Study of IMC-1121B (Ramucirumab) With Best Supportive Care in Participants With Gastric Cancer and Adenocarcinoma

Gastric Cancer Clinical Trial

Official title:

A Phase 3, Randomized, Double-Blinded Study of IMC-1121B and Best Supportive Care (BSC) Versus Placebo and BSC in the Treatment of Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma Following Disease Progression on First-Line Platinum- or Fluoropyrimidine-Containing Combination Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00917384
• Other study ID #: 13893
• Secondary ID: 2008-005964-15CP
• Status: Completed
• Phase: Phase 3
• Start date: August 2009
• Est. completion date: December 2015

Study information

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

Clinical Trial Summary

The purpose of this study is to gather information about the use of an investigational drug called Ramucirumab in adenocarcinomas of the stomach or gastroesophageal junction.

Description:

Placebo-controlled, multicenter Phase 3 study of participants with metastatic gastric cancer [including adenocarcinomas of the gastroesophageal junction (GEJ)] and disease progression on standard first-line chemotherapeutic regimens. Participants will be randomized on a 2:1 basis to receive best supportive care plus ramucirumab administered every 2 weeks or best supportive care plus placebo administered every 2 weeks, respectively. Participants will undergo radiographic assessment of disease status every 6 weeks. Participant will be treated until there is evidence of progressive disease, toxicity requiring cessation, withdrawal of consent, or until other withdrawal criteria are met.

Approximately 348 participants, with histologically- or cytologically-confirmed, metastatic gastric or GEJ adenocarcinoma, and radiographically measurable disease as defined by the Response Evaluation Criteria in Solid Tumors or evaluable, nonmeasurable disease, will be randomized. Participants will be enrolled from approximately 250 study centers in North America, South America, Central America, Asia, Australia, New Zealand, and Europe.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 355
• Est. completion date: December 2015
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed gastric carcinoma, including gastric adenocarcinoma or GEJ adenocarcinoma

• Metastatic disease or locally recurrent, unresectable disease with measurable lymph node metastases

• Measurable disease and/or evaluable disease. Measurable disease is defined as at least one unidimensionally-measurable target lesion [= 2 centimeter (cm) with conventional techniques or = 1 cm by spiral computed tomography (CT)], as defined by Response using Response Evaluation Criteria in Solid Tumors (RECIST).

Examples of evaluable, nonmeasurable disease include gastric, peritoneal, or mesenteric thickening in areas of known disease, or peritoneal nodules that are too small to be considered measurable by RECIST

• Experienced disease progression during or within 4 months after the last dose of first-line therapy for metastatic disease, or during or within 6 months after the last dose of adjuvant therapy

• Disease is not amenable to potentially curative resection

• Participant is = 18 years of age

• Participant has a life expectancy of = 12 weeks

• Participant resolution to Grade = 1 (or to Grade = 2 in the case of neuropathy) by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 3.0, of all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy (with the exception of alopecia)

• Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of 0-1

• The participant has adequate hepatic function as defined by a total bilirubin = 1.5 milligrams/deciliter (mg/dL) [25.65 micromole/liter (µmol/L)], and aspartate transaminase (AST) and alanine transaminase (ALT) = 3.0 x the upper limit of normal (ULN) [or 5.0 x the ULN in the setting of liver metastases]

• The participant has adequate renal function as defined by a serum creatinine = 1.5 x the ULN, or creatinine clearance (measured via 24-hour urine collection) = 40 milliliters/minute (mL/min) (that is, if serum creatinine is > 1.5 x the ULN, a 24-hour urine collection to calculate creatinine clearance must be performed)

• The participant's urinary protein is = 1+ on dipstick or routine urinalysis ([UA]; if urine dipstick or routine analysis is = 2+, a 24-hour urine collection for protein must demonstrate < 1000 milligrams (mg) of protein in 24 hours to allow participation in the study)

• The participant has adequate hematologic function, as evidenced by an absolute neutrophil count (ANC) = 1000 microliters (µL), hemoglobin = 9 grams/deciliter (g/dL) [5.58 millimoles/liter (mmol/L)], and platelets = 100,000/µL

• The participant must have adequate coagulation function as defined by International Normalized Ratio (INR) = 1.5 and a partial thromboplastin time (PTT) = 5 seconds above the ULN (unless receiving anticoagulation therapy). Participant on anticoagulation therapy with unresected primary tumors or local tumor recurrence following resection are not eligible

• If the participant has received prior anthracycline therapy as part of his or her first-line regimen, the participant is able to engage in ordinary physical activity without significant fatigue or dyspnea

• Because the teratogenicity of IMC-1121B is not known, the participant, if sexually active, must be postmenopausal, surgically sterile, or using effective contraception (hormonal or barrier methods)

• Female participant of childbearing potential must have a negative serum pregnancy test within 7 days prior to randomization

• Able to provide informed written consent and is amenable to compliance with protocol schedules and testing

Exclusion Criteria:

• Documented and/or symptomatic brain or leptomeningeal metastases

• Experienced any Grade 3-4 gastrointestinal bleeding within 3 months prior to randomization

• Experienced any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to randomization

• Ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, uncontrolled thrombotic or hemorrhagic disorder, or any other serious uncontrolled medical disorders in the opinion of the investigator

• Ongoing or active psychiatric illness or social situation that would limit compliance with study requirements

• Uncontrolled or poorly-controlled hypertension despite standard medical management

• Participant has a serious or nonhealing wound, ulcer, or bone fracture

• Received chemotherapy, radiotherapy, immunotherapy, or targeted therapy for gastric cancer within 2 weeks prior to randomization

• Received any investigational therapy within 30 days prior to randomization

• Undergone major surgery within 28 days prior to randomization, or subcutaneous venous access device placement within 7 days prior to randomization

• Received prior therapy with an agent that directly inhibits vascular endothelial growth factor (VEGF) or VEGF receptor 2 (R-2) activity (including bevacizumab), or any antiangiogenic agent

• Receiving chronic antiplatelet therapy, including aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs, including ibuprofen, naproxen, and others), dipyridamole or clopidogrel, or similar agents. Once-daily aspirin use [maximum dose 325 milligram/day (mg/day)] is permitted

• Participant has elective or planned major surgery to be performed during the course of the clinical trial

• Participant has a known allergy to any of the treatment components

• Pregnant or lactating

• Known to be positive for infection with the human immunodeficiency virus

• Known alcohol or drug dependency

• Participant has a concurrent active malignancy other than adequately-treated nonmelanomatous skin cancer, other noninvasive carcinoma, or in situ neoplasm. A participant with previous history of malignancy is eligible, provided that he/she has been free of disease for > 3 years

Related Conditions & MeSH terms

• Adenocarcinoma
• Gastric Cancer
• Stomach Neoplasms

Intervention

Biological:
• ramucirumab
Administered via intravenous infusion every 2 weeks at a dose of 8 mg/kg

Drug:
• Placebo
Placebo comparator for ramucirumab 8 mg/kg as intravenous infusion every 2 weeks

Other:
• Best Supportive Care (BSC)
BSC as determined appropriate by the investigator(s). BSC may include but are not limited to antiemetic agents, opiate and nonopiate analgesic agents, appetite stimulants, and granulocyte and erythroid growth factors.

Locations

Country	Name	City	State
Argentina	ImClone Investigational Site	Buenos Aires
Argentina	ImClone Investigational Site	Capital Federal
Argentina	ImClone Investigational Site	Ciudad Autonoma de Buenos Aires
Argentina	ImClone Investigational Site	Ciudada Autonoma
Argentina	ImClone Investigational Site	Cordoba
Argentina	ImClone Investigational Site	Rosario
Australia	ImClone Investigational Site	Bedford Park
Australia	ImClone Investigational Site	East Melbourne	Victoria
Australia	ImClone Investigational Site	Hobart	Tasmania
Australia	ImClone Investigational Site	Perth	Western Australia
Australia	ImClone Investigational Site	St. Leonards
Australia	ImClone Investigational Site	Wodonga	New South Wales
Australia	ImClone Investigational Site	Woodville
Bosnia and Herzegovina	ImClone Investigational Site	Sarajevo
Brazil	ImClone Investigational Site	Barretos
Brazil	ImClone Investigational Site	Belo Horizonte
Brazil	ImClone Investigational Site	Belo Horizonte
Brazil	ImClone Investigational Site	Brasilia
Brazil	ImClone Investigational Site	Curitiba
Brazil	ImClone Investigational Site	Curitiba
Brazil	ImClone Investigational Site	Florianopolis
Brazil	ImClone Investigational Site	Ijui
Brazil	ImClone Investigational Site	Lajeados
Brazil	ImClone Investigational Site	Londrina
Brazil	ImClone Investigational Site	Passo Fundo
Brazil	ImClone Investigational Site	Porto Alegre
Brazil	ImClone Investigational Site	Porto Alegre
Brazil	ImClone Investigational Site	Porto Alegre
Brazil	ImClone Investigational Site	Sao Paulo
Canada	ImClone Investigational Site	Edmonton	Alberta
Canada	ImClone Investigational Site	Montreal	Quebec
Canada	ImClone Investigational Site	Sherbrooke	Quebec
Chile	ImClone Investigational Site	Concepcion
Chile	ImClone Investigational Site	La Serena
Chile	ImClone Investigational Site	Santiago
Colombia	ImClone Investigational Site	Monteria
Croatia	ImClone Investigational Site	Osijek
Croatia	ImClone Investigational Site	Pula
Croatia	ImClone Investigational Site	Slavonski Brod
Croatia	ImClone Investigational Site	Zagreb
Czechia	ImClone Investigational Site	Brno
Czechia	ImClone Investigational Site	Hradec Kralove
Czechia	ImClone Investigational Site	Liberec
Czechia	ImClone Investigational Site	Nova Ves pod Plesi
Czechia	ImClone Investigational Site	Olomouc
Czechia	ImClone Investigational Site	Pardubice
Czechia	ImClone Investigational Site	Prague
Czechia	ImClone Investigational Site	Praha 10
Czechia	ImClone Investigational Site	Praha 2
Czechia	ImClone Investigational Site	Pribram
Egypt	ImClone Investigational Site	Alexandria
Egypt	ImClone Investigational Site	Cairo
Guatemala	ImClone Investigational Site	Guatemala
Guatemala	ImClone Investigational Site	Guatemala
India	ImClone Investigational Site	Bangalore	Karna
India	ImClone Investigational Site	Bangalore	Karna
India	ImClone Investigational Site	Bangalore
India	ImClone Investigational Site	Bhopal	Madh Prad
India	ImClone Investigational Site	Chennai	Tamilnadu
India	ImClone Investigational Site	Chennai	Tamilnadu
India	ImClone Investigational Site	Chennai	Kilpauk
India	ImClone Investigational Site	Chennai
India	ImClone Investigational Site	Cochin	Kerala
India	ImClone Investigational Site	Hyderabad	Andh Prad
India	ImClone Investigational Site	Hyderabad	Andh Prad
India	ImClone Investigational Site	Hyderabad
India	ImClone Investigational Site	Hyderabad
India	ImClone Investigational Site	Indore	Madh Prad
India	ImClone Investigational Site	Kolkata	W Bengal
India	ImClone Investigational Site	Kolkata	W Bengal
India	ImClone Investigational Site	Kolkata
India	ImClone Investigational Site	Mumbai
India	ImClone Investigational Site	Mumbai
India	ImClone Investigational Site	Mumbai	Mahara
India	ImClone Investigational Site	Nashik	Mahara
India	ImClone Investigational Site	New Delhi	Delhi
India	ImClone Investigational Site	Pune	Mahara
India	ImClone Investigational Site	Pune
India	ImClone Investigational Site	Thiruvananthapuram	Kerala
India	ImClone Investigational Site	Trivandrum	Kerala
India	ImClone Investigational Site	West Bengal
Indonesia	ImClone Investigational Site	Jakarta
Indonesia	ImClone Investigational Site	Jakarta
Indonesia	ImClone Investigational Site	Jakarta
Indonesia	ImClone Investigational Site	Sumatera Utara
Indonesia	ImClone Investigational Site	West Java
Italy	ImClone Investigational Site	Aviano
Italy	ImClone Investigational Site	Bologna
Italy	ImClone Investigational Site	Brescia
Italy	ImClone Investigational Site	Cremona
Italy	ImClone Investigational Site	Lido di Camaiore
Italy	ImClone Investigational Site	Lucca
Italy	ImClone Investigational Site	Meldola
Italy	ImClone Investigational Site	Mirano
Italy	ImClone Investigational Site	Noale
Italy	ImClone Investigational Site	Potenza
Italy	ImClone Investigational Site	Rimini
Italy	ImClone Investigational Site	Udine
Korea, Republic of	ImClone Investigational Site	Seoul
Korea, Republic of	ImClone Investigational Site	Seoul
Korea, Republic of	ImClone Investigational Site	Seoul
Korea, Republic of	ImClone Investigational Site	Seoul
Lebanon	ImClone Investigational Site	Beirut
Malta	ImClone Investigational Site	Floriana
Malta	ImClone Investigational Site	Floriana
Mexico	ImClone Investigational Site	Aguascelientes
New Zealand	ImClone Investigational Site	Christchurch
Philippines	ImClone Investigational Site	Cebu City
Philippines	ImClone Investigational Site	Pasig City
Poland	ImClone Investigational Site	Gdansk
Poland	ImClone Investigational Site	Krakow
Poland	ImClone Investigational Site	Olsztyn
Romania	ImClone Investigational Site	Baia Mare
Romania	ImClone Investigational Site	Cluj Napoca
Romania	ImClone Investigational Site	Cluj Napoca
Romania	ImClone Investigational Site	Suceava
Russian Federation	ImClone Investigational Site	Chelyabinsk
Russian Federation	ImClone Investigational Site	Kursk
Russian Federation	ImClone Investigational Site	Moscow
Russian Federation	ImClone Investigational Site	Moscow
Russian Federation	ImClone Investigational Site	Pyatigorsk
Russian Federation	ImClone Investigational Site	St. Petersburg
Russian Federation	ImClone Investigational Site	St. Petersburg
Russian Federation	ImClone Investigational Site	St. Petersburg
South Africa	ImClone Investigational Site	Cape Town
Spain	ImClone Investigational Site	Alcorcon
Spain	ImClone Investigational Site	Barcelona
Spain	ImClone Investigational Site	Barcelona
Spain	ImClone Investigational Site	Elche
Spain	ImClone Investigational Site	Madrid
Spain	ImClone Investigational Site	Santander
Spain	ImClone Investigational Site	Sevilla
Taiwan	ImClone Investigational Site	Kaohsiung
Taiwan	ImClone Investigational Site	Taichung County
Taiwan	ImClone Investigational Site	Taipei
Taiwan	ImClone Investigational Site	Taipei
Thailand	ImClone Investigational Site	Bangkok
Thailand	ImClone Investigational Site	Chiang Mai
Thailand	ImClone Investigational Site	Rajathevee District
Turkey	ImClone Investigational Site	Adana
Turkey	ImClone Investigational Site	Gaziantep
Turkey	ImClone Investigational Site	Istanbul
Turkey	ImClone Investigational Site	Izmir
United Kingdom	ImClone Investigational Site	Bebington	Wirral
United Kingdom	ImClone Investigational Site	London
United Kingdom	ImClone Investigational Site	Sutton
United Kingdom	ImClone Investigational Site	Wolverhampton
United States	ImClone Investigational Site	Bakersfield	California
United States	ImClone Investigational Site	Boston	Massachusetts
United States	ImClone Investigational Site	Charleston	South Carolina
United States	ImClone Investigational Site	Chicago	Illinois
United States	ImClone Investigational Site	Houston	Texas
United States	ImClone Investigational Site	Knoxville	Tennessee
United States	ImClone Investigational Site	La Jolla	California
United States	ImClone Investigational Site	Memphis	Tennessee
United States	ImClone Investigational Site	New Orleans	Louisiana
United States	ImClone Investigational Site	New York	New York
United States	ImClone Investigational Site	Omaha	Nebraska
United States	ImClone Investigational Site	Providence	Rhode Island
United States	ImClone Investigational Site	Redlands	California
United States	ImClone Investigational Site	West Reading	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Bosnia and Herzegovina,  Brazil,  Canada,  Chile,  Colombia,  Croatia,  Czechia,  Egypt,  Guatemala,  India,  Indonesia,  Italy,  Korea, Republic of,  Lebanon,  Malta,  Mexico,  New Zealand,  Philippines,  Poland,  Romania,  Russian Federation,  South Africa,  Spain,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	Overall survival is defined as the time from the date of randomization to the date of death from any cause. Participants who were alive at the date of data cut-off or who were lost to follow-up were censored on the last date the participant was known to be alive	Randomization up to 28 months post-randomization
Secondary	Progression-Free Survival (PFS)	PFS is defined as the time from date of randomization until date of objectively determined progressive disease (PD) or death due to any cause, whichever is first. Participants alive and without PD were censored at the time of last adequate objective tumor assessment (that is, response other than unevaluable).	Randomization up to 17 months
Secondary	Percentage of Participants Who Are Progression-Free at Week 12 (PFS Rate)	The percentage of participants alive and progression-free 12 weeks after randomization. Progression-free survival (PFS) is defined as the time from the date of randomization until the date of objectively determined progressive disease (PD) or death due to any cause whichever comes first. Participants alive and without PD were censored at the time of the last adequate objective tumor assessment.	Week 12 post-randomization
Secondary	Percentage of Participants With Objective Response (Objective Response Rate [ORR])	ORR is equal to the percentage of participants achieving a best overall response of complete response (CR) or partial response (PR). CR and PR were defined using the Response Evaluation Criteria in Solid Tumors (RECIST v1.0). CR is defined as the disappearance of all target and non-target lesions, no appearance of new lesions and confirmed at the consecutive tumor assessment. PR is defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, no appearance of new lesions and confirmed at a subsequent tumor assessment.	Randomization up to 17 months post-randomization
Secondary	Duration of Response (DOR)	DOR is the interval from date of initial documented response (complete response [CR] or partial response [PR]) to first documented date of disease progression (PD) or death as a result of any cause. CR and PR were defined using the Response Evaluation Criteria in Solid Tumors (RECIST v1.0). CR is defined as the disappearance of all target and non-target lesions, no appearance of new lesions and confirmed at the consecutive tumor assessment. PR is defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, no appearance of new lesions and confirmed at a subsequent tumor assessment. Participants who did not relapse or die were censored at the time of the last adequate objective tumor assessment.	Randomization up to 17 months post-randomization
Secondary	Change From Baseline in Quality of Life (QoL) as Measured by the European Organisation for Research and Treatment of Cancer Questionnaire (EORTC-QLQ-C30)	EORTC QLQ-C30 v3.0 is a self-administered questionnaire with multidimensional scales that measures 5 functional domains (physical, role, cognitive, emotional, and social), global health status, and symptom scales of fatigue, pain, nausea and vomiting, dyspnea, loss of appetite, insomnia, constipation and diarrhea, and financial difficulties. A linear transformation is applied to standardize the raw scores to range between 0 and 100 per developer guidelines. For functional domains and global health status, higher scores represent a better level of functioning. For symptoms scales, higher scores represented a greater degree of symptoms. Best change from baseline results determined by Least Square (LS) mean estimated with randomization stratification factors and baseline value as continuous covariate.	Baseline up to Cycle 10 (18 weeks [1 cycle=2 weeks])
Secondary	Number of Participants With Adverse Events	Clinically significant events were defined as serious adverse events (SAE) and other treatment-emergent non-serious adverse events (NSAE). A summary of SAEs and all other NSAEs is located in the Reported Adverse Event module.	Randomization up to 18 months
Secondary	Maximum Concentration (Cmax) of IMC-1121B	Cmax was not analyzed as only pre-dose samples were collected.	6 weeks post-randomization
Secondary	Number of Participants Who Developed Antibodies Against IMC-1121B	The number of participants who developed treatment emergent antibody responses to IMC-1121B after baseline.	Baseline, 12 Weeks