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

Gastric Adenocarcinoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02898077
• Other study ID #: 15244
• Secondary ID: I4T-CR-JVCR
• Status: Completed
• Phase: Phase 3
• Start date: March 2, 2017
• Est. completion date: April 12, 2021

Study information

• Verified date: May 2022
• 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 evaluate the efficacy of the study drug known as ramucirumab in participants with gastric and gastroesophageal cancer.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 440
• Est. completion date: April 12, 2021
• Est. primary completion date: June 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Adenocarcinoma
• Esophageal Neoplasms
• Gastric Adenocarcinoma
• Gastroesophageal Junction Adenocarcinoma

Intervention

Drug:
• Ramucirumab
Administered IV
• Paclitaxel
Administered IV
• Placebo
Administered IV

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing
China	The Fifth Medical Center of PLA General Hospital	Beijing	Beijing
China	Jilin Province Tumor Hospital	Chang Chun	Ji Lin
China	Hunan Cancer Hospital	Changsha	Hunan
China	Fujian Medical University Union Hospital	Fuzhou	Fujian
China	Guangdong Provincial People's Hospital	Guangzhou	Guangdong
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong
China	Sir Run Run Shaw Hospital	Hangzhou	Zhejiang
China	The Second Affiliated Hospital of Zhejiang University School of Medicine	Hangzhou	Zhejiang
China	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang
China	Nan Jing No. 81 Hospital	Nan Jing	Jiang Su
China	Jiangsu Cancer Hospital	Nanjing	Jiangsu
China	Nanjing Drum Tower Hosp Affiliated Hosp of Nanjing Univ Med	Nanjing	Jiangsu
China	Zhongshan Hospital, Fudan University	Shanghai	Shanghai
China	The First Hospital of China Medical University	Shenyang	Liaoning
China	Tianjin Medical University Cancer Institute & Hospital	Tianjin
China	Wuhan Union (Xiehe) Hospital	Wuhan	Hubei
China	Wu Han Tongji Hospital	Wuhan City	Hubei
China	Tang Du Hospital, The Second Teaching Hospital of FMMU	Xi'an	Shanxi
China	First hospital affiliated to Zhengzhou University	Zhengzhou	Henan
Malaysia	Advanced Medical & Dental Institute HUSM	Kepala Batas, Pulau Pinang
Malaysia	Hospital Kuala Lumpur	Kuala Lumpur
Malaysia	University Malaya Medical Centre	Kuala Lumpur
Malaysia	Hospital Umum Sarawak	Kuching	Sarawak
Malaysia	National Cancer Institute	Wilayah Persekutuan
Philippines	Dr. Pablo O. Torre Memorial Hospital	Bacolod
Philippines	De La Salle Health Sciences Institute	Cavite City
Philippines	Cebu Doctors Hospital	Cebu City	Cebu
Thailand	King Chulalongkorn Memoiral Hospsital	Bangkok
Thailand	Police General Hospital	Bangkok
Thailand	Rajavithi Hospital	Bangkok	Ratchathewi District
Thailand	Khon Kaen Hospital	Muang, Khon Kaen

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

China,  Malaysia,  Philippines,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Randomization to the Date of the First Radiographically Documented Progressive Disease or Death from Any Cause (Up To 30 Months)
Primary	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.	Randomization to Date of Death from Any Cause (Up To 37 Months)
Secondary	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).	Randomization to the Date of the First Radiographically Documented Progressive Disease (Up To 30 Months)
Secondary	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.	Randomization to Objective Disease Progression (Up To 30 Months)
Secondary	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.	Date of Objective Response to the Date of the First Radiographically Documented Progressive Disease or Death Due to Any Cause (Up To 24 Months)
Secondary	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.	Baseline, 30 Days After Treatment Discontinuation (Up To 20 Months)
Secondary	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.	Baseline, 30 Days After Treatment Discontinuation (Up To 20 Months)
Secondary	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.	Baseline, 30 Days After Treatment Discontinuation (Up To 20 Months)
Secondary	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).	Baseline, 30 Days After Treatment Discontinuation (Up To 20 Months)