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

Gastric Cancer Clinical Trial

— RAINBOW  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01170663
• Other study ID #: 13894
• Secondary ID: I4T-IE-JVBECP12-
• Status: Completed
• Phase: Phase 3
• Start date: December 2010
• Est. completion date: February 2017

Study information

• Verified date: September 2019
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 665
• Est. completion date: February 2017
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Gastric Cancer

Intervention

Biological:
• Ramucirumab (IMC-1211B) DP
8 milligrams/kilogram (mg/kg) intravenous (IV) infusion on Days 1 and 15 of every 4-week cycle

Drug:
• Placebo
Ramucirumab placebo IV infusion on Days 1 and 15 of every 4-week cycle
• Paclitaxel
Paclitaxel 80 milligrams per square meter (mg/m²) IV infusion on Days 1, 8, and 15 of every 4-week cycle

Locations

Country	Name	City	State
Argentina	ImClone Investigational Site	Buenos Aires
Argentina	ImClone Investigational Site	Caba
Argentina	ImClone Investigational Site	Rosario
Argentina	ImClone Investigational Site	Santa Fe
Australia	ImClone Investigational Site	Bankstown	New South Wales
Australia	ImClone Investigational Site	Coburg	Victoria
Australia	ImClone Investigational Site	Footscray	Victoria
Australia	ImClone Investigational Site	Frankston	Victoria
Australia	ImClone Investigational Site	Kogarah	New South Wales
Australia	ImClone Investigational Site	Kurralta Park	South Australia
Australia	ImClone Investigational Site	Liverpool	New South Wales
Australia	ImClone Investigational Site	Parkville	Victoria
Australia	ImClone Investigational Site	Southport	Queensland
Australia	ImClone Investigational Site	Wollongong	New South Wales
Austria	ImClone Investigational Site	Graz
Austria	ImClone Investigational Site	Linz
Austria	ImClone Investigational Site	Steyr
Austria	ImClone Investigational Site	Vienna
Belgium	ImClone Investigational Site	Bonheiden
Belgium	ImClone Investigational Site	Brugge
Belgium	ImClone Investigational Site	Brussels
Belgium	ImClone Investigational Site	Brussels
Belgium	ImClone Investigational Site	Edegem
Belgium	ImClone Investigational Site	Leuven
Brazil	ImClone Investigational Site	Belo Horizonte
Brazil	ImClone Investigational Site	Belo Horizonte
Brazil	ImClone Investigational Site	Caxias Do Sul
Brazil	ImClone Investigational Site	Dois Lajeados
Brazil	ImClone Investigational Site	Gavea
Brazil	ImClone Investigational Site	Ijui
Brazil	ImClone Investigational Site	Itajai
Brazil	ImClone Investigational Site	Londrina
Brazil	ImClone Investigational Site	Passo Fundo
Brazil	ImClone Investigational Site	Porto Alegre
Brazil	ImClone Investigational Site	Porto Alegre-Rs
Brazil	ImClone Investigational Site	Ribeirão Preto
Brazil	ImClone Investigational Site	Rio De Janeiro
Brazil	ImClone Investigational Site	Salvador
Brazil	ImClone Investigational Site	Sao Jose Rio Preto
Brazil	ImClone Investigational Site	São Paulo
Brazil	ImClone Investigational Site	São Paulo
Brazil	ImClone Investigational Site	São Paulo
Brazil	ImClone Investigational Site	Sorocaba
Bulgaria	ImClone Investigational Site	Sofia
Bulgaria	ImClone Investigational Site	Varna
Chile	ImClone Investigational Site	Providencia
Chile	ImClone Investigational Site	Vina Del Mar
Estonia	ImClone Investigational Site	Tallinn
Estonia	ImClone Investigational Site	Tallinn
France	ImClone Investigational Site	Besancon
France	ImClone Investigational Site	Brest
France	ImClone Investigational Site	Clermont-Ferrand
France	ImClone Investigational Site	Marseille
France	ImClone Investigational Site	Montbeliard
France	ImClone Investigational Site	Montpellier
France	ImClone Investigational Site	Paris
France	ImClone Investigational Site	Paris
France	ImClone Investigational Site	Paris
France	ImClone Investigational Site	Saint-Etienne
Germany	ImClone Investigational Site	Berlin
Germany	ImClone Investigational Site	Bielefeld
Germany	ImClone Investigational Site	Dresden
Germany	ImClone Investigational Site	Essen
Germany	ImClone Investigational Site	Frankfurt
Germany	ImClone Investigational Site	Hamburg
Germany	ImClone Investigational Site	Heidelberg
Germany	ImClone Investigational Site	Leipzig
Germany	ImClone Investigational Site	Mainz
Germany	ImClone Investigational Site	Munich
Germany	ImClone Investigational Site	Recklinghausen
Germany	ImClone Investigational Site	Tuebingen
Hungary	ImClone Investigational Site	Budapest
Hungary	ImClone Investigational Site	Gyula
Hungary	ImClone Investigational Site	Kaposvar
Hungary	ImClone Investigational Site	Pecs
Hungary	ImClone Investigational Site	Szekesfehervar
Israel	ImClone Investigational Site	Beer Sheva
Israel	ImClone Investigational Site	Haifa
Israel	ImClone Investigational Site	Holon
Israel	ImClone Investigational Site	Jerusalem
Israel	ImClone Investigational Site	Petah Tikva
Israel	ImClone Investigational Site	Tel Hashomer
Israel	ImClone Investigational Site	Tel-Aviv
Italy	ImClone Investigational Site	Ancona
Italy	ImClone Investigational Site	Bari
Italy	ImClone Investigational Site	Bergamo
Italy	ImClone Investigational Site	Catania
Italy	ImClone Investigational Site	Genova
Italy	ImClone Investigational Site	Milano
Italy	ImClone Investigational Site	Padova
Italy	ImClone Investigational Site	Pisa
Italy	ImClone Investigational Site	Torino
Japan	ImClone Investigational Site	Aichi
Japan	ImClone Investigational Site	Chiba
Japan	ImClone Investigational Site	Ehime
Japan	ImClone Investigational Site	Fukuoka
Japan	ImClone Investigational Site	Hokkaido
Japan	ImClone Investigational Site	Kochi
Japan	ImClone Investigational Site	Oita
Japan	ImClone Investigational Site	Osaka
Japan	ImClone Investigational Site	Osaka-Pref
Japan	ImClone Investigational Site	Saitama
Japan	ImClone Investigational Site	Shizuoka
Japan	ImClone Investigational Site	Tochigi
Japan	ImClone Investigational Site	Tokyo
Korea, Republic of	ImClone Investigational Site	Incheon
Korea, Republic of	ImClone Investigational Site	Seongnam-Si
Korea, Republic of	ImClone Investigational Site	Seoul
Korea, Republic of	ImClone Investigational Site	Suwon
Korea, Republic of	ImClone Investigational Site	Suwon-City
Lithuania	ImClone Investigational Site	Kaunas
Lithuania	ImClone Investigational Site	Klaipeda
Mexico	ImClone Investigational Site	Juchitan
Mexico	ImClone Investigational Site	Nuevo Leon
Poland	ImClone Investigational Site	Brzozow
Poland	ImClone Investigational Site	Bydgoszcz
Poland	ImClone Investigational Site	Gdansk
Poland	ImClone Investigational Site	Lodz
Poland	ImClone Investigational Site	Lublin
Poland	ImClone Investigational Site	Poznan
Poland	ImClone Investigational Site	Warsaw
Portugal	ImClone Investigational Site	Aveiro
Portugal	ImClone Investigational Site	Coimbra
Portugal	ImClone Investigational Site	Evora
Portugal	ImClone Investigational Site	Porto
Portugal	ImClone Investigational Site	Santa Maria Da Feira
Romania	ImClone Investigational Site	Baia Mare
Romania	ImClone Investigational Site	Bucharest
Romania	ImClone Investigational Site	Iasi
Romania	ImClone Investigational Site	Targu Mures
Russian Federation	ImClone Investigational Site	Krasnodar
Russian Federation	ImClone Investigational Site	Moscow
Russian Federation	ImClone Investigational Site	Perm
Russian Federation	ImClone Investigational Site	Saint Petersburg
Russian Federation	ImClone Investigational Site	Ufa
Singapore	ImClone Investigational Site	Singapore
Spain	ImClone Investigational Site	Avila
Spain	ImClone Investigational Site	Burgos
Spain	ImClone Investigational Site	Jerez De La Frontera
Spain	ImClone Investigational Site	Madrid
Spain	ImClone Investigational Site	Majadahonda
Spain	ImClone Investigational Site	Palma De Mallorca
Spain	ImClone Investigational Site	Sabadell
Spain	ImClone Investigational Site	Sevilla
Taiwan	ImClone Investigational Site	Changhua
Taiwan	ImClone Investigational Site	Kaohsiung
Taiwan	ImClone Investigational Site	Liouying/Tainan
Taiwan	ImClone Investigational Site	Taichung
Taiwan	ImClone Investigational Site	Tainan
Taiwan	ImClone Investigational Site	Taipei
United Kingdom	ImClone Investigational Site	Guildford	Surrey
United Kingdom	ImClone Investigational Site	Maidstone	Kent
United Kingdom	ImClone Investigational Site	Sutton	Surrey
United Kingdom	ImClone Investigational Site	Wolverhampton	West Midlands
United States	ImClone Investigational Site	Albuquerque	New Mexico
United States	ImClone Investigational Site	Atlanta	Georgia
United States	ImClone Investigational Site	Burbank	California
United States	ImClone Investigational Site	Chattanooga	Tennessee
United States	ImClone Investigational Site	East Orange	New Jersey
United States	ImClone Investigational Site	Honolulu	Hawaii
United States	ImClone Investigational Site	Houston	Texas
United States	ImClone Investigational Site	Jacksonville	Florida
United States	ImClone Investigational Site	Los Angeles	California
United States	ImClone Investigational Site	Miramar	Florida
United States	ImClone Investigational Site	New York	New York
United States	ImClone Investigational Site	San Francisco	California
United States	ImClone Investigational Site	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  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, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants With Serious and Other Non-serious Adverse Events (AE) and Who Died	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.	Baseline up to 103 weeks and within 30 days of last dose of study drug
Primary	Overall Survival Time (OS)	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.	Randomization up to 27.5 months
Secondary	Progression-Free Survival (PFS)	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.	Randomization up to 22.2 months
Secondary	Time to Progressive Disease (TTP)	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.	Baseline up to 22.2 months
Secondary	Best Overall Response (BOR) of Complete Response (CR), Partial Response (PR), Stable Disease (SD) or PD	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.	Randomization up to 22.2 months
Secondary	Percentage of Participants With CR or PR (Objective Response Rate [ORR])	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.	Randomization up to 22.2 months
Secondary	Percentage of Participants With Anti-Ramucirumab Antibodies (Serum Anti-Ramucirumab Antibody Assessment )(Immunogenicity)	Participants who developed treatment-emergent antibody responses to Ramucirumab (IMC-1121B) after baseline.	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
Secondary	Maximum Concentration (Cmax) After First Ramucirumab (IMC-1211B) Infusion		Cycle 1, Day 1, 1 hour post end of infusion (28-day cycles)
Secondary	Cmax After 4th Ramucirumab (IMC-1211B) Infusion		Cycle 2, Day 15 1 hour post end of infusion (28-day cycles)
Secondary	Cmax After 7th Ramucirumab (IMC-1211B) Infusion		Cycle 4, Day 1, 1 hour post end of infusion (28-day cycles)
Secondary	Minimum Concentration (Cmin) Prior to First Ramucirumab (IMC-1211B) Infusion	This outcome measure was included in error as the time point was before ramucirumab (IMC-1211B) was administered. Cmin was not analyzed.	Cycle 1, Day 1 predose (28-day cycles)
Secondary	Cmin Prior to 4th Ramucirumab (IMC-1211B) Infusion		Cycle 2, Day 15 (28-day cycle)
Secondary	Cmin Prior to 7th Ramucirumab (IMC-1211B) Infusion		Cycle 4, Day 1 (28-day cycles)
Secondary	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	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.	Baseline, end of therapy (up to 103 weeks)
Secondary	Change From Baseline to End of Therapy in European Quality of Life Questionnaire-5 Dimension (EuroQol EQ-5D) Index Score	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.	Baseline, end of therapy (up to 103 weeks)