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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01170663
First received: July 21, 2010
Last updated: August 29, 2014
Last verified: August 2014
  Purpose

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 Intervention Phase
Gastric Cancer
Biological: Ramucirumab (IMC-1211B) DP
Drug: Placebo
Drug: Paclitaxel
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Overall Survival Time (OS) [ Time Frame: Randomization up to 27.5 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
  • Cmax After 4th Ramucirumab (IMC-1211B) Infusion [ Time Frame: Cycle 2, Day 15 1 hour post end of infusion (28-day cycles) ] [ Designated as safety issue: No ]
  • Cmax After 7th Ramucirumab (IMC-1211B) Infusion [ Time Frame: Cycle 4, Day 1, 1 hour post end of infusion (28-day cycles) ] [ Designated as safety issue: No ]
  • Minimum Concentration (Cmin) Prior to First Ramucirumab (IMC-1211B) Infusion [ Time Frame: Cycle 1, Day 1 predose (28-day cycles) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
  • Cmin Prior to 7th Ramucirumab (IMC-1211B) Infusion [ Time Frame: Cycle 4, Day 1 (28-day cycles) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 665
Study Start Date: December 2010
Estimated Study Completion Date: August 2015
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ramucirumab (IMC-1211B) Drug Product (DP) and Paclitaxel
Ramucirumab (IMC-1211B) DP and Paclitaxel
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: Paclitaxel
Paclitaxel 80 milligrams per square meter (mg/m²) IV infusion on Days 1, 8, and 15 of every 4-week cycle
Placebo Comparator: Placebo and Paclitaxel
Placebo and Paclitaxel
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01170663

  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
  More Information

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01170663     History of Changes
Other Study ID Numbers: 13894, I4T-IE-JVBE, CP12-0922, 2010-020426-18
Study First Received: July 21, 2010
Results First Received: July 1, 2014
Last Updated: August 29, 2014
Health Authority: Argentina: Ministry of Health
Australia: Department of Health and Ageing Therapeutic Goods Administration
Austria: Agency for Health and Food Safety
Belgium: Federal Agency for Medicinal Products and Health Products
Brazil: National Health Surveillance Agency
Bulgaria: Ministry of Health
Chile: Ministry of Health
Estonia: The State Agency of Medicine
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Paul-Ehrlich-Institut
Hong Kong: Department of Health
Hungary: National Institute of Pharmacy
Israel: Ministry of Health
Italy: Ministry of Health
Japan: Pharmaceuticals and Medical Devices Agency
Lithuania: State Medicine Control Agency - Ministry of Health
Mexico: Ministry of Health
Poland: Ministry of Health
Portugal: National Pharmacy and Medicines Institute
Romania: National Medicines Agency
Russia: Ministry of Health of the Russian Federation
Singapore: Health Sciences Authority
South Korea: Korea Food and Drug Administration (KFDA)
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Taiwan: Department of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Keywords provided by Eli Lilly and Company:
Metastatic Adenocarcinoma
Gastric Adenocarcinoma
Gastroesophageal Junction Adenocarcinoma

Additional relevant MeSH terms:
Adenocarcinoma
Stomach Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 30, 2014