Clinical trial NCT01170663: A Study of Paclitaxel With or Without Ramucirumab (IMC-1211B) in Metastatic Gastric Adenocarcinoma
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Gastric Cancer
Keywords: Metastatic Adenocarcinoma
Gastric Adenocarcinoma
Gastroesophageal Junction Adenocarcinoma
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2010-07-27
Enrollment: 665
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Overall Survival Time (OS)
timeFrame: Randomization up to 27.5 months
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Randomization up to 22.2 months
measure: Time to Progressive Disease (TTP)
timeFrame: Baseline up to 22.2 months
measure: Best Overall Response (BOR) of Complete Response (CR), Partial Response (PR), Stable Disease (SD) or PD
timeFrame: Randomization up to 22.2 months
measure: Percentage of Participants With CR or PR (Objective Response Rate [ORR])
timeFrame: Randomization up to 22.2 months
measure: Percentage of Participants With Anti-Ramucirumab Antibodies (Serum Anti-Ramucirumab Antibody Assessment )(Immunogenicity)
timeFrame: 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
measure: Maximum Concentration (Cmax) After First Ramucirumab (IMC-1211B) Infusion
timeFrame: Cycle 1, Day 1, 1 hour post end of infusion (28-day cycles)
measure: Cmax After 4th Ramucirumab (IMC-1211B) Infusion
timeFrame: Cycle 2, Day 15 1 hour post end of infusion (28-day cycles)
measure: Cmax After 7th Ramucirumab (IMC-1211B) Infusion
timeFrame: Cycle 4, Day 1, 1 hour post end of infusion (28-day cycles)
measure: Minimum Concentration (Cmin) Prior to First Ramucirumab (IMC-1211B) Infusion
timeFrame: Cycle 1, Day 1 predose (28-day cycles)
measure: Cmin Prior to 4th Ramucirumab (IMC-1211B) Infusion
timeFrame: Cycle 2, Day 15 (28-day cycle)
measure: Cmin Prior to 7th Ramucirumab (IMC-1211B) Infusion
timeFrame: Cycle 4, Day 1 (28-day cycles)
measure: 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
timeFrame: Baseline, end of therapy (up to 103 weeks)
measure: Change From Baseline to End of Therapy in European Quality of Life Questionnaire-5 Dimension (EuroQol EQ-5D) Index Score
timeFrame: Baseline, end of therapy (up to 103 weeks)
Other outcomes:
measure: Number of Participants With Serious and Other Non-serious Adverse Events (AE) and Who Died
timeFrame: Baseline up to 103 weeks and within 30 days of last dose of study drug
Locations:
city: Burbank
country: United States
facility: ImClone Investigational Site
state: California
city: Los Angeles
country: United States
facility: ImClone Investigational Site
state: California
city: San Francisco
country: United States
facility: ImClone Investigational Site
state: California
city: Jacksonville
country: United States
facility: ImClone Investigational Site
state: Florida
city: Miramar
country: United States
facility: ImClone Investigational Site
state: Florida
city: Atlanta
country: United States
facility: ImClone Investigational Site
state: Georgia
city: Honolulu
country: United States
facility: ImClone Investigational Site
state: Hawaii
city: East Orange
country: United States
facility: ImClone Investigational Site
state: New Jersey
city: Albuquerque
country: United States
facility: ImClone Investigational Site
state: New Mexico
city: New York
country: United States
facility: ImClone Investigational Site
state: New York
city: Chattanooga
country: United States
facility: ImClone Investigational Site
state: Tennessee
city: Houston
country: United States
facility: ImClone Investigational Site
state: Texas
city: Seattle
country: United States
facility: ImClone Investigational Site
state: Washington
city: Buenos Aires
country: Argentina
facility: ImClone Investigational Site
city: Caba
country: Argentina
facility: ImClone Investigational Site
city: Rosario
country: Argentina
facility: ImClone Investigational Site
city: Santa Fe
country: Argentina
facility: ImClone Investigational Site
city: Bankstown
country: Australia
facility: ImClone Investigational Site
state: New South Wales
city: Kogarah
country: Australia
facility: ImClone Investigational Site
state: New South Wales
city: Liverpool
country: Australia
facility: ImClone Investigational Site
state: New South Wales
city: Wollongong
country: Australia
facility: ImClone Investigational Site
state: New South Wales
city: Southport
country: Australia
facility: ImClone Investigational Site
state: Queensland
city: Kurralta Park
country: Australia
facility: ImClone Investigational Site
state: South Australia
city: Coburg
country: Australia
facility: ImClone Investigational Site
state: Victoria
city: Footscray
country: Australia
facility: ImClone Investigational Site
state: Victoria
city: Frankston
country: Australia
facility: ImClone Investigational Site
state: Victoria
city: Parkville
country: Australia
facility: ImClone Investigational Site
state: Victoria
city: Graz
country: Austria
facility: ImClone Investigational Site
city: Linz
country: Austria
facility: ImClone Investigational Site
city: Steyr
country: Austria
facility: ImClone Investigational Site
city: Vienna
country: Austria
facility: ImClone Investigational Site
city: Bonheiden
country: Belgium
facility: ImClone Investigational Site
city: Brugge
country: Belgium
facility: ImClone Investigational Site
city: Brussels
country: Belgium
facility: ImClone Investigational Site
city: Brussels
country: Belgium
facility: ImClone Investigational Site
city: Edegem
country: Belgium
facility: ImClone Investigational Site
city: Leuven
country: Belgium
facility: ImClone Investigational Site
city: Belo Horizonte
country: Brazil
facility: ImClone Investigational Site
city: Belo Horizonte
country: Brazil
facility: ImClone Investigational Site
city: Caxias Do Sul
country: Brazil
facility: ImClone Investigational Site
city: Dois Lajeados
country: Brazil
facility: ImClone Investigational Site
city: Gavea
country: Brazil
facility: ImClone Investigational Site
city: Ijui
country: Brazil
facility: ImClone Investigational Site
city: Itajai
country: Brazil
facility: ImClone Investigational Site
city: Londrina
country: Brazil
facility: ImClone Investigational Site
city: Passo Fundo
country: Brazil
facility: ImClone Investigational Site
city: Porto Alegre-Rs
country: Brazil
facility: ImClone Investigational Site
city: Porto Alegre
country: Brazil
facility: ImClone Investigational Site
city: Ribeirão Preto
country: Brazil
facility: ImClone Investigational Site
city: Rio De Janeiro
country: Brazil
facility: ImClone Investigational Site
city: Salvador
country: Brazil
facility: ImClone Investigational Site
city: Sao Jose Rio Preto
country: Brazil
facility: ImClone Investigational Site
city: Sorocaba
country: Brazil
facility: ImClone Investigational Site
city: São Paulo
country: Brazil
facility: ImClone Investigational Site
city: São Paulo
country: Brazil
facility: ImClone Investigational Site
city: São Paulo
country: Brazil
facility: ImClone Investigational Site
city: Sofia
country: Bulgaria
facility: ImClone Investigational Site
city: Varna
country: Bulgaria
facility: ImClone Investigational Site
city: Providencia
country: Chile
facility: ImClone Investigational Site
city: Vina Del Mar
country: Chile
facility: ImClone Investigational Site
city: Tallinn
country: Estonia
facility: ImClone Investigational Site
city: Tallinn
country: Estonia
facility: ImClone Investigational Site
city: Besancon
country: France
facility: ImClone Investigational Site
city: Brest
country: France
facility: ImClone Investigational Site
city: Clermont-Ferrand
country: France
facility: ImClone Investigational Site
city: Marseille
country: France
facility: ImClone Investigational Site
city: Montbeliard
country: France
facility: ImClone Investigational Site
city: Montpellier
country: France
facility: ImClone Investigational Site
city: Paris
country: France
facility: ImClone Investigational Site
city: Paris
country: France
facility: ImClone Investigational Site
city: Paris
country: France
facility: ImClone Investigational Site
city: Saint-Etienne
country: France
facility: ImClone Investigational Site
city: Berlin
country: Germany
facility: ImClone Investigational Site
city: Bielefeld
country: Germany
facility: ImClone Investigational Site
city: Dresden
country: Germany
facility: ImClone Investigational Site
city: Essen
country: Germany
facility: ImClone Investigational Site
city: Frankfurt
country: Germany
facility: ImClone Investigational Site
city: Hamburg
country: Germany
facility: ImClone Investigational Site
city: Heidelberg
country: Germany
facility: ImClone Investigational Site
city: Leipzig
country: Germany
facility: ImClone Investigational Site
city: Mainz
country: Germany
facility: ImClone Investigational Site
city: Munich
country: Germany
facility: ImClone Investigational Site
city: Recklinghausen
country: Germany
facility: ImClone Investigational Site
city: Tuebingen
country: Germany
facility: ImClone Investigational Site
city: Budapest
country: Hungary
facility: ImClone Investigational Site
city: Gyula
country: Hungary
facility: ImClone Investigational Site
city: Kaposvar
country: Hungary
facility: ImClone Investigational Site
city: Pecs
country: Hungary
facility: ImClone Investigational Site
city: Szekesfehervar
country: Hungary
facility: ImClone Investigational Site
city: Beer Sheva
country: Israel
facility: ImClone Investigational Site
city: Haifa
country: Israel
facility: ImClone Investigational Site
city: Holon
country: Israel
facility: ImClone Investigational Site
city: Jerusalem
country: Israel
facility: ImClone Investigational Site
city: Petah Tikva
country: Israel
facility: ImClone Investigational Site
city: Tel Hashomer
country: Israel
facility: ImClone Investigational Site
city: Tel-Aviv
country: Israel
facility: ImClone Investigational Site
city: Ancona
country: Italy
facility: ImClone Investigational Site
city: Bari
country: Italy
facility: ImClone Investigational Site
city: Bergamo
country: Italy
facility: ImClone Investigational Site
city: Catania
country: Italy
facility: ImClone Investigational Site
city: Genova
country: Italy
facility: ImClone Investigational Site
city: Milano
country: Italy
facility: ImClone Investigational Site
city: Padova
country: Italy
facility: ImClone Investigational Site
city: Pisa
country: Italy
facility: ImClone Investigational Site
city: Torino
country: Italy
facility: ImClone Investigational Site
city: Aichi
country: Japan
facility: ImClone Investigational Site
city: Chiba
country: Japan
facility: ImClone Investigational Site
city: Ehime
country: Japan
facility: ImClone Investigational Site
city: Fukuoka
country: Japan
facility: ImClone Investigational Site
city: Hokkaido
country: Japan
facility: ImClone Investigational Site
city: Kochi
country: Japan
facility: ImClone Investigational Site
city: Oita
country: Japan
facility: ImClone Investigational Site
city: Osaka-Pref
country: Japan
facility: ImClone Investigational Site
city: Osaka
country: Japan
facility: ImClone Investigational Site
city: Saitama
country: Japan
facility: ImClone Investigational Site
city: Shizuoka
country: Japan
facility: ImClone Investigational Site
city: Tochigi
country: Japan
facility: ImClone Investigational Site
city: Tokyo
country: Japan
facility: ImClone Investigational Site
city: Incheon
country: Korea, Republic of
facility: ImClone Investigational Site
city: Seongnam-Si
country: Korea, Republic of
facility: ImClone Investigational Site
city: Seoul
country: Korea, Republic of
facility: ImClone Investigational Site
city: Suwon-City
country: Korea, Republic of
facility: ImClone Investigational Site
city: Suwon
country: Korea, Republic of
facility: ImClone Investigational Site
city: Kaunas
country: Lithuania
facility: ImClone Investigational Site
city: Klaipeda
country: Lithuania
facility: ImClone Investigational Site
city: Juchitan
country: Mexico
facility: ImClone Investigational Site
city: Nuevo Leon
country: Mexico
facility: ImClone Investigational Site
city: Brzozow
country: Poland
facility: ImClone Investigational Site
city: Bydgoszcz
country: Poland
facility: ImClone Investigational Site
city: Gdansk
country: Poland
facility: ImClone Investigational Site
city: Lodz
country: Poland
facility: ImClone Investigational Site
city: Lublin
country: Poland
facility: ImClone Investigational Site
city: Poznan
country: Poland
facility: ImClone Investigational Site
city: Warsaw
country: Poland
facility: ImClone Investigational Site
city: Aveiro
country: Portugal
facility: ImClone Investigational Site
city: Coimbra
country: Portugal
facility: ImClone Investigational Site
city: Evora
country: Portugal
facility: ImClone Investigational Site
city: Porto
country: Portugal
facility: ImClone Investigational Site
city: Santa Maria Da Feira
country: Portugal
facility: ImClone Investigational Site
city: Baia Mare
country: Romania
facility: ImClone Investigational Site
city: Bucharest
country: Romania
facility: ImClone Investigational Site
city: Iasi
country: Romania
facility: ImClone Investigational Site
city: Targu Mures
country: Romania
facility: ImClone Investigational Site
city: Krasnodar
country: Russian Federation
facility: ImClone Investigational Site
city: Moscow
country: Russian Federation
facility: ImClone Investigational Site
city: Perm
country: Russian Federation
facility: ImClone Investigational Site
city: Saint Petersburg
country: Russian Federation
facility: ImClone Investigational Site
city: Ufa
country: Russian Federation
facility: ImClone Investigational Site
city: Singapore
country: Singapore
facility: ImClone Investigational Site
city: Avila
country: Spain
facility: ImClone Investigational Site
city: Burgos
country: Spain
facility: ImClone Investigational Site
city: Jerez De La Frontera
country: Spain
facility: ImClone Investigational Site
city: Madrid
country: Spain
facility: ImClone Investigational Site
city: Majadahonda
country: Spain
facility: ImClone Investigational Site
city: Palma De Mallorca
country: Spain
facility: ImClone Investigational Site
city: Sabadell
country: Spain
facility: ImClone Investigational Site
city: Sevilla
country: Spain
facility: ImClone Investigational Site
city: Changhua
country: Taiwan
facility: ImClone Investigational Site
city: Kaohsiung
country: Taiwan
facility: ImClone Investigational Site
city: Liouying/Tainan
country: Taiwan
facility: ImClone Investigational Site
city: Taichung
country: Taiwan
facility: ImClone Investigational Site
city: Tainan
country: Taiwan
facility: ImClone Investigational Site
city: Taipei
country: Taiwan
facility: ImClone Investigational Site
city: Maidstone
country: United Kingdom
facility: ImClone Investigational Site
state: Kent
city: Guildford
country: United Kingdom
facility: ImClone Investigational Site
state: Surrey
city: Sutton
country: United Kingdom
facility: ImClone Investigational Site
state: Surrey
city: Wolverhampton
country: United Kingdom
facility: ImClone Investigational Site
state: West Midlands
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References:
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citation: Yamaguchi K, Shimada Y, Hironaka S, Sugimoto N, Komatsu Y, Nishina T, Omuro Y, Tamura T, Piao Y, Homma G, Jen MH, Liepa AM, Muro K. Quality of Life Associated with Ramucirumab Treatment in Patients with Advanced Gastric Cancer in Japan: Exploratory Analysis from the Phase III RAINBOW Trial. Clin Drug Investig. 2021 Jan;41(1):53-64. doi: 10.1007/s40261-020-00979-3. Epub 2020 Dec 23.
citation: Cascinu S, Bodoky G, Muro K, Van Cutsem E, Oh SC, Folprecht G, Ananda S, Girotto G, Wainberg ZA, Miron MLL, Ajani J, Wei R, Liepa AM, Carlesi R, Emig M, Ohtsu A. Tumor Response and Symptom Palliation from RAINBOW, a Phase III Trial of Ramucirumab Plus Paclitaxel in Previously Treated Advanced Gastric Cancer. Oncologist. 2021 Mar;26(3):e414-e424. doi: 10.1002/onco.13623. Epub 2020 Dec 23.
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citation: Chau I, Fuchs CS, Ohtsu A, Barzi A, Liepa AM, Cui ZL, Hsu Y, Al-Batran SE. Association of quality of life with disease characteristics and treatment outcomes in patients with advanced gastric cancer: Exploratory analysis of RAINBOW and REGARD phase III trials. Eur J Cancer. 2019 Jan;107:115-123. doi: 10.1016/j.ejca.2018.11.013. Epub 2018 Dec 14.
citation: Tabernero J, Ohtsu A, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Ajani JA, Tomasek J, Safran H, Chandrawansa K, Hsu Y, Heathman M, Khan A, Ni L, Melemed AS, Gao L, Ferry D, Fuchs CS. Exposure-Response Analyses of Ramucirumab from Two Randomized, Phase III Trials of Second-line Treatment for Advanced Gastric or Gastroesophageal Junction Cancer. Mol Cancer Ther. 2017 Oct;16(10):2215-2222. doi: 10.1158/1535-7163.MCT-16-0895. Epub 2017 Jul 17.
citation: Al-Batran SE, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov ON, Kim TY, Cunningham D, Rougier P, Muro K, Liepa AM, Chandrawansa K, Emig M, Ohtsu A, Wilke H. Quality-of-life and performance status results from the phase III RAINBOW study of ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated gastric or gastroesophageal junction adenocarcinoma. Ann Oncol. 2016 Apr;27(4):673-9. doi: 10.1093/annonc/mdv625. Epub 2016 Jan 7.
citation: Shitara K, Muro K, Shimada Y, Hironaka S, Sugimoto N, Komatsu Y, Nishina T, Yamaguchi K, Segawa Y, Omuro Y, Tamura T, Doi T, Yukisawa S, Yasui H, Nagashima F, Gotoh M, Esaki T, Emig M, Chandrawansa K, Liepa AM, Wilke H, Ichimiya Y, Ohtsu A. Subgroup analyses of the safety and efficacy of ramucirumab in Japanese and Western patients in RAINBOW: a randomized clinical trial in second-line treatment of gastric cancer. Gastric Cancer. 2016 Jul;19(3):927-38. doi: 10.1007/s10120-015-0559-z. Epub 2015 Oct 28.
citation: Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov O, Kim TY, Cunningham D, Rougier P, Komatsu Y, Ajani J, Emig M, Carlesi R, Ferry D, Chandrawansa K, Schwartz JD, Ohtsu A; RAINBOW Study Group. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1224-35. doi: 10.1016/S1470-2045(14)70420-6. Epub 2014 Sep 17.