A Study of Paclitaxel With or Without Ramucirumab (IMC-1211B) in Metastatic Gastric Adenocarcinoma (RAINBOW)
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| ClinicalTrials.gov Identifier: NCT01170663 |
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Recruitment Status :
Completed
First Posted : July 27, 2010
Results First Posted : July 31, 2014
Last Update Posted : September 18, 2019
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Sponsor:
Eli Lilly and Company
Information provided by (Responsible Party):
Eli Lilly and Company
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Gastric Cancer | Biological: Ramucirumab (IMC-1211B) DP Drug: Placebo Drug: Paclitaxel | Phase 3 |
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 : | Interventional (Clinical Trial) |
| Actual Enrollment : | 665 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | 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 |
| Study Start Date : | December 2010 |
| Actual Primary Completion Date : | July 2013 |
| Actual Study Completion Date : | February 2017 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: Ramucirumab (IMC-1211B) Drug Product (DP) and Paclitaxel
Ramucirumab (IMC-1211B) DP and Paclitaxel
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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:
Drug: Paclitaxel Paclitaxel 80 milligrams per square meter (mg/m²) IV infusion on Days 1, 8, and 15 of every 4-week cycle |
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Placebo Comparator: Placebo and Paclitaxel
Placebo and Paclitaxel
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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 |
Primary Outcome Measures :
- 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.
Secondary Outcome Measures :
- 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.
Other Outcome Measures:
- 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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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
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): NCT01170663
Locations
Show 167 study locations
Sponsors and Collaborators
Eli Lilly and Company
Investigators
| 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 |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Eli Lilly and Company |
| ClinicalTrials.gov Identifier: | NCT01170663 |
| Other Study ID Numbers: |
13894 I4T-IE-JVBE ( Other Identifier: Eli Lilly and Company ) CP12-0922 ( Other Identifier: ImClone Systems ) 2010-020426-18 ( EudraCT Number ) |
| First Posted: | July 27, 2010 Key Record Dates |
| Results First Posted: | July 31, 2014 |
| Last Update Posted: | September 18, 2019 |
| Last Verified: | September 2019 |
| 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/ |
Keywords provided by Eli Lilly and Company:
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Metastatic Adenocarcinoma Gastric Adenocarcinoma Gastroesophageal Junction Adenocarcinoma |
Additional relevant MeSH terms:
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Adenocarcinoma Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Paclitaxel Ramucirumab |
Antineoplastic Agents, Phytogenic Antineoplastic Agents Tubulin Modulators Antimitotic Agents Mitosis Modulators Molecular Mechanisms of Pharmacological Action |