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NCT02514551

A Study of Ramucirumab (LY3009806) in Combination With Paclitaxel in Participants With Gastric Cancer

Completed Phase 2 Results posted Last updated 17 June 2020
What this trial tests

Phase 2 trial testing Ramucirumab in Gastric Adenocarcinoma in 245 participants. Completed in 28 December 2018.

Timeline
12 October 2015
Primary endpoint
27 October 2017
28 December 2018

Quick facts

Lead sponsorEli Lilly and Company
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment245
Start date12 October 2015
Primary completion27 October 2017
Estimated completion28 December 2018
Sites52 locations across Italy, Greece, Ukraine, Belgium, Sweden, Germany, Canada, United States

Drugs / interventions tested

Conditions studied

Sponsor

Eli Lilly and Company — full company profile →

Who can join

18 and older, any sex, with Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Progression Free Survival (PFS) in Ramucirumab 12mg/kg Arm I4T-MC-JVCZ Primary · Randomization to Objective Progressive Disease or Death (Up To 21 Months)

PFS was defined as time from the date of randomization(RD) to date of radiographic documentation of progression(RDP) or the date of death due to any cause, whichever is earlier as defined by RECIST v.1.1. Participants with no tumor progression and no death were censored at date of last adequate radiological assessment (AST) or date of RD(whichever is later).PD is at least a 20% increase in sum of diameters of target lesions,taking as reference the smallest sum on study.In addition to the relative increase of 20%,the sum must also demonstrate an absolute increase of at least 5 mm.The appearance

GroupValue95% CI
I4T-MC-JVCZ: 12mg/kg Ramucirumab + 80 mg/m² Paclitaxel5.424.40 – 6.01
Progression Free Survival (PFS) Ramucirumab 12mg/kg Arm and 8mg/kg Arm in I4T-MC-JVCZ Secondary · Randomization to Objective Progressive Disease or Death (Up To 21 Months)

PFS was defined as time from the date of randomization(RD) to date of radiographic documentation of progression(RDP) or the date of death due to any cause, whichever is earlier as defined by RECIST v.1.1. Participants with no tumor progression and no death were censored at date of last adequate radiological assessment(AST) or date of RD(whichever is later).PD is at least a 20% increase in sum of diameters of target lesions,taking as reference the smallest sum on study.In addition to the relative increase of 20%,the sum must also demonstrate an absolute increase of at least 5 mm.The appearance

GroupValue95% CI
12mg/kg Ramucirumab + 80 mg/m² Paclitaxel5.424.40 – 6.01
8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel5.163.81 – 5.65
Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab in Combination With Paclitaxel Secondary · Cycle(C) 1 Day(D) 1: Prior to Infusion(PTI),1 to 1.5 hours(hrs) after end of Infusion(EOI); C1 D15: 3 days PTI; C2 D1: 3 days PTI; C2 D15: 3 days PTI,1 to 1.5 hrs after EOI; C3 D1 and 15: 3 days PTI; C4 D1: 3 days PTI and 1 to 1.5 hrs after EOI

Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab in Combination with Paclitaxel

Cycle 1 Day 15 (Week 2)
GroupValue95% CI
12mg/kg Ramucirumab + 80 mg/m² Paclitaxel39.2± 43
8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel21.4± 58
Cycle 2 Day 1 (Week 4)
GroupValue95% CI
12mg/kg Ramucirumab + 80 mg/m² Paclitaxel63.6± 40
8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel37.1± 50
Cycle 2 Day 15 (Week 6)
GroupValue95% CI
12mg/kg Ramucirumab + 80 mg/m² Paclitaxel76.7± 42
8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel43.5± 53
Cycle 3 Day 1(Week 8)
GroupValue95% CI
12mg/kg Ramucirumab + 80 mg/m² Paclitaxel91.2± 40
8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel51.5± 55
Cycle 3 Day 15 (Week 10)
GroupValue95% CI
12mg/kg Ramucirumab + 80 mg/m² Paclitaxel99.0± 44
8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel52.9± 56
Cycle 4 Day 1 (Week 12)
GroupValue95% CI
12mg/kg Ramucirumab + 80 mg/m² Paclitaxel101± 55
8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel56.1± 56
Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) (Objective Response Rates [ORR]) Secondary · Baseline to Objective Progressive Disease (Up To 21 Months)

ORR was defined as the percentage of participants who achieved a PR or CR per RECIST v.1.1.CR is the disappearance of all target lesions.Any pathological lymph nodes(whether target or non-target)must have reduction in short axis to\<10mm.Tumor marker results must have normalized.PR is at least a 30% decrease in the sum of diameter of target lesions,taking as reference the baseline sum diameters.ORR is calculated as a total number of participants with CR or PR divided by the total number of participants treated multiplied by 100.

GroupValue95% CI
12mg/kg Ramucirumab + 80 mg/m² Paclitaxel27.6
8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel25.4
Percentage of Participants Who Exhibit Stable Disease (SD) or Confirmed Response (CR) or Partial Response (PR) [Disease Control Rate (DCR)] Secondary · Baseline to Objective Progressive Disease (Up To 21 Months)

DCR is defined as the percentage of participants who achieved CR, PR, or SD per RECIST v.1.1. CR is the disappearance of all target lesions. Any pathological lymph nodes (target or non-target) must have reduction in short axis to \<10 mm.Tumor marker results must have normalized. PR is at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD is at least a 20% increase

GroupValue95% CI
12mg/kg Ramucirumab + 80 mg/m² Paclitaxel78.9
8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel75.4
Number of Participants With Anti-Ramucirumab Antibodies Secondary · Cycle 1 Predose through Follow-up (Up To 24 Months)

Participants who had anti-ramucirumab antibodies at postbaseline.

GroupValue95% CI
12mg/kg Ramucirumab + 80 mg/m² Paclitaxel2
8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel1

Adverse events — posted to ClinicalTrials.gov

Time frame: Up To 40 Months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

12mg/kg Ramucirumab + 80 mg/m² Paclitaxel
Serious: 47/123 (38%)
Deaths: 81/123
8 mg/kg Ramucirumab + 80 mg/m² Paclitaxel
Serious: 32/120 (27%)
Deaths: 76/120

Serious adverse events (92 terms)

ReactionSystem12mg/kg Ramucirumab + 80 m…8 mg/kg Ramucirumab + 80 m…
Neutrophil count decreasedInvestigations
Febrile neutropeniaBlood and lymphatic system disorders
Abdominal painGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
Gastric haemorrhageGastrointestinal disorders
VomitingGastrointestinal disorders
Gastrointestinal haemorrhageGastrointestinal disorders
IleusGastrointestinal disorders
AstheniaGeneral disorders
General physical health deteriorationGeneral disorders
JaundiceHepatobiliary disorders
InfectionInfections and infestations
Blood bilirubin increasedInvestigations
Bone marrow failureBlood and lymphatic system disorders
LeukocytosisBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
Cardiac failureCardiac disorders
Cardiopulmonary failureCardiac disorders
Cardiovascular insufficiencyCardiac disorders
AscitesGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
DysphagiaGastrointestinal disorders
Gastric perforationGastrointestinal disorders
Gastric stenosisGastrointestinal disorders
HaematemesisGastrointestinal disorders
Other adverse events (45 terms — click to expand)

ReactionSystem12mg/kg Ramucirumab + 80 m…8 mg/kg Ramucirumab + 80 m…
FatigueGeneral disorders
AnaemiaBlood and lymphatic system disorders
NauseaGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
Neutrophil count decreasedInvestigations
VomitingGastrointestinal disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
NeutropeniaBlood and lymphatic system disorders
AlopeciaSkin and subcutaneous tissue disorders
HypertensionVascular disorders
ConstipationGastrointestinal disorders
Abdominal painGastrointestinal disorders
Aspartate aminotransferase increasedInvestigations
Peripheral sensory neuropathyNervous system disorders
AstheniaGeneral disorders
StomatitisGastrointestinal disorders
Oedema peripheralGeneral disorders
Neuropathy peripheralNervous system disorders
Alanine aminotransferase increasedInvestigations
Weight decreasedInvestigations
White blood cell count decreasedInvestigations
HypoalbuminaemiaMetabolism and nutrition disorders
CoughRespiratory, thoracic and mediastinal disorders
ParaesthesiaNervous system disorders
Abdominal pain upperGastrointestinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
DysphagiaGastrointestinal disorders
HyperglycaemiaMetabolism and nutrition disorders
MyalgiaMusculoskeletal and connective tissue disorders
DysphoniaRespiratory, thoracic and mediastinal disorders
Blood alkaline phosphatase increasedInvestigations
Back painMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
LeukopeniaBlood and lymphatic system disorders
AscitesGastrointestinal disorders
PyrexiaGeneral disorders
Platelet count decreasedInvestigations
DysgeusiaNervous system disorders
ProteinuriaRenal and urinary disorders

Most-reported serious reactions: Neutrophil count decreased, Febrile neutropenia, Abdominal pain, Anaemia, Gastric haemorrhage, Vomiting, Gastrointestinal haemorrhage, Ileus.

Data from ClinicalTrials.gov NCT02514551 adverse events section.

Sponsor's own description

The main purpose of this study is to evaluate the efficacy of an alternative dose of ramucirumab in combination with paclitaxel in participants with second-line metastatic or locally advanced, unresectable gastric or gastroesophageal junction adenocarcinoma (GEJ).

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Targeted therapy in gastroesophageal cancers: past, present and future.
    Woo J, Cohen SA, Grim JE. · · 2015 · cited 18× · PMID 26510453 · DOI 10.1093/gastro/gov052
  2. Exposure-response relationship for ramucirumab from the randomized, double-blind, phase 3 REVEL trial (docetaxel versus docetaxel plus ramucirumab) in second-line treatment of metastatic non-small cell lung cancer.
    Smit EF, Garon EB, Reck M, Cappuzzo F, et al · · 2018 · cited 17× · PMID 29721850 · DOI 10.1007/s00280-018-3560-5
  3. Exposure-response relationship of ramucirumab in patients with advanced second-line colorectal cancer: exploratory analysis of the RAISE trial.
    Cohn AL, Yoshino T, Heinemann V, Obermannova R, et al · · 2017 · cited 17× · PMID 28744667 · DOI 10.1007/s00280-017-3380-z
  4. Clinical Outcomes for Previously Treated Patients with Advanced Gastric or Gastroesophageal Junction Cancer: A Systematic Literature Review and Meta-Analysis.
    Abderhalden LA, Wu P, Amonkar MM, Lang BM, et al · · 2023 · cited 5× · PMID 37219679 · DOI 10.1007/s12029-023-00932-5
  5. Evaluating Alternative Ramucirumab Doses as a Single Agent or with Paclitaxel in Second-Line Treatment of Locally Advanced or Metastatic Gastric/Gastroesophageal Junction Adenocarcinoma: Results from Two Randomized, Open-Label, Phase II Studies.
    Shah MA, Udrea AA, Bondarenko I, Mansoor W, et al · · 2022 · cited 1× · PMID 35267477 · DOI 10.3390/cancers14051168
  6. PD-038Exposure-Response relationship of second-line ramucirumab in East Asian patients with advanced gastric cancer from RAINBOW, a global, randomized, double-blind, phase 3 study
    Kim T, Yen C, Al-Batran S, Gao L, et al · · 2016

Verify or expand the search:

Other trials of Ramucirumab

Trials testing the same drug.

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Trials by the same sponsor.

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02514551.

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