A Study of Ramucirumab in Participants With Gastric or Gastroesophageal Junction Adenocarcinoma

Gastroesophageal Junction Adenocarcinoma Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of S-1 and Oxaliplatin With or Without Ramucirumab as First-line Therapy Followed by Paclitaxel With Ramucirumab as Second-line Therapy in Patients With Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02539225
• Other study ID #: 15461
• Secondary ID: I4T-JE-JVCW
• Status: Completed
• Phase: Phase 2
• Start date: October 5, 2015
• Est. completion date: March 10, 2021

Study information

• Verified date: February 2022
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main purpose of this study is to evaluate the effectiveness of S-1 and oxaliplatin with or without ramucirumab as first line therapy in participants with metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 191
• Est. completion date: March 10, 2021
• Est. primary completion date: October 25, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

• Have a histopathologically or cytologically confirmed diagnosis of metastatic gastric or GEJ adenocarcinoma. Participants with esophageal cancer are not eligible.
• Have not received any prior first-line systemic therapy for gastric or GEJ adenocarcinoma (prior adjuvant or neoadjuvant therapy is permitted). Participants whose disease has progressed after >24 weeks following the last dose of systemic treatment in the adjuvant/neoadjuvant setting are eligible.
• Have measurable or nonmeasurable but evaluable disease determined using guidelines in Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v.1.1).
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale at baseline.
• Have adequate organ function.
• Have an estimated life expectancy of =12 weeks in the judgment of the investigator.
• Eligible participants of reproductive potential (both sexes) must agree to use contraception (hormonal or barrier methods) during the study period and at least 6 months after the last dose of study treatment or longer if required per local regulations.
• Are willing to provide a blood sample for research purposes. Submission of a blood sample is mandatory for participation in this study unless restricted by local regulations or ethical review boards (ERBs); submission of a tumor tissue sample is optional.

Exclusion Criteria:

• Participants with human epidermal growth factor receptor 2 (HER2)-positive status as determined per local standards. Participants with a negative test or having an indeterminate result due to any reason are eligible, provided these participants are not eligible for treatment directed against tumors which overexpress HER2.
• Have radiation therapy within 14 days prior to randomization. Any lesion requiring palliative radiation or which has been previously irradiated cannot be considered for response assessment.
• Have documented brain metastases, leptomeningeal disease, or uncontrolled spinal cord compression.
• Have undergone major surgery within 28 days prior to randomization.
• Are currently enrolled in, or discontinued study drug within the last 28 days from, a clinical trial involving an investigational product or non-approved use of a drug or device (other than the study drug used in this study), or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. Participants participating in surveys or observational studies are eligible to participate in this study.
• Are pregnant or breast feeding. Females of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to first dose of study treatment.
• Have any prior malignancies.
• Have any condition (eg, psychological, geographical, or medical) that does not permit compliance with the study and follow-up procedures or suggest that the participant is, in the investigator's opinion, not an appropriate candidate for the study.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Ramucirumab
Administered IV
• Placebo
Administered IV
• S-1
Administered PO
• Oxaliplatin
Administered IV
• Paclitaxel
Administered IV

Locations

Country	Name	City	State
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Akashi
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Bunkyo-Ku
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Chiba
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Gifu
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kochi
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Koto-ku
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Koto-ku
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kumamoto
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Nagoya
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Nagoya
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Osaka
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Osaka
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Osaka
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Sagamihara
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Sakai
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Sapporo
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Shinjuku-Ku
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Suita-shi
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Takatsuki
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician	Toyonaka
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Utsunomiya
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Yokohama
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Yokohama
Korea, Republic of	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Seoul
Korea, Republic of	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Seoul
Korea, Republic of	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Seoul
Korea, Republic of	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Seoul
Korea, Republic of	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Seoul
Korea, Republic of	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Ulsan-si
Taiwan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Kuei Shan Hsiang
Taiwan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Taichung
Taiwan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Tainan
Taiwan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Taipei
Taiwan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

Japan,  Korea, Republic of,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS)	PFS is defined as the time from the date of randomization until the date of objectively determined progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) or death from any cause, whichever is first. Disease progression is defined as =20% increase in the sum of diameters of target lesions, taking as reference smallest sum on study (included baseline sum if that was the smallest on study); sum must have demonstrated an absolute increase of =5 millimeter (mm) or the appearance of =1 new lesions was progression. Participants who did not progress, were lost to follow-up were censored at the day of their last adequate tumor assessment.	Randomization to Radiographic Documentation of Progression or Death Due to Any Cause (Up to 25 Months)
Secondary	Progression-free Survival to the Second Disease Progression (PFS 2)	Progression-free survival 2 (PFS2) is defined as the time from the date of randomization to second disease progression (defined as the date of first tumor assessment observing PD defined by RECIST v.1.1, after the start of second-line therapy using the last tumor assessment before starting the second-line therapy (RAM+PTX) as the baseline assessment), or death of any cause, whichever occurs first. If the second-line therapy was not started, the OS will be substituted for PFS2. If a post-discontinuation therapy was started before observing PD after the start of second-line therapy. PD is defined as 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. PFS2 will be censored at the date of the last adequate tumor assessment on or before staring the post-discontinuation therapy.	Randomization to Second Radiographic Documentation of Progression or Death Due to Any Cause (Up to 31 Months)
Secondary	Overall Survival (OS)	Overall survival is defined as time from the date of randomization to the date of death from any cause. If the patient was alive at the cut-off for analysis (or lost to follow-up), OS data were censored for analysis on the last date the patient was known to be alive.	Randomization to Death Due to Any Cause (Up to 31 Months)
Secondary	Percentage of Participants With Objective Response Rate (ORR)	The ORR is the number of all participants with Partial Response (PR) or Complete Response (CR) according to RECIST v1.1 from the start of the treatment until disease progression/recurrence. CR is defined as the disappearance of all non-nodal target lesions, with the short axes of any target lymph nodes reduced to <10 mm. PR is defined as =30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph nodes), taking as reference the baseline sum diameter. Disease progression is defined as =20% increase in the sum of diameters of target lesions, taking as reference smallest sum on study (included baseline sum if that was the smallest on study); sum must have demonstrated an absolute increase of =5 mm or the appearance of =1 new lesions was progression.	Randomization to Disease Progression (Up to 25 Months)
Secondary	Disease Control Rate (DCR)	Disease Control Rate (DCR) was the percentage of participants with a best overall response of CR, PR, or Stable Disease (SD) as per Response using RECIST v1.1 criteria. 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. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. Disease progression is defined as =20% increase in the sum of diameters of target lesions, taking as reference smallest sum on study (included baseline sum if that was the smallest on study); sum must have demonstrated an absolute increase of =5 mm or the appearance of =1 new lesions was progression.	Randomization to Disease Progression (Up to 25 Months)
Secondary	Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab in Part A	Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab in Part A.	Cycle 1 Day 1 & 8 Predose, Cycle 2 Day 1 Predose, Cycle 3 Day 1 Predose, Cycle 5 Day 1 Predose, Cycle 9 Day 1 Predose
Secondary	Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab in Part B	Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab in Part B.	Cycle 1 Day 1 predose, Cycle 2 Day 1 predose
Secondary	Number of Participants With Anti-Ramucirumab Antibodies	Participant is considered as treatment emergent anti-drug antibody (TE ADA) positive if the participant has at least one post baseline titer that is a 4-fold or greater increase in titer from baseline measurement. If baseline result is ADA Not Present, then the participant is TE ADA+ if there is at least one post baseline result of ADA Present with titer >= 20.	Baseline through 25 months

External Links

•   A Study of Ramucirumab in Participants With Gastric or Gastroesophageal Junction Adenocarcinoma