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NCT02314117: RAINFALL

A Study of Ramucirumab (LY3009806) in Combination With Capecitabine and Cisplatin in Participants With Stomach Cancer

Completed Phase 3 Results posted Last updated 26 August 2021
What this trial tests

Phase 3 trial testing Ramucirumab in Metastatic Gastric Adenocarcinoma in 645 participants. Completed in 14 August 2020.

Timeline
20 January 2015
Primary endpoint
17 January 2017
14 August 2020

Quick facts

Lead sponsorEli Lilly and Company
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment645
Start date20 January 2015
Primary completion17 January 2017
Estimated completion14 August 2020
Sites135 locations across Italy, Finland, Japan, Poland, Denmark, Netherlands, Russia, Belgium

Drugs / interventions tested

Conditions studied

Sponsor

Eli Lilly and Company — full company profile →

Who can join

18 and older, any sex, with Metastatic 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) Primary · Randomization to Radiological Disease Progression or Death from Any Cause (Up to 26 Months)

PFS time was measured from the date of randomization to the date of radiographic(rgr) documentation of progression(by RECIST v.1.1) or the date of death due to any cause, whichever was earlier.If a participant did not have a complete baseline tumor assessment,then the PFS time was censored at the randomization date.If a participant was not known to have died or have rgr documented progression as of the data cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date. If death or progressive disease(PD) occurred after 2 or more consecutive missing rgr visi

GroupValue95% CI
Ramucirumab + Cisplatin + Capecitabine5.725.45 – 6.51
Placebo + Cisplatin + Capecitabine5.394.47 – 5.72
Overall Survival (OS) Secondary · Randomization to Death from Any Cause (Up To 30 Months)

OS was time from the date of randomization to the date of death from any cause. If the participant was alive at the cutoff for analysis (or was lost to follow-up), OS data were censored for analysis on the last date the participant was known to be alive.

GroupValue95% CI
Ramucirumab + Cisplatin + Capecitabine11.179.92 – 11.93
Placebo + Cisplatin + Capecitabine10.749.53 – 11.89
Progression- Free Survival 2 (PFS2) Secondary · Randomization to Second Radiological or Symptomatic Disease Progression After the Start of Additional Systemic Anticancer Treatment or Death from Any Cause (Up To 26 Months)

PFS2 was defined as the time from the date of randomization to second disease progression (defined as objective radiological or symptomatic progression), or death of any cause, whichever occurs first. Participants alive and for whom a second disease progression has not been observed (including participants who did not receive any additional systemic anticancer treatments) were censored at the last time known to be alive and without second disease progression. The second progression refers to disease progression on or after additional systemic anticancer therapy, regardless if any earlier progr

GroupValue95% CI
Ramucirumab + Cisplatin + Capecitabine10.189.03 – 10.84
Placebo + Cisplatin + Capecitabine9.208.34 – 9.99
Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate [ORR]) Secondary · Randomization to Disease Progression (Up To 26 Months)

Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST v1.1).Target lesions - CR: Disappearance of all lesions; any pathological lymph nodes must have reduction in short axis to \<10 mm. PR: At least a 30% decrease in the sum of diameters of lesions vs the baseline sum. 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 - CR: Disappearance of all lesions and normalization of tumor marker levels; all lymph

GroupValue95% CI
Ramucirumab + Cisplatin + Capecitabine41.135.8 – 46.4
Placebo + Cisplatin + Capecitabine36.431.1 – 41.6
Percentage of Participants With Complete Response (CR), Partial Response (PR) or Stable Disease (SD) (Disease Control Rate [DCR]) Secondary · Randomization to Disease Progression (Up To 26 Months)

DCR was the percentage of participants with a best overall response of CR, PR, or SD as per Response using RECIST v1.1 criteria. Target lesions - CR: Disappearance of all lesions; any pathological lymph nodes must have reduction in short axis to \<10 mm. PR: At least a 30% decrease in the sum of diameters of lesions vs the baseline sum. 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). Stable Disease: Neither sufficient shrin

GroupValue95% CI
Ramucirumab + Cisplatin + Capecitabine81.977.7 – 86.1
Placebo + Cisplatin + Capecitabine76.571.8 – 81.1
Time to Progression (TTP) Secondary · Randomization to Disease Progression (Up To 24 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).

GroupValue95% CI
Ramucirumab + Cisplatin + Capecitabine6.775.88 – 7.66
Placebo + Cisplatin + Capecitabine5.785.55 – 6.37
Duration of Response (DoR) Secondary · Date of Complete Response (CR) or Partial Response (PR) to Date of Objective Disease Progression or Death Due to Any Cause (Up To 26 Months)

Participants achieved an objective response if they had a best overall response of CR or PR.Target lesions- CR:Disappearance of all lesions;any pathological lymph nodes must have reduction in short axis to \<10 mm.PR: At least a 30% decrease in the sum of diameters of lesions vs the baseline sum.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 - CR: Disappearance of all lesions and normalization of tumour marker levels;all lymph

GroupValue95% CI
Ramucirumab + Cisplatin + Capecitabine5.725.09 – 6.34
Placebo + Cisplatin + Capecitabine4.273.88 – 4.90
Time to Deterioration in Quality of Life (QoL) on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) - Global Health Status/ QoL Scale Secondary · Randomization, First worsening in QoL (Up To 26 Months)

Time to sustained deterioration was defined as time from randomization to first worsening in QoL with no subsequent non-worsened assessment. Worsening in global health status/QoL was defined as a decrease of ≥10 points on a 100-point scale. If a participant did not report worsening, time to sustained deterioration was censored at date of last non-worsened assessment.

GroupValue95% CI
Ramucirumab + Cisplatin + Capecitabine9.008.08 – 12.58
Placebo + Cisplatin + Capecitabine9.466.74 – 11.99
Change in Health Status on the EuroQol 5-Dimensions 5-Level Instrument (EQ-5D- 5L) Secondary · Randomization, 30 Days After Treatment Discontinuation (Up To 5 Months)

The EQ-5D-5L is a standardized instrument for use as a measure of self-reported health status. Five dimensions of health status are each assessed with 5 response options and scored as a composite index which were anchored on a scale of 0 to 1 with a higher score representing better health status. Additionally, current health status was assessed on a visual analogue scale (VAS) ranging from 0 to 100 with a higher score representing better health status.

EQ-5D index
GroupValue95% CI
Ramucirumab + Cisplatin + Capecitabine-0.008± 0.148
Placebo + Cisplatin + Capecitabine-0.010± 0.157
EQ-5D VAS
GroupValue95% CI
Ramucirumab + Cisplatin + Capecitabine0.8± 18.56
Placebo + Cisplatin + Capecitabine1.5± 20.33
Time to Deterioration in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) Secondary · Randomization to ECOG PS ≥2 (Up To 26 Months)

The time from the date of randomization to the first date observing ECOG PS ≥2 (that is, deterioration from baseline status of 0 or 1). Participants without PS deterioration were censored at their last documented assessments of 0 or 1. ECOG Performance Status: 2- Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours, 3 -Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours, 4 -Completely disabled. Cannot carry on any selfcare.Totally confined to bed or chair,5- Dead.

GroupValue95% CI
Ramucirumab + Cisplatin + CapecitabineNA12.2 – NA
Placebo + Cisplatin + CapecitabineNANA – NA
Number of Participants With Anti-Ramucirumab Antibodies Secondary · Predose Cycle 1 through 30 Days After Treatment Discontinuation (Up To 24 Months)

Participants who developed treatment-emergent antibody responses to Ramucirumab postbaseline.

GroupValue95% CI
Ramucirumab + Cisplatin + Capecitabine4
Placebo + Cisplatin + Capecitabine5
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Ramucirumab Secondary · Cycle 1 Day 1: 1 hour (hr) end of infusion (EOI), Cycle 3 Day 1: 1hr EOI, Cycle 9 Day 1: 1 hr EOI

Pharmacokinetics (PK): Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Ramucirumab

Cycle 1, Day 1
GroupValue95% CI
Ramucirumab + Cisplatin + Capecitabine133± 31
Cycle 3, Day 1
GroupValue95% CI
Ramucirumab + Cisplatin + Capecitabine173± 35
Cycle 9, Day 1
GroupValue95% CI
Ramucirumab + Cisplatin + Capecitabine169± 60

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline Up To 5.6 Years. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

LY3009806+Capecitabine+Cisplatin
Serious: 161/323 (50%)
Deaths:
Placebo+Capecitabine+Cisplatin
Serious: 150/315 (48%)
Deaths:

Serious adverse events (202 terms)

ReactionSystemLY3009806+Capecitabine+Cis…Placebo+Capecitabine+Cispl…
VomitingGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Abdominal painGastrointestinal disorders
PyrexiaGeneral disorders
AnaemiaBlood and lymphatic system disorders
Febrile neutropeniaBlood and lymphatic system disorders
Acute kidney injuryRenal and urinary disorders
Gastric perforationGastrointestinal disorders
DehydrationMetabolism and nutrition disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
NeutropeniaBlood and lymphatic system disorders
DysphagiaGastrointestinal disorders
NauseaGastrointestinal disorders
PneumoniaInfections and infestations
General physical health deteriorationGeneral disorders
HyponatraemiaMetabolism and nutrition disorders
Gastric haemorrhageGastrointestinal disorders
SepsisInfections and infestations
Decreased appetiteMetabolism and nutrition disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Deep vein thrombosisVascular disorders
Intestinal obstructionGastrointestinal disorders
StomatitisGastrointestinal disorders
SubileusGastrointestinal disorders
HypokalaemiaMetabolism and nutrition disorders
Other adverse events (51 terms — click to expand)

ReactionSystemLY3009806+Capecitabine+Cis…Placebo+Capecitabine+Cispl…
NauseaGastrointestinal disorders
FatigueGeneral disorders
VomitingGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
AnaemiaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
ConstipationGastrointestinal disorders
Neutrophil count decreasedInvestigations
Palmar-plantar erythrodysaesthesia syndromeSkin and subcutaneous tissue disorders
NeutropeniaBlood and lymphatic system disorders
Platelet count decreasedInvestigations
HypertensionVascular disorders
StomatitisGastrointestinal disorders
ProteinuriaRenal and urinary disorders
Weight decreasedInvestigations
Abdominal painGastrointestinal disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
Oedema peripheralGeneral disorders
HypomagnesaemiaMetabolism and nutrition disorders
AstheniaGeneral disorders
HeadacheNervous system disorders
ThrombocytopeniaBlood and lymphatic system disorders
PyrexiaGeneral disorders
HypokalaemiaMetabolism and nutrition disorders
Peripheral sensory neuropathyNervous system disorders
White blood cell count decreasedInvestigations
DizzinessNervous system disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
HiccupsRespiratory, thoracic and mediastinal disorders
DysgeusiaNervous system disorders
Blood creatinine increasedInvestigations
Back painMusculoskeletal and connective tissue disorders
TinnitusEar and labyrinth disorders
InsomniaPsychiatric disorders
DehydrationMetabolism and nutrition disorders
CoughRespiratory, thoracic and mediastinal disorders
Abdominal pain upperGastrointestinal disorders
DysphagiaGastrointestinal disorders
Mucosal inflammationGeneral disorders
Aspartate aminotransferase increasedInvestigations

Most-reported serious reactions: Vomiting, Diarrhoea, Abdominal pain, Pyrexia, Anaemia, Febrile neutropenia, Acute kidney injury, Gastric perforation.

Data from ClinicalTrials.gov NCT02314117 adverse events section.

Sponsor's own description

The main purpose of this study is to evaluate the efficacy of ramucirumab, which is a targeted antibody, in combination with capecitabine and cisplatin compared to capecitabine and cisplatin alone in participants with stomach cancer.

Publications & conference data

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

  1. Advanced gastric cancer: Current treatment landscape and future perspectives.
    Digklia A, Wagner AD. · · 2016 · cited 422× · PMID 26937129 · DOI 10.3748/wjg.v22.i8.2403
  2. Ramucirumab with cisplatin and fluoropyrimidine as first-line therapy in patients with metastatic gastric or junctional adenocarcinoma (RAINFALL): a double-blind, randomised, placebo-controlled, phase 3 trial.
    Fuchs CS, Shitara K, Di Bartolomeo M, Lonardi S, et al · · 2019 · cited 232× · PMID 30718072 · DOI 10.1016/s1470-2045(18)30791-5
  3. Clinical impact of tumour biology in the management of gastroesophageal cancer.
    Lordick F, Janjigian YY. · · 2016 · cited 119× · PMID 26925958 · DOI 10.1038/nrclinonc.2016.15
  4. Ramucirumab combined with FOLFOX as front-line therapy for advanced esophageal, gastroesophageal junction, or gastric adenocarcinoma: a randomized, double-blind, multicenter Phase II trial.
    Yoon HH, Bendell JC, Braiteh FS, Firdaus I, et al · · 2016 · cited 110× · PMID 27765757 · DOI 10.1093/annonc/mdw423
  5. Targeted and novel therapy in advanced gastric cancer.
    Selim JH, Shaheen S, Sheu WC, Hsueh CT. · · 2019 · cited 66× · PMID 31632839 · DOI 10.1186/s40164-019-0149-6
  6. Current and emerging therapies in unresectable and recurrent gastric cancer.
    Jou E, Rajdev L. · · 2016 · cited 43× · PMID 27239108 · DOI 10.3748/wjg.v22.i20.4812
  7. Molecular-targeted first-line therapy for advanced gastric cancer.
    Song H, Zhu J, Lu D. · · 2016 · cited 42× · PMID 27432490 · DOI 10.1002/14651858.cd011461.pub2
  8. Novel targets in the treatment of advanced gastric cancer: a perspective review.
    Fontana E, Smyth EC. · · 2016 · cited 40× · PMID 26929787 · DOI 10.1177/1758834015616935

Verify or expand the search:

Other trials of Ramucirumab

Trials testing the same drug.

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Other Eli Lilly and Company trials

Trials by the same sponsor.

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Data sources for this page

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/NCT02314117.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing