers and in approximately 30 countries will be randomized with histologically or cytologically confirmed metastatic gastric or gastroesophageal junction adenocarcinoma. Participants must have received at least one cycle of first line therapy with any platinum/fluoropyrimidine doublet with or without anthracycline (epirubicin or doxorubicin) and must have discontinued this therapy prior to study entry due to disease progression.

Upon registration and completion of screening procedure and reviewing the Inclusion and Exclusion Criteria eligible participants will be randomized to receive either paclitaxel plus ramucirumab or paclitaxel plus placebo.

Ramucirumab (IMC-1211B) DP/placebo will be administered IV on Days 1 and 15, paclitaxel will be administered IV on Days 1, 8 and 15 of a 4 weekly cycle.

Participants will be continuously treated and monitored until radiographic or symptomatic progression of disease, toxicity requiring cessation, protocol noncompliance, or withdrawal of consent.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Gastric Cancer
Intervention  ICMJE
  • Biological: Ramucirumab (IMC-1211B) DP
    8 milligrams/kilogram (mg/kg) intravenous (IV) infusion on Days 1 and 15 of every 4-week cycle
    Other Names:
    • LY3009806
    • IMC-1211B
  • Drug: Placebo
    Ramucirumab placebo IV infusion on Days 1 and 15 of every 4-week cycle
  • Drug: Paclitaxel
    Paclitaxel 80 milligrams per square meter (mg/m²) IV infusion on Days 1, 8, and 15 of every 4-week cycle
Study Arms  ICMJE
  • Experimental: Ramucirumab (IMC-1211B) Drug Product (DP) and Paclitaxel
    Ramucirumab (IMC-1211B) DP and Paclitaxel
    Interventions:
    • Biological: Ramucirumab (IMC-1211B) DP
    • Drug: Paclitaxel
  • Placebo Comparator: Placebo and Paclitaxel
    Placebo and Paclitaxel
    Interventions:
    • Drug: Placebo
    • Drug: Paclitaxel
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 1, 2012)
665
Original Estimated Enrollment  ICMJE
 (submitted: July 26, 2010)
663
Actual Study Completion Date  ICMJE February 2017
Actual Primary Completion Date July 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Signed informed consent
  • histologically or cytologically confirmed gastric or gastroesophageal junction adenocarcinoma
  • Metastatic disease or locally advanced, unresectable disease
  • Disease progression during or within 4 months after the last dose of the first-line therapy (platinum/fluoropyrimidine doublet with or without anthracycline)
  • Organs are functioning well (liver, kidney, blood)
  • Good performance status Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 to 1

Exclusion Criteria:

  • First line chemotherapy for metastatic gastric cancer other than platinum/fluoropyrimidine doublet with or without anthracycline
  • Previous systemic therapy with other anti-angiogenic drugs
  • Uncontrolled high blood pressure
  • Symptomatic or poorly controlled heart disease or had a heart attack or stroke within the last 6 month
  • Evidence of central nervous system (CNS) metastasis at baseline
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Belgium,   Brazil,   Bulgaria,   Chile,   Estonia,   France,   Germany,   Hungary,   Israel,   Italy,   Japan,   Korea, Republic of,   Lithuania,   Mexico,   Poland,   Portugal,   Romania,   Russian Federation,   Singapore,   Spain,   Taiwan,   United Kingdom,   United States
Removed Location Countries Hong Kong
 
Administrative Information
NCT Number  ICMJE NCT01170663
Other Study ID Numbers  ICMJE 13894
I4T-IE-JVBE ( Other Identifier: Eli Lilly and Company )
CP12-0922 ( Other Identifier: ImClone Systems )
2010-020426-18 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
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
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: 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/
Responsible Party Eli Lilly and Company
Study Sponsor  ICMJE Eli Lilly and Company
Collaborators  ICMJE Not Provided
Investigators  ICMJE
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
PRS Account Eli Lilly and Company
Verification Date September 2019

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