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A Study of Ramucirumab in Participants With Gastric, Esophageal, and Gastroesophageal Cancer

Primary Purpose

Stomach Cancer, Esophageal Cancer

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Ramucirumab

Placebo

Oxaliplatin

Leucovorin

5-Fluorouracil

About this trial

This is an interventional treatment trial for Stomach Cancer focused on measuring cancer, stomach, esophagus, gastroesophageal

Eligibility Criteria

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

Inclusion Criteria:

Histologic or cytologic confirmation of adenocarcinoma of the esophagus, gastroesophageal junction (GEJ), or stomach
Metastatic or locally advanced, unresectable disease at time of study entry
Provided signed informed consent and is amenable to compliance with protocol schedules and testing
Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1 at study entry
Adequate renal, hematological, and hepatic function
Measurable or non-measurable disease at the time of study entry
Resolution to Grade less than or equal to 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.0, of all clinically significant toxic effects of prior locoregional therapy, surgery, or other anticancer therapy, except where otherwise mentioned in the eligibility criteria
Eligible participants of reproductive potential (both sexes) must agree to use adequate contraceptive methods (hormonal or barrier methods) during the study period and at least 12 weeks after the last dose of study therapy
Life expectancy of greater than or equal to 3 months
Willingness to provide blood and tissue samples for research purposes. Submission of tumor specimen is mandatory for participation in this study, if a histologic, paraffin-embedded specimen exists (either from a surgical resection or biopsy); submission of paraffin block or a minimum of 8 unstained slides is required if sufficient sample. NOTE: If insufficient additional tissue exists (that is, all tissue has been utilized for prior diagnostic purposes), participation in the study is allowable without the requirement for an additional biopsy; this situation must be discussed with the study principal investigator and/or the ImClone medical monitor or designee.

Exclusion Criteria:

The participant has received prior first-line systemic therapy for advanced/unresectable and/or metastatic disease (prior adjuvant or neo-adjuvant therapy is permitted)
Previous or concurrent malignancy except for basal or squamous cell skin cancer and/or in situ carcinoma of the cervix, or other solid tumors treated curatively and without evidence of recurrence for at least 3 years prior to study entry
Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the participant ineligible for entry into this study
The participant is receiving chronic therapy with nonsteroidal anti-inflammatory agents (NSAIDs; for example, indomethacin, ibuprofen, naproxen, or similar agents) or other antiplatelet agents (for example, clopidogrel, ticlopidine, dipyridamole, anagrelide). Aspirin use at doses up to 325 milligrams per day (mg/day) is permitted.
The participant has significant third-space fluid retention (for example, ascites or pleural effusion), and is not amenable for required repeated drainage
The participant is pregnant or breastfeeding
Uncontrolled intercurrent illness including, but not limited to, active or uncontrolled clinically serious infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled thromboembolic, or hemorrhagic disorder, psychiatric illness/social situations, or other co-morbid systemic illnesses, or other severe concurrent disease
Immunocompromised participants including participants known to be human immunodeficiency virus (HIV) positive.
Progressive disease less than or equal to 12 months of completing platinum or 5-FU treatment, including capecitabine, if given previously in the perioperative (adjuvant or neoadjuvant) setting
Current or recent (within 28 days prior to randomization) treatment with an investigational drug that has not received regulatory approval for any indication at the time of study entry, or participation in another interventional clinical trial. Participants participating in surveys or observational studies are eligible to participate in this study.
Are currently enrolled in, or discontinued within the last 28 days from, a clinical trial involving ramucirumab drug product (DP), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
Received prior therapy with an antiangiogenic agent (including but not limited to bevacizumab, sunitinib, or sorafenib)
Major surgical procedure or significant traumatic injury less than 28 days prior to randomization, or anticipation of need for elective or planned major surgical procedure during the course of the study. Subcutaneous venous access device placement within 7 days prior to randomization
Clinically significant peripheral neuropathy at the time of registration
Known central nervous system metastases that are symptomatic or untreated
New York Heart Association (NYHA) classification III-IV congestive heart failure
Greater than normal risk of bleeding or coagulopathy in the absence of therapeutic anticoagulation; Grade 3/4 gastrointestinal bleeding within 3 months prior to registration; active bleeding (that is, within 14 days prior to first dose of study therapy); or pathological condition present that carries a high risk of bleeding (for example, tumor involving major vessels or known varices)
Participant has experienced any arterial thromboembolic events, including but not limited to myocardial infarction, stroke, transient ischemic attack (TIA), cerebrovascular accident, or unstable angina, less than or equal to 6 months prior to registration
Clinically significant vascular disease (for example, aortic aneurysm, aortic dissection) for which more than minimal intervention is being administered or planned
History of hypertensive crisis or hypertensive encephalopathy or current poorly-controlled hypertension despite standard medical management
History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess less than 6 months prior to registration
Known hypersensitivity to any of the treatment components of modified FOLFOX6 (mFOLFOX6) (oxaliplatin, 5-FU, and leucovorin) or ramucirumab DP

Sites / Locations

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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Ramucirumab

Placebo

Arm Description

Oxaliplatin 85 milligrams per square meter (mg/m^2) given on Day 1 of a 2-week cycle Leucovorin 400 mg/m^2 given on Day 1 of a 2-week cycle 5-Fluorouracil (5-FU) 400 mg/m^2 bolus given on Day 1 of a 2-week cycle 5-FU 2400 mg/m^2 continuously given over 46-48 hours on Day 1 of a 2-week cycle Ramucirumab 8 milligrams per kilogram (mg/kg) given on Day 1 of a 2-week cycle Participants will receive study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion is met

Oxaliplatin 85 mg/m^2 given on Day 1 of a 2-week cycle Leucovorin 400 mg/m^2 given on Day 1 of a 2-week cycle 5-FU 400 mg/m^2 bolus given on Day 1 of a 2-week cycle 5-FU 2400 mg/m^2 continuously given over 46-48 hours on Day 1 of a 2-week cycle Placebo given on Day 1 of a 2-week cycle Participants will receive study treatment every 2 weeks until disease progression, unacceptable toxicity, or another withdrawal criterion is met

Outcomes

Primary Outcome Measures

Progression-Free Survival (PFS)

PFS was defined using Response Evaluation Criteria in Solid Tumors [RECIST version (v.) 1.1] as the time from randomization to the first observation of progressive disease (PD) or death due to any cause, whichever came first. PD was a ≥20% increase in the sum of the diameters of target lesions with the sum demonstrating an absolute increase of ≥5 millimeters (mm); the appearance of ≥1 new lesions or unequivocal progression of non-target lesions. If a participant did not have a baseline disease assessment, PFS time was censored at the randomization date, regardless of whether or not PD or death was observed. Participants not known to have died or have objective PD were censored at the last post-baseline radiological assessment date.

Secondary Outcome Measures

Overall Survival (OS)

OS was defined as the time from randomization to death due to any cause. OS was censored at the date of the last follow-up visit for participants who were alive or lost to follow-up.

Percentage of Participants Achieving an Objective Response (Objective Response Rate)

The percentage of participants who achieved a best overall response of partial response (PR) or complete response (CR) is reported. Response was defined using RECIST, v. 1.1 criteria. CR was the disappearance of all lesions and pathological lymph node reduction in the short axis to <10 mm. PR was a ≥30% decrease in the sum of the diameters of target lesions. The percentage of participants with objective response=(number of participants whose best overall response achieved was CR or PR/number of participants treated)*100.

Duration of Response

Duration of response was defined using RECIST v. 1.1 criteria as the time from the date criteria were met for the first objectively recorded CR or PR until the first date criteria for PD were met or death from any cause. CR was the disappearance of all lesions and pathological lymph node reduction in the short axis to <10 mm. PR was a ≥30% decrease in the sum of the diameters of target lesions. PD was a ≥20% increase in the sum of the diameters of target lesions with the sum demonstrating an absolute increase of ≥5 mm; the appearance of ≥1 new lesions or unequivocal progression of non-target lesions. Participants who were not known to have died and who did not have PD were censored at the date of the last tumor assessment prior to the date of any subsequent systemic anticancer therapy.

Time to Disease Progression (TTP)

TTP was defined using RECIST v. 1.1 as the time from study randomization to the first date of PD. PD was a ≥20% increase in the sum of the diameters of target lesions with the sum demonstrating an absolute increase of ≥5 mm; the appearance of ≥1 new lesions or unequivocal progression of non-target lesions. TTP was censored at the date of last adequate tumor assessment if death was due to causes other than PD.

Number of Participants With Treatment-Emergent Anti-Ramucirumab Antibodies

Participants with treatment-emergent anti-ramucirumab antibodies were participants with a 4-fold increase (2 dilution increase) in immunogenicity titer over baseline titer, or participants who tested negative at baseline and positive post-baseline (at titer of ≥1:20).

Full Information

NCT ID

NCT01246960

First Posted

November 8, 2010

Last Updated

October 3, 2014

Sponsor

Eli Lilly and Company

1. Study Identification

Unique Protocol Identification Number

NCT01246960

Brief Title

A Study of Ramucirumab in Participants With Gastric, Esophageal, and Gastroesophageal Cancer

Official Title

Randomized, Placebo-Controlled, Double-Blind Phase 2 Study of mFOLFOX6 Chemotherapy Plus Ramucirumab Drug Product(IMC-1121B) Versus mFOLFOX6 Plus Placebo for Advanced Adenocarcinoma of the Esophagus, Gastroesophageal Junction or Stomach

Study Type

Interventional

2. Study Status

Record Verification Date

October 2014

Overall Recruitment Status

Completed

Study Start Date

April 2011 (undefined)

Primary Completion Date

September 2013 (Actual)

Study Completion Date

May 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eli Lilly and Company

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study is to determine whether ramucirumab when used in conjunction with chemotherapy treatment can help participants with stomach, esophagus, and gastroesophageal cancer.

6. Conditions and Keywords

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

Stomach Cancer, Esophageal Cancer

Keywords

cancer, stomach, esophagus, gastroesophageal

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

168 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Ramucirumab

Arm Type

Experimental

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Biological

Intervention Name(s)

Ramucirumab

Other Intervention Name(s)

LY3009806, IMC-1121B

Intervention Description

Administered intravenously

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Administered intravenously

Intervention Type

Drug

Intervention Name(s)

Oxaliplatin

Intervention Description

Administered intravenously

Intervention Type

Drug

Intervention Name(s)

Leucovorin

Intervention Description

Administered intravenously

Intervention Type

Drug

Intervention Name(s)

5-Fluorouracil

Other Intervention Name(s)

5-FU

Intervention Description

Administered intravenously

Primary Outcome Measure Information:

Title

Progression-Free Survival (PFS)

Description

Time Frame

Randomization to measured PD or date of death from any cause (up to Month 25.0)

Secondary Outcome Measure Information:

Title

Overall Survival (OS)

Description

OS was defined as the time from randomization to death due to any cause. OS was censored at the date of the last follow-up visit for participants who were alive or lost to follow-up.

Time Frame

Randomization to date of death from any cause (up to Month 28.3)

Title

Percentage of Participants Achieving an Objective Response (Objective Response Rate)

Description

Time Frame

Randomization to measured PD (up to Month 23.0)

Title

Duration of Response

Description

Time Frame

Time of first response to measured PD (up to Month 23.0)

Title

Time to Disease Progression (TTP)

Description

Time Frame

Randomization to measured PD (up to Month 25.0)

Title

Number of Participants With Treatment-Emergent Anti-Ramucirumab Antibodies

Description

Time Frame

Months 1, 2, 4, 6, and 8

Other Pre-specified Outcome Measures:

Title

Number of Participants With Adverse Events (AEs)

Description

Reported are the number of participants who had ramucirumab/placebo-related: AEs, serious AEs (SAEs), AEs based on common terminology criteria for adverse events (CTCAE) ≥Grade 3, AEs = CTCAE Grade 5, as well as, AEs leading to treatment discontinuation and AEs resulting in death. A summary of serious and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.

Time Frame

Baseline through study completion (up to Month 28.3)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Histologic or cytologic confirmation of adenocarcinoma of the esophagus, gastroesophageal junction (GEJ), or stomach Metastatic or locally advanced, unresectable disease at time of study entry Provided signed informed consent and is amenable to compliance with protocol schedules and testing Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1 at study entry Adequate renal, hematological, and hepatic function Measurable or non-measurable disease at the time of study entry Resolution to Grade less than or equal to 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.0, of all clinically significant toxic effects of prior locoregional therapy, surgery, or other anticancer therapy, except where otherwise mentioned in the eligibility criteria Eligible participants of reproductive potential (both sexes) must agree to use adequate contraceptive methods (hormonal or barrier methods) during the study period and at least 12 weeks after the last dose of study therapy Life expectancy of greater than or equal to 3 months Willingness to provide blood and tissue samples for research purposes. Submission of tumor specimen is mandatory for participation in this study, if a histologic, paraffin-embedded specimen exists (either from a surgical resection or biopsy); submission of paraffin block or a minimum of 8 unstained slides is required if sufficient sample. NOTE: If insufficient additional tissue exists (that is, all tissue has been utilized for prior diagnostic purposes), participation in the study is allowable without the requirement for an additional biopsy; this situation must be discussed with the study principal investigator and/or the ImClone medical monitor or designee. Exclusion Criteria: The participant has received prior first-line systemic therapy for advanced/unresectable and/or metastatic disease (prior adjuvant or neo-adjuvant therapy is permitted) Previous or concurrent malignancy except for basal or squamous cell skin cancer and/or in situ carcinoma of the cervix, or other solid tumors treated curatively and without evidence of recurrence for at least 3 years prior to study entry Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the participant ineligible for entry into this study The participant is receiving chronic therapy with nonsteroidal anti-inflammatory agents (NSAIDs; for example, indomethacin, ibuprofen, naproxen, or similar agents) or other antiplatelet agents (for example, clopidogrel, ticlopidine, dipyridamole, anagrelide). Aspirin use at doses up to 325 milligrams per day (mg/day) is permitted. The participant has significant third-space fluid retention (for example, ascites or pleural effusion), and is not amenable for required repeated drainage The participant is pregnant or breastfeeding Uncontrolled intercurrent illness including, but not limited to, active or uncontrolled clinically serious infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled thromboembolic, or hemorrhagic disorder, psychiatric illness/social situations, or other co-morbid systemic illnesses, or other severe concurrent disease Immunocompromised participants including participants known to be human immunodeficiency virus (HIV) positive. Progressive disease less than or equal to 12 months of completing platinum or 5-FU treatment, including capecitabine, if given previously in the perioperative (adjuvant or neoadjuvant) setting Current or recent (within 28 days prior to randomization) treatment with an investigational drug that has not received regulatory approval for any indication at the time of study entry, or participation in another interventional clinical trial. Participants participating in surveys or observational studies are eligible to participate in this study. Are currently enrolled in, or discontinued within the last 28 days from, a clinical trial involving ramucirumab drug product (DP), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study Received prior therapy with an antiangiogenic agent (including but not limited to bevacizumab, sunitinib, or sorafenib) Major surgical procedure or significant traumatic injury less than 28 days prior to randomization, or anticipation of need for elective or planned major surgical procedure during the course of the study. Subcutaneous venous access device placement within 7 days prior to randomization Clinically significant peripheral neuropathy at the time of registration Known central nervous system metastases that are symptomatic or untreated New York Heart Association (NYHA) classification III-IV congestive heart failure Greater than normal risk of bleeding or coagulopathy in the absence of therapeutic anticoagulation; Grade 3/4 gastrointestinal bleeding within 3 months prior to registration; active bleeding (that is, within 14 days prior to first dose of study therapy); or pathological condition present that carries a high risk of bleeding (for example, tumor involving major vessels or known varices) Participant has experienced any arterial thromboembolic events, including but not limited to myocardial infarction, stroke, transient ischemic attack (TIA), cerebrovascular accident, or unstable angina, less than or equal to 6 months prior to registration Clinically significant vascular disease (for example, aortic aneurysm, aortic dissection) for which more than minimal intervention is being administered or planned History of hypertensive crisis or hypertensive encephalopathy or current poorly-controlled hypertension despite standard medical management History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess less than 6 months prior to registration Known hypersensitivity to any of the treatment components of modified FOLFOX6 (mFOLFOX6) (oxaliplatin, 5-FU, and leucovorin) or ramucirumab DP

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

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.

City

Anchorage

State/Province

Alaska

ZIP/Postal Code

99508

Country

United States

Facility Name

City

Scottsdale

State/Province

Arizona

ZIP/Postal Code

85259

Country

United States

Facility Name

City

Alhambra

State/Province

California

ZIP/Postal Code

91801

Country

United States

Facility Name

City

Bakersfield

State/Province

California

ZIP/Postal Code

93309

Country

United States

Facility Name

City

Fullerton

State/Province

California

ZIP/Postal Code

92835

Country

United States

Facility Name

City

Los Angeles

State/Province

California

ZIP/Postal Code

90024

Country

United States

Facility Name

City

Northridge

State/Province

California

ZIP/Postal Code

91325

Country

United States

Facility Name

City

Redondo Beach

State/Province

California

ZIP/Postal Code

90277

Country

United States

Facility Name

City

Santa Barbara

State/Province

California

ZIP/Postal Code

93105

Country

United States

Facility Name

City

Santa Monica

State/Province

California

ZIP/Postal Code

93454

Country

United States

Facility Name

City

Denver

State/Province

Colorado

ZIP/Postal Code

80218

Country

United States

Facility Name

City

Grand Junction

State/Province

Colorado

ZIP/Postal Code

81501

Country

United States

Facility Name

City

Washington

State/Province

District of Columbia

ZIP/Postal Code

20007

Country

United States

Facility Name

City

Englewood

State/Province

Florida

ZIP/Postal Code

34223

Country

United States

Facility Name

City

Pembroke Pines

State/Province

Florida

ZIP/Postal Code

33028

Country

United States

Facility Name

City

West Palm Beach

State/Province

Florida

ZIP/Postal Code

33401

Country

United States

Facility Name

City

Terre Haute

State/Province

Indiana

ZIP/Postal Code

47802

Country

United States

Facility Name

City

Sioux City

State/Province

Iowa

ZIP/Postal Code

51101

Country

United States

Facility Name

City

Wichita

State/Province

Kansas

ZIP/Postal Code

67214

Country

United States

Facility Name

City

New Orleans

State/Province

Louisiana

ZIP/Postal Code

70121

Country

United States

Facility Name

City

Lewiston

State/Province

Maine

ZIP/Postal Code

04240

Country

United States

Facility Name

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21201

Country

United States

Facility Name

City

Burlington

State/Province

Massachusetts

ZIP/Postal Code

01805

Country

United States

Facility Name

City

Springfield

State/Province

Massachusetts

ZIP/Postal Code

01107

Country

United States

Facility Name

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48106

Country

United States

Facility Name

City

Detroit

State/Province

Michigan

ZIP/Postal Code

48201

Country

United States

Facility Name

City

Grand Rapids

State/Province

Michigan

ZIP/Postal Code

49503

Country

United States

Facility Name

City

Kalamazoo

State/Province

Michigan

ZIP/Postal Code

49007

Country

United States

Facility Name

City

Duluth

State/Province

Minnesota

ZIP/Postal Code

55805

Country

United States

Facility Name

City

Rochester

State/Province

Minnesota

ZIP/Postal Code

55905

Country

United States

Facility Name

City

St Louis Park

State/Province

Minnesota

ZIP/Postal Code

55416

Country

United States

Facility Name

City

St Louis

State/Province

Missouri

ZIP/Postal Code

63110

Country

United States

Facility Name

City

Billings

State/Province

Montana

ZIP/Postal Code

59101

Country

United States

Facility Name

City

Bozeman

State/Province

Montana

ZIP/Postal Code

59715

Country

United States

Facility Name

City

Omaha

State/Province

Nebraska

ZIP/Postal Code

68106

Country

United States

Facility Name

City

Las Vegas

State/Province

Nevada

ZIP/Postal Code

89169

Country

United States

Facility Name

City

Hackensack

State/Province

New Jersey

ZIP/Postal Code

07601

Country

United States

Facility Name

City

Bronx

State/Province

New York

ZIP/Postal Code

10467

Country

United States

Facility Name

City

Cincinnati

State/Province

Ohio

ZIP/Postal Code

45242

Country

United States

Facility Name

City

Dayton

State/Province

Ohio

ZIP/Postal Code

45420

Country

United States

Facility Name

City

Oklahoma City

State/Province

Oklahoma

ZIP/Postal Code

73104

Country

United States

Facility Name

City

Danville

State/Province

Pennsylvania

ZIP/Postal Code

17822

Country

United States

Facility Name

City

Dunmore

State/Province

Pennsylvania

ZIP/Postal Code

18512

Country

United States

Facility Name

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19141

Country

United States

Facility Name

City

Charleston

State/Province

South Carolina

ZIP/Postal Code

29425

Country

United States

Facility Name

City

Columbia

State/Province

South Carolina

ZIP/Postal Code

29210

Country

United States

Facility Name

City

Spartanburg

State/Province

South Carolina

ZIP/Postal Code

29303

Country

United States

Facility Name

City

Chattanooga

State/Province

Tennessee

ZIP/Postal Code

37404

Country

United States

Facility Name

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37203

Country

United States

Facility Name

City

Salt Lake City

State/Province

Utah

ZIP/Postal Code

84112

Country

United States

Facility Name

City

Richmond

State/Province

Virginia

ZIP/Postal Code

23230

Country

United States

Facility Name

City

Kirkland

State/Province

Washington

ZIP/Postal Code

98034

Country

United States

Facility Name

City

Mount Vernon

State/Province

Washington

ZIP/Postal Code

98273

Country

United States

Facility Name

City

Seattle

State/Province

Washington

ZIP/Postal Code

98112

Country

United States

Facility Name

City

Tacoma

State/Province

Washington

ZIP/Postal Code

98405

Country

United States

Facility Name

City

Wenatchee

State/Province

Washington

ZIP/Postal Code

98801

Country

United States

Facility Name

City

Madison

State/Province

Wisconsin

ZIP/Postal Code

53792

Country

United States

Facility Name

City

Marshfield

State/Province

Wisconsin

ZIP/Postal Code

54449

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

27765757

Citation

Yoon HH, Bendell JC, Braiteh FS, Firdaus I, Philip PA, Cohn AL, Lewis N, Anderson DM, Arrowsmith E, Schwartz JD, Gao L, Hsu Y, Xu Y, Ferry D, Alberts SR, Wainberg ZA. Ramucirumab combined with FOLFOX as front-line therapy for advanced esophageal, gastroesophageal junction, or gastric adenocarcinoma: a randomized, double-blind, multicenter Phase II trial. Ann Oncol. 2016 Dec;27(12):2196-2203. doi: 10.1093/annonc/mdw423. Epub 2016 Oct 20. Erratum In: Ann Oncol. 2019 Dec 1;30(12):2016.

Results Reference

derived

Learn more about this trial

A Study of Ramucirumab in Participants With Gastric, Esophageal, and Gastroesophageal Cancer

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