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

• ClinicalTrials.gov Identifier: NCT02898077
• Recruitment Status: Completed
• First Posted: September 13, 2016
• Results First Posted: August 3, 2021
• Last Update Posted: June 14, 2022
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Tracking Information

• First Submitted Date: September 8, 2016
• First Posted Date: September 13, 2016
• Results First Submitted Date: June 10, 2021
• Results First Posted Date: August 3, 2021
• Last Update Posted Date: June 14, 2022
• Actual Study Start Date: March 2, 2017
• Actual Primary Completion Date: June 30, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 12, 2021)

• Progression Free Survival (PFS) [ Time Frame: Randomization to the Date of the First Radiographically Documented Progressive Disease or Death from Any Cause (Up To 30 Months) ]
  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) [ Time Frame: Randomization to Date of Death from Any Cause (Up To 37 Months) ]
  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.

• Original Primary Outcome Measures (submitted: September 8, 2016): Overall Survival (OS) [ Time Frame: Randomization to Date of Death from Any Cause (Approximately 12 Months) ]

Current Secondary Outcome Measures (submitted: July 12, 2021)

• Time to Progression (TTP) [ Time Frame: Randomization to the Date of the First Radiographically Documented Progressive Disease (Up To 30 Months) ]
  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]) [ Time Frame: Randomization to Objective Disease Progression (Up To 30 Months) ]
  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) [ 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) ]
  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) [ Time Frame: Baseline, 30 Days After Treatment Discontinuation (Up To 20 Months) ]
  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) [ Time Frame: Baseline, 30 Days After Treatment Discontinuation (Up To 20 Months) ]
  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 [ Time Frame: Baseline, 30 Days After Treatment Discontinuation (Up To 20 Months) ]
  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 [ Time Frame: Baseline, 30 Days After Treatment Discontinuation (Up To 20 Months) ]
  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).

Original Secondary Outcome Measures (submitted: September 8, 2016)

• Progression Free Survival (PFS) [ Time Frame: Randomization to the Date of the First Radiographically Documented Progressive Disease or Death from Any Cause (Approximately 4 Months) ]
• Time to Progression (TTP) [ Time Frame: Randomization to the Date of the First Radiographically Documented Progressive Disease (Approximately 4 Months) ]
• Objective Response Rate (ORR): Percentage of Participants with a Best Overall Response (BOR) of Partial Response (PR) or Complete Response (CR) [ Time Frame: Randomization to Objective Disease Progression (Approximately 4 Months) ]
• Duration of Objective Response [ Time Frame: Date of Objective Response to the Date of the First Radiographically Documented Progressive Disease or Death Due to Any Cause (Approximately 4 Months) ]
• Change from Baseline on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) [ Time Frame: Baseline, 30 Days After Treatment Discontinuation (Approximately 4 Months) ]
• Change from Baseline on the EuroQol-5 Dimension-3 Level Questionnaire (EQ-5D-3L) [ Time Frame: Baseline, 30 Days After Treatment Discontinuation (Approximately 4 Months) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment

Condition

• Gastroesophageal Junction Adenocarcinoma
• Gastric Adenocarcinoma

Intervention

• Drug: Ramucirumab
  Administered IV
  Other Name: LY3009806
• Drug: Paclitaxel
  Administered IV
• Drug: Placebo
  Administered IV

Study Arms

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

  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.

  Interventions:

  • Drug: Ramucirumab
  • Drug: Paclitaxel
• Experimental: Placebo + 80 mg/m² Paclitaxel

  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.

  Interventions:

  • Drug: Paclitaxel
  • Drug: Placebo

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 12, 2021): 440
• Original Estimated Enrollment (submitted: September 8, 2016): 450
• Actual Study Completion Date: April 12, 2021
• Actual Primary Completion Date: June 30, 2020 (Final data collection date for primary outcome measure)

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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China, Malaysia, Philippines, Thailand

Administrative Information

• NCT Number: NCT02898077
• Other Study ID Numbers: 15244; I4T-CR-JVCR ( Other Identifier: Eli Lilly and Company )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• 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.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• URL: https://vivli.org/

• Current Responsible Party: Eli Lilly and Company
• Original Responsible Party: Same as current
• Current Study Sponsor: Eli Lilly and Company
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: 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); Eli Lilly and Company

• PRS Account: Eli Lilly and Company
• Verification Date: May 2022