Back to results

A Study of Paclitaxel With or Without Ramucirumab (LY3009806) in Participants With Gastric or Gastroesophageal Cancer

Primary Purpose

Gastroesophageal Junction Adenocarcinoma, Gastric Adenocarcinoma

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Ramucirumab

Paclitaxel

Placebo

About this trial

This is an interventional treatment trial for Gastroesophageal Junction Adenocarcinoma focused on measuring Second line, Angiogenesis, Vascular endothelial growth factor receptor 2

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Have an Eastern Cooperative Oncology Group Performance Status (ECOGPS) of 0 or 1 at study entry.
Have a histopathologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction (GEJ) adenocarcinoma.
Have metastatic disease or locally advanced, unresectable disease.
Have at least 1 measurable lesion based on Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1.
Have experienced documented objective radiographic or symptomatic disease progression during first-line therapy, or within 4 months after the last dose of first-line therapy with any platinum/fluoropyrimidine doublet for unresectable or metastatic disease.
Have adequate organ function.
Have urinary protein ≤1+ on dipstick or routine urinalysis.

Exclusion Criteria:

Have undergone major surgery within 28 days prior to randomization.
Have received any first-line chemotherapy other than platinum and fluoropyrimidine with or without anthracycline for advanced gastric or GEJ adenocarcinoma.
Have received any previous systemic therapy (including investigational agents) targeting vascular endothelial growth factor (VEGF) or the VEGF receptor signaling pathways.
Have a history of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism during the 3 months prior to randomization.
Have significant bleeding disorders, vasculitis, or had a significant bleeding episode from the gastrointestinal (GI) tract within 3 months prior to study entry.
Have a history of GI perforation and/or fistulae within 6 months prior to randomization.
Have experienced any arterial thromboembolic event within 6 months prior to randomization.
Have uncontrolled arterial hypertension (systolic blood pressure ≥160 millimeters of mercury [mmHg] or diastolic blood pressure ≥100 mmHg) despite standard medical management.
Have a serious or nonhealing wound, peptic ulcer, or bone fracture within 28 days prior to randomization.
Have a serious illness or medical condition(s).

Sites / Locations

The Fifth Medical Center of PLA General Hospital
Fujian Medical University Union Hospital
Sun Yat-sen University Cancer Center
Guangdong Provincial People's Hospital
Harbin Medical University Cancer Hospital
First hospital affiliated to Zhengzhou University
Wu Han Tongji Hospital
Wuhan Union (Xiehe) Hospital
Hunan Cancer Hospital
Jilin Province Tumor Hospital
Nan Jing No. 81 Hospital
Nanjing Drum Tower Hosp Affiliated Hosp of Nanjing Univ Med
Jiangsu Cancer Hospital
The First Hospital of China Medical University
Zhongshan Hospital, Fudan University
Tang Du Hospital, The Second Teaching Hospital of FMMU
The Second Affiliated Hospital of Zhejiang University School of Medicine
Sir Run Run Shaw Hospital
Beijing Cancer Hospital
Tianjin Medical University Cancer Institute & Hospital
Hospital Umum Sarawak
Advanced Medical & Dental Institute HUSM
Hospital Kuala Lumpur
University Malaya Medical Centre
National Cancer Institute
Cebu Doctors Hospital
Dr. Pablo O. Torre Memorial Hospital
De La Salle Health Sciences Institute
Rajavithi Hospital
King Chulalongkorn Memoiral Hospsital
Police General Hospital
Khon Kaen Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

8 milligram/kilogram (mg/kg) Ramucirumab + 80 mg/square meter (mg/m²) Paclitaxel

Placebo + 80 mg/m² Paclitaxel

Arm Description

8 mg/kg ramucirumab was administered as an intravenous infusion (IV) on days 1 and 15, in combination with 80 mg/m² paclitaxel administered by IV on days 1, 8, and 15 of every 28-day cycle. Participants may continue on treatment until discontinuation criteria were met.

Placebo was administered at a volume equivalent to a dose of 8 mg/kg by IV on Days 1 and 15, in combination with 80 mg/m² paclitaxel administered by IV on Days 1, 8, and 15 of a 28-day cycle. Participants may continue on treatment until discontinuation criteria were met.

Outcomes

Primary Outcome Measures

Progression Free Survival (PFS)

PFS defined as the time from the date of randomization to the first evidence of disease progression as defined by response evaluation criteria in solid tumors (RECIST) v1.1 or death from any cause. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of randomization, regardless of whether or not objectively determined disease progression or death has been observed for the participant. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date.

Overall Survival (OS)

OS defined as the time from randomization to the date of death due to any cause. For each participant who is not known to have died as of the data-inclusion cutoff date for overall survival analysis, OS time was censored on the last date the participant is known to be alive.

Secondary Outcome Measures

Time to Progression (TTP)

TTP was time from the date of randomization to the date of radiographic progression (according to RECIST v.1.1). If a participant died due to any reason without radiographic progression, TTP is censored at the last adequate tumor assessment. Target lesions: Progressive Disease (PD): At least a 20% increase in the sum of diameters of lesions vs the smallest sum on study (the sum must also demonstrate an absolute increase of at least 5 mm); or the appearance of new lesion(s). Non target lesions: PD: Unequivocal progression of existing lesions or the appearance of new lesion(s).

Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])

ORR was the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR 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, and no appearance of new lesions. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

Duration of Objective Response (DoR)

DOR was the time from the date of first evidence of complete response or partial response to the date of objective progression or the date of death due to any cause, whichever is earlier. CR and PR were defined using the RECIST v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. If a responder was not known to have died or have objective progression as of the data inclusion cutoff date, duration of response was censored at the last adequate tumor assessment date. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

Best Change From Baseline on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)

EORTC QLQ-C30 v3.0 was a self-administered questionnaire with multidimensional scales that measures global health status, 5 functional domains (physical, role, cognitive, emotional, and social) and symptom scales of fatigue, pain, nausea and vomiting, dyspnea, loss of appetite, insomnia, constipation, 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, scores range from 0 to 100 with higher scores representing a better level of functioning. For symptoms scales, scores range from 0 to 100 with higher scores representing a greater degree of symptoms. Least square (LS) mean value of changing from baseline to short-term follow up was estimated from the mixed model that was controlled for Treatment, visit, Treatment*Visit and baseline.

Worst Change From Baseline on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)

EORTC QLQ-C30 v3.0 was a self-administered questionnaire with multidimensional scales that measures global health status, 5 functional domains (physical, role, cognitive, emotional, and social) and symptom scales of fatigue, pain, nausea and vomiting, dyspnea, loss of appetite, insomnia, constipation, 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, scores range from 0 to 100 with higher scores representing a better level of functioning. For symptoms scales, scores range from 0 to 100 with higher scores representing a greater degree of symptoms. LS Mean value of changing from baseline to short-term follow up was estimated from the mixed model that was controlled for Treatment, visit, Treatment*Visit and baseline.

Change From Baseline in Participant-Reported European-Quality of Life-5 Dimension Instrument-3 Levels (EQ-5D-3L) Index Score

EQ-5D-3L is a descriptive system of health-related quality of life states consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and each of which has 3 levels of severity (no problems/some or moderate problems/extreme problems) within a particular EQ-5D dimension. A regression equation defines a utility value for these health states to generate an index score. The possible values for index score range from -0.594 (severe problems in all 5 dimensions) to 1 (no problem in all dimensions) on a scale where 1 represents the best possible health state.

Change From Baseline in Participant-Reported EQ-5D-3L Visual Analog Scale (VAS) Score

EQ-5D-3L is a descriptive system of health-related quality of life states consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and each of which has 3 levels of severity (no problems/some or moderate problems/extreme problems) within a particular EQ-5D dimension. The EQ-5D VAS is used to record a participant's rating for his/her current health-related quality of life state on the day of questionnaire administration and is captured on a scale of 0 (worst imaginable health state) to 100 (best imaginable health state).

Full Information

NCT ID

NCT02898077

First Posted

September 8, 2016

Last Updated

May 19, 2022

Sponsor

Eli Lilly and Company

1. Study Identification

Unique Protocol Identification Number

NCT02898077

Brief Title

A Study of Paclitaxel With or Without Ramucirumab (LY3009806) in Participants With Gastric or Gastroesophageal Cancer

Official Title

A Randomized, Multicenter, Double-Blind, Placebo-Controlled, Phase 3 Study of Weekly Paclitaxel With or Without Ramucirumab (IMC-1121B) in Patients With Advanced Gastric or Gastroesophageal Junction Adenocarcinoma, Refractory to or Progressive After First-Line Therapy With Platinum and Fluoropyrimidine

Study Type

Interventional

2. Study Status

Record Verification Date

May 2022

Overall Recruitment Status

Completed

Study Start Date

March 2, 2017 (Actual)

Primary Completion Date

June 30, 2020 (Actual)

Study Completion Date

April 12, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eli Lilly and Company

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy of the study drug known as ramucirumab in participants with gastric and gastroesophageal cancer.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Gastroesophageal Junction Adenocarcinoma, Gastric Adenocarcinoma

Keywords

Second line, Angiogenesis, Vascular endothelial growth factor receptor 2

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

440 (Actual)

8. Arms, Groups, and Interventions

Arm Title

8 milligram/kilogram (mg/kg) Ramucirumab + 80 mg/square meter (mg/m²) Paclitaxel

Arm Type

Experimental

Arm Description

Arm Title

Placebo + 80 mg/m² Paclitaxel

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Ramucirumab

Other Intervention Name(s)

LY3009806

Intervention Description

Administered IV

Intervention Type

Drug

Intervention Name(s)

Paclitaxel

Intervention Description

Administered IV

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Administered IV

Primary Outcome Measure Information:

Title

Progression Free Survival (PFS)

Description

Time Frame

Randomization to the Date of the First Radiographically Documented Progressive Disease or Death from Any Cause (Up To 30 Months)

Title

Overall Survival (OS)

Description

Time Frame

Randomization to Date of Death from Any Cause (Up To 37 Months)

Secondary Outcome Measure Information:

Title

Time to Progression (TTP)

Description

Time Frame

Randomization to the Date of the First Radiographically Documented Progressive Disease (Up To 30 Months)

Title

Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR])

Description

Time Frame

Randomization to Objective Disease Progression (Up To 30 Months)

Title

Duration of Objective Response (DoR)

Description

Time Frame

Date of Objective Response to the Date of the First Radiographically Documented Progressive Disease or Death Due to Any Cause (Up To 24 Months)

Title

Best Change From Baseline on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)

Description

Time Frame

Baseline, 30 Days After Treatment Discontinuation (Up To 20 Months)

Title

Worst Change From Baseline on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)

Description

EORTC QLQ-C30 v3.0 was a self-administered questionnaire with multidimensional scales that measures global health status, 5 functional domains (physical, role, cognitive, emotional, and social) and symptom scales of fatigue, pain, nausea and vomiting, dyspnea, loss of appetite, insomnia, constipation, 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, scores range from 0 to 100 with higher scores representing a better level of functioning. For symptoms scales, scores range from 0 to 100 with higher scores representing a greater degree of symptoms. LS Mean value of changing from baseline to short-term follow up was estimated from the mixed model that was controlled for Treatment, visit, Treatment*Visit and baseline.

Time Frame

Baseline, 30 Days After Treatment Discontinuation (Up To 20 Months)

Title

Change From Baseline in Participant-Reported European-Quality of Life-5 Dimension Instrument-3 Levels (EQ-5D-3L) Index Score

Description

Time Frame

Baseline, 30 Days After Treatment Discontinuation (Up To 20 Months)

Title

Change From Baseline in Participant-Reported EQ-5D-3L Visual Analog Scale (VAS) Score

Description

EQ-5D-3L is a descriptive system of health-related quality of life states consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and each of which has 3 levels of severity (no problems/some or moderate problems/extreme problems) within a particular EQ-5D dimension. The EQ-5D VAS is used to record a participant's rating for his/her current health-related quality of life state on the day of questionnaire administration and is captured on a scale of 0 (worst imaginable health state) to 100 (best imaginable health state).

Time Frame

Baseline, 30 Days After Treatment Discontinuation (Up To 20 Months)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Have an Eastern Cooperative Oncology Group Performance Status (ECOGPS) of 0 or 1 at study entry. Have a histopathologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction (GEJ) adenocarcinoma. Have metastatic disease or locally advanced, unresectable disease. Have at least 1 measurable lesion based on Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1. Have experienced documented objective radiographic or symptomatic disease progression during first-line therapy, or within 4 months after the last dose of first-line therapy with any platinum/fluoropyrimidine doublet for unresectable or metastatic disease. Have adequate organ function. Have urinary protein ≤1+ on dipstick or routine urinalysis. Exclusion Criteria: Have undergone major surgery within 28 days prior to randomization. Have received any first-line chemotherapy other than platinum and fluoropyrimidine with or without anthracycline for advanced gastric or GEJ adenocarcinoma. Have received any previous systemic therapy (including investigational agents) targeting vascular endothelial growth factor (VEGF) or the VEGF receptor signaling pathways. Have a history of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism during the 3 months prior to randomization. Have significant bleeding disorders, vasculitis, or had a significant bleeding episode from the gastrointestinal (GI) tract within 3 months prior to study entry. Have a history of GI perforation and/or fistulae within 6 months prior to randomization. Have experienced any arterial thromboembolic event within 6 months prior to randomization. Have uncontrolled arterial hypertension (systolic blood pressure ≥160 millimeters of mercury [mmHg] or diastolic blood pressure ≥100 mmHg) despite standard medical management. Have a serious or nonhealing wound, peptic ulcer, or bone fracture within 28 days prior to randomization. Have a serious illness or medical condition(s).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

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)

Organizational Affiliation

Eli Lilly and Company

Official's Role

Study Director

Facility Information:

Facility Name

The Fifth Medical Center of PLA General Hospital

City

Beijing

State/Province

Beijing

ZIP/Postal Code

100071

Country

China

Facility Name

Fujian Medical University Union Hospital

City

Fuzhou

State/Province

Fujian

ZIP/Postal Code

350001

Country

China

Facility Name

Sun Yat-sen University Cancer Center

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510060

Country

China

Facility Name

Guangdong Provincial People's Hospital

City

Guangzhou

State/Province

Guangdong

ZIP/Postal Code

510080

Country

China

Facility Name

Harbin Medical University Cancer Hospital

City

Harbin

State/Province

Heilongjiang

ZIP/Postal Code

150081

Country

China

Facility Name

First hospital affiliated to Zhengzhou University

City

Zhengzhou

State/Province

Henan

ZIP/Postal Code

450052

Country

China

Facility Name

Wu Han Tongji Hospital

City

Wuhan City

State/Province

Hubei

ZIP/Postal Code

430030

Country

China

Facility Name

Wuhan Union (Xiehe) Hospital

City

Wuhan

State/Province

Hubei

ZIP/Postal Code

430022

Country

China

Facility Name

Hunan Cancer Hospital

City

Changsha

State/Province

Hunan

ZIP/Postal Code

410013

Country

China

Facility Name

Jilin Province Tumor Hospital

City

Chang Chun

State/Province

Ji Lin

ZIP/Postal Code

130012

Country

China

Facility Name

Nan Jing No. 81 Hospital

City

Nan Jing

State/Province

Jiang Su

ZIP/Postal Code

210002

Country

China

Facility Name

Nanjing Drum Tower Hosp Affiliated Hosp of Nanjing Univ Med

City

Nanjing

State/Province

Jiangsu

ZIP/Postal Code

210008

Country

China

Facility Name

Jiangsu Cancer Hospital

City

Nanjing

State/Province

Jiangsu

ZIP/Postal Code

210009

Country

China

Facility Name

The First Hospital of China Medical University

City

Shenyang

State/Province

Liaoning

ZIP/Postal Code

110001

Country

China

Facility Name

Zhongshan Hospital, Fudan University

City

Shanghai

State/Province

Shanghai

ZIP/Postal Code

200032

Country

China

Facility Name

Tang Du Hospital, The Second Teaching Hospital of FMMU

City

Xi'an

State/Province

Shanxi

ZIP/Postal Code

710038

Country

China

Facility Name

The Second Affiliated Hospital of Zhejiang University School of Medicine

City

Hangzhou

State/Province

Zhejiang

ZIP/Postal Code

310009

Country

China

Facility Name

Sir Run Run Shaw Hospital

City

Hangzhou

State/Province

Zhejiang

ZIP/Postal Code

310016

Country

China

Facility Name

Beijing Cancer Hospital

City

Beijing

ZIP/Postal Code

100142

Country

China

Facility Name

Tianjin Medical University Cancer Institute & Hospital

City

Tianjin

ZIP/Postal Code

300060

Country

China

Facility Name

Hospital Umum Sarawak

City

Kuching

State/Province

Sarawak

ZIP/Postal Code

93586

Country

Malaysia

Facility Name

Advanced Medical & Dental Institute HUSM

City

Kepala Batas, Pulau Pinang

ZIP/Postal Code

13200

Country

Malaysia

Facility Name

Hospital Kuala Lumpur

City

Kuala Lumpur

ZIP/Postal Code

50586

Country

Malaysia

Facility Name

University Malaya Medical Centre

City

Kuala Lumpur

ZIP/Postal Code

59100

Country

Malaysia

Facility Name

National Cancer Institute

City

Wilayah Persekutuan

ZIP/Postal Code

62250

Country

Malaysia

Facility Name

Cebu Doctors Hospital

City

Cebu City

State/Province

Cebu

ZIP/Postal Code

6000

Country

Philippines

Facility Name

Dr. Pablo O. Torre Memorial Hospital

City

Bacolod

ZIP/Postal Code

6100

Country

Philippines

Facility Name

De La Salle Health Sciences Institute

City

Cavite City

ZIP/Postal Code

4114

Country

Philippines

Facility Name

Rajavithi Hospital

City

Bangkok

State/Province

Ratchathewi District

ZIP/Postal Code

10400

Country

Thailand

Facility Name

King Chulalongkorn Memoiral Hospsital

City

Bangkok

ZIP/Postal Code

10330

Country

Thailand

Facility Name

Police General Hospital

City

Bangkok

ZIP/Postal Code

10330

Country

Thailand

Facility Name

Khon Kaen Hospital

City

Muang, Khon Kaen

ZIP/Postal Code

40000

Country

Thailand

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing 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.

IPD Sharing Time Frame

Data are available 6 months after the primary publication and approval of the indication studied in the US and European union (EU), whichever is later. Data will be indefinitely available for requesting.

IPD Sharing Access Criteria

A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.

IPD Sharing URL

https://vivli.org/

Citations:

PubMed Identifier

34626550

Citation

Xu RH, Zhang Y, Pan H, Feng J, Zhang T, Liu T, Qin Y, Qin S, Yin X, Liu B, Ba Y, Yang N, Voon PJ, Tanasanvimon S, Zhou C, Zhang WL, Shen L. Efficacy and safety of weekly paclitaxel with or without ramucirumab as second-line therapy for the treatment of advanced gastric or gastroesophageal junction adenocarcinoma (RAINBOW-Asia): a randomised, multicentre, double-blind, phase 3 trial. Lancet Gastroenterol Hepatol. 2021 Dec;6(12):1015-1024. doi: 10.1016/S2468-1253(21)00313-7. Epub 2021 Oct 7.

Results Reference

derived

Learn more about this trial

A Study of Paclitaxel With or Without Ramucirumab (LY3009806) in Participants With Gastric or Gastroesophageal Cancer

We'll reach out to this number within 24 hrs